Background:Makorin ring finger protein 3 gene(MKRN3)gene mutation is the most common genetic cause of central precocious puberty(CPP)in children.Due to the lack of ideal MKRN3-modified animal model(MKRN3-modified mice...Background:Makorin ring finger protein 3 gene(MKRN3)gene mutation is the most common genetic cause of central precocious puberty(CPP)in children.Due to the lack of ideal MKRN3-modified animal model(MKRN3-modified mice enter puberty only 4–5 days earlier than normal mice),the related research is limited.Methods:Therefore,the MKRN3-modified rabbit was developed using CRISPR(clus-tered regularly interspaced short palindromic repeats)gene editing technology.The genotype identification and phenotype evaluation of MKRN3-modified rabbits were carried out.Results:The first estrus of MKRN3-modified female rabbits was observed~27 days earlier than that of wild-type female rabbits,with a typical CPP phenotype.This study found increased gonadotropin releasing hormone(GnRH)and decreased gonadotropin inhibiting hormone(GnIH)in the hypothalamus of the CPP rabbit model with MKRN3 gene mutation.Although this study failed to fully clarify the pathogenesis of CPP caused by MKRN3 mutation,it found some differentially expressed genes and potential pathways through transcriptome sequencing.Conclusions:This study established a novel CPP model:paternal MKRN3 gene-modified rabbit.It is hoped that the establishment of this model will help researchers better understand,treat,and prevent CPP in the future.展开更多
BACKGROUND At present,the clinical mechanisms underlying precocious puberty remain unclear,making effective intervention for children experiencing this condition and rapidly progressive puberty essential.AIM To explor...BACKGROUND At present,the clinical mechanisms underlying precocious puberty remain unclear,making effective intervention for children experiencing this condition and rapidly progressive puberty essential.AIM To explore the effects of Zhibai dihuang pills and gonadotropin-releasing hormone analogue(GnRHa)on growth and ovarian function in girls with precocious puberty.METHODS The clinical data of 84 adolescent girls with precocious puberty and rapidly progressive puberty from February 2017 to August 2023 were retrospectively analyzed.Girls were divided into a control group and an observation group,with 42 cases in each group.The control group received diet intervention combined with GnRHa treatment,while the observation group received diet intervention combined with Zhibai dihuang pills+GnRHa treatment.Outcomes such as clinical efficacy,growth indicators,ovarian function,and adverse reactions were compared between the two groups.RESULTS The observation group showed superior clinical efficacy compared to the control group(P<0.05).Prior to the intervention,no significant differences were found in growth or ovarian function between the groups(P>0.05).Post-intervention,the observation group exhibited significantly lower rates in growth,height,and bone age,along with reduced levels of progesterone,testosterone,estradiol,prolactin,luteinizing hormone,and follicle-stimulating hormone compared to the control group(P<0.05).The incidence of adverse reactions was similar across both groups(P>0.05).CONCLUSION Combining Zhibai dihuang pills with GnRHa and dietary intervention effectively improves growth,enhances ovarian function,and minimizes adverse reactions in adolescent girls with precocious and rapidly progressive puberty.展开更多
OBJECTIVE:To elucidate the mechanism of the nourishing Yin and purging fire Chinese herbal mixture(NYPF)in delaying light-induced premature puberty in rats.METHODS:Twenty-one days old female SpragueDawley rats were ra...OBJECTIVE:To elucidate the mechanism of the nourishing Yin and purging fire Chinese herbal mixture(NYPF)in delaying light-induced premature puberty in rats.METHODS:Twenty-one days old female SpragueDawley rats were randomly assigned to normal group(N),long light exposure group(L),NYPF and normal saline group(NS).Rats in the L,NYPF and NS groups were exposed to 16 h:350 lux light/8 h:dark,while rats in the N group were exposed to 12 h:50 lux light/12 h:dark.NYPF and normal saline was administered to the rats in the NYPF group or NS group,respectively,from day 21.Five rats in every group were sacrificed at 9 p.m.on day 28(P28),on the day when rat's vulva opened in the L group(L-VO),on the day when the first estrous interphase occurred in rats of L group(L-E1),and on the day when the second estrous interphase occurred in rats of L group(L-E2),respectively.RESULITS:On day 34,all rats in the L group,80%of rats in the NS group,40%of rats in the N group,and 20%of rats in the NYPF group showed complete opening of the vulva.At P28,m RNA level of hypothalamic kisspeptin(Kiss-1)in the L group was significantly higher than that in the N group(P<0.05).The rats in the L and NS groups had significantly lower hypothalamic argininephenylalanine-amide(RFamide)-related peptide 3(RFRP-3)m RNA levels than those in the N group(P<0.05),whereas RFRP-3 m RNA level was significantly higher in the NYPF group than that in the L group(P<0.05).At L-VO,the ovarian index of the L and NS groups was significantly higher than that of the N group(P<0.05)and estradiol(E2)level of the NYPF group was significantly lower than that of the N and NS groups(P<0.05);hypothalamic Kiss-1 m RNA level in the L and NS groups was significantly higher than that in the N and NYPF groups(P<0.05),whereas hypothalamic RFRP-3 m RNA level in the L,NYPF,and NS groups was significantly lower than that in the N group(P<0.05).At L-E1,E2 level of the L and NS groups was significantly higher than that of the N group(P<0.01),whereas it was significantly lower in the NYPF group than that of the N,L,and NS groups(P<0.01),and serum luteinizing hormone level of the L and NS groups was significantly higher than that of the N group(P<0.05);levels of serum melatonin and ovarian melatonin receptor 1(MT-1)m RNA in the L,NYPF,and NS groups were significantly lower than those in the N group(P<0.05).At L-E2,the uterine organ index of the NYPF group was significantly lower than that of the L group(P<0.05);and ovarian MT-1 m RNA level of the L and NS groups was significantly lower than that in the N group(P<0.05).CONCLUSIONS:NYPF can delay puberty onset in rats exposed to strong light for a prolonged duration,and regulation of the gene expression of Kiss-1 and RFRP-3 in the hypothalamus has been suggested as one of the mechanisms.展开更多
Central precocious puberty secondary to Leydig cell tumors is rare in children. We retrospectively analyzed the mid- to long-term follow-up data of patients with Leydig cell tumors. The clinical data of 12 consecutive...Central precocious puberty secondary to Leydig cell tumors is rare in children. We retrospectively analyzed the mid- to long-term follow-up data of patients with Leydig cell tumors. The clinical data of 12 consecutive patients who were treated at Beijing Children’s Hospital, Capital Medical University (Beijing, China), between January 2016 and October 2023 were retrospectively reviewed. Clinical evaluations, including physical examination, hormone examination, serum tumor marker analysis, abdominal and scrotal ultrasound, chest X-ray, and bone age measurement, were conducted before surgery and at follow-up time points. Surgical approaches were selected according to the individual conditions. Patients with an abnormal hormonal status and suspected of having central precocious puberty were referred to endocrinologists to confirm the diagnosis. Subsequently, gonadotropin-releasing hormone analog therapy was proposed. The mean patient age was 81.3 (range: 40–140) months at the time of the operation. Ten patients had peripheral precocious puberty at admission. All patients had elevated preoperative testosterone levels, whereas tumor marker levels were normal. Testis-sparing surgery was performed in eleven patients, and radical orchiectomy was performed in one patient. The follow-up duration (mean ± standard deviation) was 36.2 ± 25.3 months. Five patients had central precocious puberty, with a mean duration of 3.4 (range: 1–6) months postoperatively. Three patients were receiving gonadotropin-releasing hormone analog therapy, and good suppression of puberty was observed. No risk factors were found for secondary central precocious puberty. There was a high prevalence of central precocious puberty secondary to Leydig cell tumors in our study. Gonadotropin-releasing hormone analog therapy has satisfactory treatment effects. Larger sample sizes and long-term follow-up are needed in future studies.展开更多
Background Many phenotypes in animal breeding are derived from incomplete measures,especially if they are challenging or expensive to measure precisely.Examples include time-dependent traits such as reproductive statu...Background Many phenotypes in animal breeding are derived from incomplete measures,especially if they are challenging or expensive to measure precisely.Examples include time-dependent traits such as reproductive status,or lifespan.Incomplete measures for these traits result in phenotypes that are subject to left-,interval-and rightcensoring,where phenotypes are only known to fall below an upper bound,between a lower and upper bound,or above a lower bound respectively.Here we compare three methods for deriving phenotypes from incomplete data using age at first elevation(>1 ng/mL)in blood plasma progesterone(AGEP4),which generally coincides with onset of puberty,as an example trait.Methods We produced AGEP4 phenotypes from three blood samples collected at about 30-day intervals from approximately 5,000 Holstein–Friesian or Holstein–Friesian×Jersey cross-bred dairy heifers managed in 54 seasonal-calving,pasture-based herds in New Zealand.We used these actual data to simulate 7 different visit scenarios,increasing the extent of censoring by disregarding data from one or two of the three visits.Three methods for deriving phenotypes from these data were explored:1)ordinal categorical variables which were analysed using categorical threshold analysis;2)continuous variables,with a penalty of 31 d assigned to right-censored phenotypes;and 3)continuous variables,sampled from within a lower and upper bound using a data augmentation approach.Results Credibility intervals for heritability estimations overlapped across all methods and visit scenarios,but estimated heritabilities tended to be higher when left censoring was reduced.For sires with at least 5 daughters,the correlations between estimated breeding values(EBVs)from our three-visit scenario and each reduced data scenario varied by method,ranging from 0.65 to 0.95.The estimated breed effects also varied by method,but breed differences were smaller as phenotype censoring increased.Conclusion Our results indicate that using some methods,phenotypes derived from one observation per offspring for a time-dependent trait such as AGEP4 may provide comparable sire rankings to three observations per offspring.This has implications for the design of large-scale phenotyping initiatives where animal breeders aim to estimate variance parameters and estimated breeding values(EBVs)for phenotypes that are challenging to measure or prohibitively expensive.展开更多
Background: Hypothalamic hamartoma is a rare non-neoplastic lesion, typically identified in early childhood during investigations for precocious puberty and/or gelastic seizures. However, cases of diagnosis even earli...Background: Hypothalamic hamartoma is a rare non-neoplastic lesion, typically identified in early childhood during investigations for precocious puberty and/or gelastic seizures. However, cases of diagnosis even earlier or during fetal development have been documented. Case Presentation: A newborn girl was diagnosed with hydrocephalus during pregnancy. An MRI revealed a large oval hypothalamic process, which suggested a hypothalamic hamartoma. At the age of 2, she experienced alternating crying and laughing seizures, followed by a decrease in visual acuity. Due to involvement of the optic pathways, surgery was not performed and she underwent antiepileptic medicines and gamma knife radiotherapy. At the age of 5 years and 3 months, she presented with breast development and laboratory tests confirmed central precocious puberty. Quarterly injections of GnRH agonists have since been administered with favorable results. Conclusion: Early-diagnosed hypothalamic hamartomas require close monitoring, by an experienced multidisciplinary, to promptly detect and treat potential complications, especially precocious puberty, and prevent any undesirable impact on final height.展开更多
Objective:This study aimed to evaluate the therapeutic effects of leuprolide acetate extended-release microspheres for injection in children with pediatric precocious puberty.Methods:A total of 110 cases of pediatric ...Objective:This study aimed to evaluate the therapeutic effects of leuprolide acetate extended-release microspheres for injection in children with pediatric precocious puberty.Methods:A total of 110 cases of pediatric precocious puberty admitted between January 2019 and December 2021 were selected and randomized into two groups using a random number table,with 55 cases in the control group and 55 cases in the experimental group.The control group received conventional treatment,while the experimental group was treated with leuprolide acetate extended-release microspheres for injection.The therapeutic effects were observed,and changes in sex hormone levels,ovarian volume,growth indices,and the incidence of adverse reactions were statistically compared between the groups.Results:The experimental group demonstrated superior outcomes in terms of sex hormone levels,ovarian volume,and growth indices compared to the control group.Additionally,the incidence of adverse reactions in the experimental group was significantly lower(P<0.05).Conclusion:The application of leuprolide acetate extended-release microspheres for the treatment of pediatric precocious puberty is associated with improved therapeutic effects and higher safety.展开更多
Puberty is a pivotal biological process that completes sexual maturation to achieve full reproductive capability.It is a major transformational period of life,whose timing is strongly affected by genetic makeup of the...Puberty is a pivotal biological process that completes sexual maturation to achieve full reproductive capability.It is a major transformational period of life,whose timing is strongly affected by genetic makeup of the individual,along with various internal and external factors.Although the exact mechanism for initiation of the cascade of molecular events that culminate in puberty is not yet known,the process of pubertal onset involves interaction of numerous complex signaling pathways of hypothalamopituitary-testicular(HPT)axis.We developed a classification of the mechanisms involved in male puberty that allowed placing many genes into physiological context.These include(i)hypothalamic development during embryogenesis,(ii)synaptogenesis where gonadotropin releasing hormone(GnRH)neurons form neuronal connections with suprahypothalamic neurons,(iii)maintenance of neuron homeostasis,(iv)regulation of synthesis and secretion of GnRH,(v)appropriate receptors/proteins on neurons governing GnRH production and release,(vi)signaling molecules activated by the receptors,(vii)the synthesis and release of GnRH,(viii)the production and release of gonadotropins,(ix)testicular development,(x)synthesis and release of steroid hormones from testes,and(xi)the action of steroid hormones in downstream effector tissues.Defects in components of this system during embryonic development,childhood/adolescence,or adulthood may disrupt/nullify puberty,leading to long-term male infertility and/or hypogonadism.This review provides a list of 598 genes involved in the development of HPT axis and classified according to this schema.Furthermore,this review identifies a subset of 75 genes for which genetic mutations are reported to delay or disrupt male puberty.展开更多
In boys, central precocious puberty （CPP） is the appearance of secondary sex characteristics driven by pituitary gonadotropin secretion before the age of 9 years. In the last years, relevant improvements in the trea...In boys, central precocious puberty （CPP） is the appearance of secondary sex characteristics driven by pituitary gonadotropin secretion before the age of 9 years. In the last years, relevant improvements in the treatment of CPP have been achieved. Because CPP is rare in boys, the majority of papers on this issue focus on girls and do not address specific features of male patients regarding end results and safety. In the present paper, recent advances of CPP management with GnRH analogs in men are summarized. End results in untreated and treated patients are also reviewed by an analysis of the recently published literature on treatment of CPP in men. The available data indicate that therapy with GnRH analogs can improve final height into the range of target height without significant adverse short-term and long-term effects, but longer follow-up of larger series of patients is still required to draw definitive conclusions.展开更多
OBJECTIVE: To evaluate the effect of ZiYin Xiehuo granules(ZYXH) and Zishen Qinggan granules(ZSQG) on partial precocious puberty(PPP).METHODS: This was a multicenter, randomized, single-blind, positive-controlled tria...OBJECTIVE: To evaluate the effect of ZiYin Xiehuo granules(ZYXH) and Zishen Qinggan granules(ZSQG) on partial precocious puberty(PPP).METHODS: This was a multicenter, randomized, single-blind, positive-controlled trial. A total of 143 pa-tients were assigned to either the ZYXH group or the ZSQG group using a random number table. The ZYXH group received ZYXH three times daily for 6 months and the ZSQG group received ZSQG three times daily for 6 months. Mammary nucleus diameter; the results of uterus, ovarian, and maximum follicle measures; and Chinese medicine symptom pattern scores were compared at baseline and after 3 months and 6 months of treatment.RESULTS: After 3 months' treatment, there were no significant differences between the two groups in mammary nucleus index changes(left 3.4 ± 3.1 vs3.5 ± 3.1, P = 0.790; right 3.0 ± 2.9 vs 3.6 ± 3.0, P =0.719). The uterine volume in the ZYXH group was smaller than that in the ZSQG group(2.1 ± 1.6 vs2.6 ± 2.2, P = 0.006). There were no significant between-group differences in ovarian volume and maximum follicular diameter on either side(ovarian volume: left 1.2 ± 0.7 vs 1.3 ± 0.6, P = 0.8; right1.2 ± 0.7 vs 1.4 ± 1.1, P = 0.984; maximum follicular diameter: left 3.9 ± 1.7 vs 3.5 ± 2.2, P = 0.158; right3.5 ± 1.7 vs 3.9 ± 2.1, P = 0.314).CONCLUSION: ZYXH granules and ZSQG granules both affected the size of the mammary nucleus in girls with PPP, and improved Chinese medicine symptom patterns. ZYXH granules showed slight advantages over ZSQG granules in terms of the decrease in the size of the uterus, ovaries, and ovarian follicles.展开更多
The Bama Xiang pig （BMX） Chinese indigenous breed is a famous early-maturing with a two-end black coat To uncover the genetic basis of the BMX phenotype, we conducted comparative genomic analyses between BMX and Eas...The Bama Xiang pig （BMX） Chinese indigenous breed is a famous early-maturing with a two-end black coat To uncover the genetic basis of the BMX phenotype, we conducted comparative genomic analyses between BMX and East Asian wild boars and Laiwu pigs, respectively. Genes under positive selection were enriched in pathways associated with gonadal hormone and melanin synthesis, consistent with the phenotypic changes observed during development in BMX pigs. We also performed differentially expressed gene analysis based on RNA-seq data from pituitary tissues of BMX and Large White pigs. The CTTNBP2NL, FRS2, KANK4, and KATNAL1 genes were under selection and exhibited expressional changes in the pituitary tissue, which may affect BMX pig puberty. Our study demonstrated the positive selection of early maturity in the development of BMX pigs and advances our knowledge on the role of regulatory elements in puberty evolution in pigs.展开更多
The major royal jelly proteins(MRJPs)are the central constituents responsible for the specific activities of royal jelly.Here MRJPs via oral administration daily for 45 consecutive days were evaluated the effects on t...The major royal jelly proteins(MRJPs)are the central constituents responsible for the specific activities of royal jelly.Here MRJPs via oral administration daily for 45 consecutive days were evaluated the effects on the reproductive parameters in immature female mice(FM).Neonatal FM were divided into four groups fed MRJPs with doses of 0,125,250 and 500 mg/kg/body weight(M125,M250 and M500).The results in M125,M250 and M500 showed that the times of estrus were accelerated by 10.7%,15.5%and 10.7%,the secondary follicles number were increased by 50.7%,78.8%and 38.6%,the Graafian follicles were increased by 600.0%and 774.0%and 150.0%,respectively.M500 induced multi-oocyte follicles.The serum estradiol levels of the three groups were increased by 47.1%,64.9%and 31.1%,the action of MRJPs raising hormone secretion level is mainly via upregulating expression of ERˇgene.Antioxidant parameters of ovarian tissue showed that the malondialdehyde levels in M125 and M250 were decreased,the superoxide dismutase activities and glutathione peroxidase activities in M125 and M250 were increased.In conclusion,MRJPs may accelerate onset of puberty and promote follicular development in FM.Our findings would facilitate better understanding of the benefit effect of MRJPs as the key ingredient in royal jelly on promoting fertility performance.展开更多
Objective To compare the changes in body composition, including fat mass index （FMI） and fat free mass index （FFMI） during puberty development of obese and normal-weight children in China, and to explore the effec...Objective To compare the changes in body composition, including fat mass index （FMI） and fat free mass index （FFMI） during puberty development of obese and normal-weight children in China, and to explore the effect of age and gender on body composition. Methods A total of 356 children at the age of 7-15 years were enrolled in this study. Body composition of 10 normal-weight and obese children in each age group was measured by dual-energy x-ray absorptiometry （DEXA）. FFMI and FMI were calculated according to the following formula： FFMI （kg·m^-2）=FFM（kg）/ height^2（m^2） and FMI（kg·m^-2）=FM （kg）/ height^2（m^2）. Results The fat mass and fat free mass of obese children were significantly higher than those of normal-weight children （P〈0.05）. The FMI and FFMI of obese children increased significantly with age and were higher than those of the same sex, gender, and age normal-weight children （P〈0.05）. Conclusion The levels of fat mass, fat free mass, FMI, and FFMI are different in obese and normal-weight children, and gender effects are significant in boys having higher levels of these indicators than in girls. FFMI and FMI can be used as monitoring indexes in weight control of obese children.展开更多
Objective:To study expressions of netrin-1 and its receptor UNC5 C in female precocious puberty rat hypothalamus,and explore its effect on precocious puberty process.Methods:Forty female one-week-old SD rats were rand...Objective:To study expressions of netrin-1 and its receptor UNC5 C in female precocious puberty rat hypothalamus,and explore its effect on precocious puberty process.Methods:Forty female one-week-old SD rats were randomly divided into four groups:experimental group A(precocious puberty early youth),experimental group B(precocious puberty medium youth),group A(normal pre-puberty).group B(normal early youth) with 10 rats in each group.Precocious puberty experimental rats were induced with Danazol and rals in control group were injected with saline.Uterus and ovaries were removed,specimens were weighed,litems index and ovarian index were calculated,and amount of luteinizing hormone(LH) and follicle-stimulating hormone(FSH) were detected from the blood by ELISA.Real-time PCR was used to delect netrin-1 and its receptor UNC5 C.as well as hypothalamic gonadolropinreleasing hormone(GnRH) mRNA expression in hypothalamus tissues:and then,a coimmunoprecipitation study of interactions between netrin-1 and its receptor UNC5 C was carried out.Results:Relative target gene expression levels of control group A,control group B.experimental group A,and experimental group B(with,3-actin as an internal control for normalization) were as follows:Netrin-1:3.5±0.9,5.4±0.7.4.9±1.0.5.3±0.3:UNC5C:0.8±0.04.1.7±0.2.1.82±0.23.1.58±0.4:GnRH:1.2±0.3.2.7±0.3.2.4±0.7.3.2±0.4.Conclusions:LH and FSH concentrations,netrin-1 and its receptor expression are increased in precocious puberty animal models.展开更多
[ Objective] To observe the disposition and localization of neturopetide Y-Y1 （ NPY-Y1 ） mRNA in hypothalamus, pituitary and ovary during puberty. [ Methed] Three 60-day-old Sujiang sows weighing 20 kg and three 160...[ Objective] To observe the disposition and localization of neturopetide Y-Y1 （ NPY-Y1 ） mRNA in hypothalamus, pituitary and ovary during puberty. [ Methed] Three 60-day-old Sujiang sows weighing 20 kg and three 160-day-old Sujiang sows weighing 80 kg were selected and anaesthetized. The hypothalamus, pituitary and ovary were taken out for preparation of frozen sections. The expression and localization of the NPY-Y1 mRNA in hypothalamus-pituitary-ovary axis was observed by the in situ hybridization. The PBS was substituted for hybridization solution to set up a control. ~ Result] Positive hybridization signals of the NPY-Y1 mRNA were detected in the hypothalamus, pituitary and ovary at different develop- mental stages, and these signals were stronger in the 60-day-old sows （before the puberty） than in the 160-day-old sows （during the puberty）. E Conclusion] The NPY-Y1 mRNA is distributed in the hypothalamus-pituitary-ovary axis and can regulate reproductive process of sows.展开更多
OBJECTIVE:To establish a quantification model of Traditional Chinese Medicine(TCM)syndromes by sampling patients undergoing idiopathic precocious puberty(IPP)and early puberty.METHODS:A questionnaire for classifying a...OBJECTIVE:To establish a quantification model of Traditional Chinese Medicine(TCM)syndromes by sampling patients undergoing idiopathic precocious puberty(IPP)and early puberty.METHODS:A questionnaire for classifying and quantifying TCM syndromes was designed and administered.All the results were analyzed;the relationship between 3 types of syndrome and 47symptoms were summated.Meanwhile,the frequency distribution of each symptom or sign was aggregated.Fuzzy mathematics was used to develop a quantification model ofTCM syndromes.RESULTS:We found that precocious puberty had 3types of syndrome,including hyperactivity of fire due to Yin deficiency(Syndrome I),depressed liver Qi transforming into fire(Syndrome II),and end retention of damp heat(Syndrome III).In the IPP group,Syndrome I was the most common principal syndrome(100%).Forty-six patients(43.81%)werediagnosed with Syndrome I accompanied by Syndrome II and 11(10.48%)were diagnosed with Syndrome I accompanied by Syndrome III.In the early puberty group,Syndrome I was also the main syndrome(98.39%).The degrees of most symptoms were mild to moderate.Reddened tongue was the most common tongue manifestation(62.86%prevalence)in the IPP group.The most common pulse manifestations were slippery pulse,thread pulse,and taut pulse.The Asymptotic Normalization Coefficient(ANC)method was used to quantify the TCM syndromes in 167 cases.Diagnostic accuracy rate reached 91%,comparable to expert diagnosis.CONCLUSION:We find that there are 3 types of syndrome in the IPP group and in the early puberty group.Syndrome I(hyperactivity of fire due to Yin deficiency)is the main syndrome in the two groups.ANC may be an appropriate for quantification model ofTCM syndromes.展开更多
The evidence is scarce on the association between age at puberty and semen quality. A cohort of 320 Danish men aged 18-21 years enrolled in the ＂Healthy Habits for Two＂ birth cohort provided self-reported data on pu...The evidence is scarce on the association between age at puberty and semen quality. A cohort of 320 Danish men aged 18-21 years enrolled in the ＂Healthy Habits for Two＂ birth cohort provided self-reported data on pubertal indicators and delivered semen and blood samples. The results indicated an association between older age at pubertal development and lower semen quality and altered reproductive hormones concentrations as measured in young adult life. Men who had their first nocturnal emission, start of pubic hair growth and first voice break episode when older than 15 years had 37.0%, 45.0% and 32.7% lower sperm concentration; 37.8%, 44.2% and 29.1% lower total sperm count; 7.4%, 13.4% and 15.3% lower testosterone concentration; and 21.3%, 1.5% and 3.7% lower inhibin B concentration, respectively, compared with the men who were younger than 13 years at their first pubertal indicators. Only few of the results were statistically significant, but similar tendencies were seen in several of the reproductive parameters suggesting an association between the timing of pubertal development and reproductive health later in life.展开更多
In order to assess the feasibility of subcutaneous administration of Triptorelin with 6-week intervals for the suppression of pituitary-gonadal axis and changes of clinical signs in girls with idiopathic central preco...In order to assess the feasibility of subcutaneous administration of Triptorelin with 6-week intervals for the suppression of pituitary-gonadal axis and changes of clinical signs in girls with idiopathic central precocious puberty （ICPP）, 46 girls with ICPP were treated with GnRHa. Triptorelin （Decapeptyl, 3.75 mg） was administered subcutaneously （SC） at 6-weeks intervals or intramuscularly （IM） at 4-weeks intervals randomly for more than 12 months consecutively. During GnRHa therapy, clinical parameters and laboratory data, including height, weight, pubertal stage, bone age, uterine volume and ovarian size, serum levels of luteinizing hormone （LH）, follicle stimulating hormone （FSH） and estradiol （E2）, were monitored and analyzed. It was found that both treatment regimes led to regression of precocious puberty and reversal of secondary sexual characteristics. Breast developments regressed. Uterine volume was decreased after treatment, but there was no statistically significant difference. Mean ovarian volume did not change significantly during treatment. The height velocity was decreased significandy from 6.3±1.4 cm/year to 5.8：1：1.2 cm/year in group SC and 6.7±1.3 cm/year to 5.4±1.0 cm/year in group IM, respectively. The rate of bone maturation was reduced significantly during treatment. The ratio of deltaBAgdeltaCA was 1.2±0.2 or 1.3±0.3 at the onset of therapy and decreased significantly after the treatment to 0.7±0.2 or 0.9±0.1, respectively. The predicted adult height was increased significantly and progressively during therapy. The levels of serum LH, FSH and E2 returned to the prepubertal condition. No significant side effects of therapy were noted. The most common side effect during SC treatment was that a non-irritating, 1 cm in di- ameter mass was palpated at the site of subcutaneous injection in the abdominal wall of patients, which disappeared after 6- 12 weeks. Two girls had minimal withdrawal vaginal bleeding episodes after the first injection. It was concluded that both IM and SC triptorelin administrations were clinically effective. They induce profound suppression of hypothalamic-pituitary-gonadal axis while stabilizing height velocity, slowing bone maturation and increasing predicted adult height. These results suggest that subcutaneous injection of triptorelin in 6-weeks intervals at a dosage of 3.75 mg be a safe and acceptable regimen for ICPP.展开更多
BACKGROUND Caused by premature activation of the hypothalamic-pituitary-gonadal axis,there is increasing incidence of central precocious puberty(CPP),especially in girls.Makorin ring finger protein 3(MKRN3),a maternal...BACKGROUND Caused by premature activation of the hypothalamic-pituitary-gonadal axis,there is increasing incidence of central precocious puberty(CPP),especially in girls.Makorin ring finger protein 3(MKRN3),a maternal imprinted gene with a highly conserved sequence,is the most common genetic etiology associated with CPP.Approximately 50 different mutations in MKRN3 have been found in CPP.CASE SUMMARY This case report involves identical twin sisters presenting with premature thelarche at the age of 6 years.The left hand bone age of both patients revealed advanced age(9 years).Pelvic B ultrasound indicated enlargement of the ovaries.Luteinizing hormone(LH)releasing hormone testing confirmed CPP.Wholeexome sequencing detected the c.841C>T mutation in MKRN3,leading to a single base substitution,in the twins.This mutation was inherited from the father and paternal grandmother.After 3 mo of treatment with a gonadotropin-releasing hormone analog,levels of LH,follicle-stimulating hormone,and estradiol in the proband’s sister returned to normal levels.CONCLUSION Here,we report a rare mutation(c.841C>T)in MKRN3 in identical twin sisters with CPP.展开更多
BACKGROUND Recent publications from several countries have reported that more young people(mainly girls)are experiencing precocious puberty(PP)/menarche during the coronavirus disease 2019 pandemic compared to the pas...BACKGROUND Recent publications from several countries have reported that more young people(mainly girls)are experiencing precocious puberty(PP)/menarche during the coronavirus disease 2019 pandemic compared to the past.This variation is attributed to the stress of confinement,lack of exercise,obesity and disturbed sleep patterns.A common feature of the relevant papers,however,is the small number of reported cases of PP.Studies have shown that searches for diseases on the internet also reflect to some extent the epidemiology of these diseases.AIM To estimate,through internet searches for PP,any changes in the epidemiology of PP.METHODS We assessed in Google Trends searches for 21 PP-related terms in English internationally(which practically dwarf searches in other languages),in the years 2017-2021.Additionally,we assessed local searches for selected terms,in English and local languages,in countries where a rise in PP has been reported.Searches were collected in Relative Search Volumes format and analyzed using Kendall’s Tau test,with a statistical significance threshold of P<0.05.RESULTS Internationally,searches for three PP-related terms showed no noticeable change over the study period,while searches for eight terms showed a decrease.An increase was found over time in searches for nine PP-related terms.Of the 17 searches in English and local languages,in countries where a rise in PP has been reported,5 showed a significant increase over time.CONCLUSION Over the study period,more than half of the search terms showed little change or declined.The discrepancy between internet searches for PP and the reported increase in the literature is striking.It would be expected that a true increase in the incidence of PP would also be aptly reflected in Google trends.If our findings are valid,the literature may have been biased.The known secular trend of decreasing age of puberty may also have played a role.展开更多
基金National Natural Science Foundation of China,Grant/Award Number:82101937Guangdong Medical Science and Technology Research Fund Project,China,Grant/Award Number:B2024069Guangzhou Science and Technology Plan Project,China,Grant/Award Number:2024A04J4923 and SL2023A04J02229。
文摘Background:Makorin ring finger protein 3 gene(MKRN3)gene mutation is the most common genetic cause of central precocious puberty(CPP)in children.Due to the lack of ideal MKRN3-modified animal model(MKRN3-modified mice enter puberty only 4–5 days earlier than normal mice),the related research is limited.Methods:Therefore,the MKRN3-modified rabbit was developed using CRISPR(clus-tered regularly interspaced short palindromic repeats)gene editing technology.The genotype identification and phenotype evaluation of MKRN3-modified rabbits were carried out.Results:The first estrus of MKRN3-modified female rabbits was observed~27 days earlier than that of wild-type female rabbits,with a typical CPP phenotype.This study found increased gonadotropin releasing hormone(GnRH)and decreased gonadotropin inhibiting hormone(GnIH)in the hypothalamus of the CPP rabbit model with MKRN3 gene mutation.Although this study failed to fully clarify the pathogenesis of CPP caused by MKRN3 mutation,it found some differentially expressed genes and potential pathways through transcriptome sequencing.Conclusions:This study established a novel CPP model:paternal MKRN3 gene-modified rabbit.It is hoped that the establishment of this model will help researchers better understand,treat,and prevent CPP in the future.
文摘BACKGROUND At present,the clinical mechanisms underlying precocious puberty remain unclear,making effective intervention for children experiencing this condition and rapidly progressive puberty essential.AIM To explore the effects of Zhibai dihuang pills and gonadotropin-releasing hormone analogue(GnRHa)on growth and ovarian function in girls with precocious puberty.METHODS The clinical data of 84 adolescent girls with precocious puberty and rapidly progressive puberty from February 2017 to August 2023 were retrospectively analyzed.Girls were divided into a control group and an observation group,with 42 cases in each group.The control group received diet intervention combined with GnRHa treatment,while the observation group received diet intervention combined with Zhibai dihuang pills+GnRHa treatment.Outcomes such as clinical efficacy,growth indicators,ovarian function,and adverse reactions were compared between the two groups.RESULTS The observation group showed superior clinical efficacy compared to the control group(P<0.05).Prior to the intervention,no significant differences were found in growth or ovarian function between the groups(P>0.05).Post-intervention,the observation group exhibited significantly lower rates in growth,height,and bone age,along with reduced levels of progesterone,testosterone,estradiol,prolactin,luteinizing hormone,and follicle-stimulating hormone compared to the control group(P<0.05).The incidence of adverse reactions was similar across both groups(P>0.05).CONCLUSION Combining Zhibai dihuang pills with GnRHa and dietary intervention effectively improves growth,enhances ovarian function,and minimizes adverse reactions in adolescent girls with precocious and rapidly progressive puberty.
基金Supported by National Natural Science Foundation-funded Project:Study on the Experimental Animal Model of Precocious Puberty with Syndrome of Yin Deficiency and Fire Hyperactivity by Changing the Cycle of Light Exposure(No.81373692)The Constructive Project of Flagship Hospital of Integrated TCM with Western Medicine in Children’s Hospital of Fudan University[No.ZY(2021-2023)-0205-03]the Network Coverage of Coordinated Medical Practice Combined TCM with Western Medicine in Fudan Pediatric Medical Partnerships Union[ZY(2021-2023)-0206-06]。
文摘OBJECTIVE:To elucidate the mechanism of the nourishing Yin and purging fire Chinese herbal mixture(NYPF)in delaying light-induced premature puberty in rats.METHODS:Twenty-one days old female SpragueDawley rats were randomly assigned to normal group(N),long light exposure group(L),NYPF and normal saline group(NS).Rats in the L,NYPF and NS groups were exposed to 16 h:350 lux light/8 h:dark,while rats in the N group were exposed to 12 h:50 lux light/12 h:dark.NYPF and normal saline was administered to the rats in the NYPF group or NS group,respectively,from day 21.Five rats in every group were sacrificed at 9 p.m.on day 28(P28),on the day when rat's vulva opened in the L group(L-VO),on the day when the first estrous interphase occurred in rats of L group(L-E1),and on the day when the second estrous interphase occurred in rats of L group(L-E2),respectively.RESULITS:On day 34,all rats in the L group,80%of rats in the NS group,40%of rats in the N group,and 20%of rats in the NYPF group showed complete opening of the vulva.At P28,m RNA level of hypothalamic kisspeptin(Kiss-1)in the L group was significantly higher than that in the N group(P<0.05).The rats in the L and NS groups had significantly lower hypothalamic argininephenylalanine-amide(RFamide)-related peptide 3(RFRP-3)m RNA levels than those in the N group(P<0.05),whereas RFRP-3 m RNA level was significantly higher in the NYPF group than that in the L group(P<0.05).At L-VO,the ovarian index of the L and NS groups was significantly higher than that of the N group(P<0.05)and estradiol(E2)level of the NYPF group was significantly lower than that of the N and NS groups(P<0.05);hypothalamic Kiss-1 m RNA level in the L and NS groups was significantly higher than that in the N and NYPF groups(P<0.05),whereas hypothalamic RFRP-3 m RNA level in the L,NYPF,and NS groups was significantly lower than that in the N group(P<0.05).At L-E1,E2 level of the L and NS groups was significantly higher than that of the N group(P<0.01),whereas it was significantly lower in the NYPF group than that of the N,L,and NS groups(P<0.01),and serum luteinizing hormone level of the L and NS groups was significantly higher than that of the N group(P<0.05);levels of serum melatonin and ovarian melatonin receptor 1(MT-1)m RNA in the L,NYPF,and NS groups were significantly lower than those in the N group(P<0.05).At L-E2,the uterine organ index of the NYPF group was significantly lower than that of the L group(P<0.05);and ovarian MT-1 m RNA level of the L and NS groups was significantly lower than that in the N group(P<0.05).CONCLUSIONS:NYPF can delay puberty onset in rats exposed to strong light for a prolonged duration,and regulation of the gene expression of Kiss-1 and RFRP-3 in the hypothalamus has been suggested as one of the mechanisms.
文摘Central precocious puberty secondary to Leydig cell tumors is rare in children. We retrospectively analyzed the mid- to long-term follow-up data of patients with Leydig cell tumors. The clinical data of 12 consecutive patients who were treated at Beijing Children’s Hospital, Capital Medical University (Beijing, China), between January 2016 and October 2023 were retrospectively reviewed. Clinical evaluations, including physical examination, hormone examination, serum tumor marker analysis, abdominal and scrotal ultrasound, chest X-ray, and bone age measurement, were conducted before surgery and at follow-up time points. Surgical approaches were selected according to the individual conditions. Patients with an abnormal hormonal status and suspected of having central precocious puberty were referred to endocrinologists to confirm the diagnosis. Subsequently, gonadotropin-releasing hormone analog therapy was proposed. The mean patient age was 81.3 (range: 40–140) months at the time of the operation. Ten patients had peripheral precocious puberty at admission. All patients had elevated preoperative testosterone levels, whereas tumor marker levels were normal. Testis-sparing surgery was performed in eleven patients, and radical orchiectomy was performed in one patient. The follow-up duration (mean ± standard deviation) was 36.2 ± 25.3 months. Five patients had central precocious puberty, with a mean duration of 3.4 (range: 1–6) months postoperatively. Three patients were receiving gonadotropin-releasing hormone analog therapy, and good suppression of puberty was observed. No risk factors were found for secondary central precocious puberty. There was a high prevalence of central precocious puberty secondary to Leydig cell tumors in our study. Gonadotropin-releasing hormone analog therapy has satisfactory treatment effects. Larger sample sizes and long-term follow-up are needed in future studies.
基金funded by New Zealand dairy farmers through Dairy NZ Inc. and by the New Zealand Ministry of Business,Innovation and Employment (DRCX1302)support was kindly received from LIC and CRV
文摘Background Many phenotypes in animal breeding are derived from incomplete measures,especially if they are challenging or expensive to measure precisely.Examples include time-dependent traits such as reproductive status,or lifespan.Incomplete measures for these traits result in phenotypes that are subject to left-,interval-and rightcensoring,where phenotypes are only known to fall below an upper bound,between a lower and upper bound,or above a lower bound respectively.Here we compare three methods for deriving phenotypes from incomplete data using age at first elevation(>1 ng/mL)in blood plasma progesterone(AGEP4),which generally coincides with onset of puberty,as an example trait.Methods We produced AGEP4 phenotypes from three blood samples collected at about 30-day intervals from approximately 5,000 Holstein–Friesian or Holstein–Friesian×Jersey cross-bred dairy heifers managed in 54 seasonal-calving,pasture-based herds in New Zealand.We used these actual data to simulate 7 different visit scenarios,increasing the extent of censoring by disregarding data from one or two of the three visits.Three methods for deriving phenotypes from these data were explored:1)ordinal categorical variables which were analysed using categorical threshold analysis;2)continuous variables,with a penalty of 31 d assigned to right-censored phenotypes;and 3)continuous variables,sampled from within a lower and upper bound using a data augmentation approach.Results Credibility intervals for heritability estimations overlapped across all methods and visit scenarios,but estimated heritabilities tended to be higher when left censoring was reduced.For sires with at least 5 daughters,the correlations between estimated breeding values(EBVs)from our three-visit scenario and each reduced data scenario varied by method,ranging from 0.65 to 0.95.The estimated breed effects also varied by method,but breed differences were smaller as phenotype censoring increased.Conclusion Our results indicate that using some methods,phenotypes derived from one observation per offspring for a time-dependent trait such as AGEP4 may provide comparable sire rankings to three observations per offspring.This has implications for the design of large-scale phenotyping initiatives where animal breeders aim to estimate variance parameters and estimated breeding values(EBVs)for phenotypes that are challenging to measure or prohibitively expensive.
文摘Background: Hypothalamic hamartoma is a rare non-neoplastic lesion, typically identified in early childhood during investigations for precocious puberty and/or gelastic seizures. However, cases of diagnosis even earlier or during fetal development have been documented. Case Presentation: A newborn girl was diagnosed with hydrocephalus during pregnancy. An MRI revealed a large oval hypothalamic process, which suggested a hypothalamic hamartoma. At the age of 2, she experienced alternating crying and laughing seizures, followed by a decrease in visual acuity. Due to involvement of the optic pathways, surgery was not performed and she underwent antiepileptic medicines and gamma knife radiotherapy. At the age of 5 years and 3 months, she presented with breast development and laboratory tests confirmed central precocious puberty. Quarterly injections of GnRH agonists have since been administered with favorable results. Conclusion: Early-diagnosed hypothalamic hamartomas require close monitoring, by an experienced multidisciplinary, to promptly detect and treat potential complications, especially precocious puberty, and prevent any undesirable impact on final height.
文摘Objective:This study aimed to evaluate the therapeutic effects of leuprolide acetate extended-release microspheres for injection in children with pediatric precocious puberty.Methods:A total of 110 cases of pediatric precocious puberty admitted between January 2019 and December 2021 were selected and randomized into two groups using a random number table,with 55 cases in the control group and 55 cases in the experimental group.The control group received conventional treatment,while the experimental group was treated with leuprolide acetate extended-release microspheres for injection.The therapeutic effects were observed,and changes in sex hormone levels,ovarian volume,growth indices,and the incidence of adverse reactions were statistically compared between the groups.Results:The experimental group demonstrated superior outcomes in terms of sex hormone levels,ovarian volume,and growth indices compared to the control group.Additionally,the incidence of adverse reactions in the experimental group was significantly lower(P<0.05).Conclusion:The application of leuprolide acetate extended-release microspheres for the treatment of pediatric precocious puberty is associated with improved therapeutic effects and higher safety.
文摘Puberty is a pivotal biological process that completes sexual maturation to achieve full reproductive capability.It is a major transformational period of life,whose timing is strongly affected by genetic makeup of the individual,along with various internal and external factors.Although the exact mechanism for initiation of the cascade of molecular events that culminate in puberty is not yet known,the process of pubertal onset involves interaction of numerous complex signaling pathways of hypothalamopituitary-testicular(HPT)axis.We developed a classification of the mechanisms involved in male puberty that allowed placing many genes into physiological context.These include(i)hypothalamic development during embryogenesis,(ii)synaptogenesis where gonadotropin releasing hormone(GnRH)neurons form neuronal connections with suprahypothalamic neurons,(iii)maintenance of neuron homeostasis,(iv)regulation of synthesis and secretion of GnRH,(v)appropriate receptors/proteins on neurons governing GnRH production and release,(vi)signaling molecules activated by the receptors,(vii)the synthesis and release of GnRH,(viii)the production and release of gonadotropins,(ix)testicular development,(x)synthesis and release of steroid hormones from testes,and(xi)the action of steroid hormones in downstream effector tissues.Defects in components of this system during embryonic development,childhood/adolescence,or adulthood may disrupt/nullify puberty,leading to long-term male infertility and/or hypogonadism.This review provides a list of 598 genes involved in the development of HPT axis and classified according to this schema.Furthermore,this review identifies a subset of 75 genes for which genetic mutations are reported to delay or disrupt male puberty.
文摘In boys, central precocious puberty （CPP） is the appearance of secondary sex characteristics driven by pituitary gonadotropin secretion before the age of 9 years. In the last years, relevant improvements in the treatment of CPP have been achieved. Because CPP is rare in boys, the majority of papers on this issue focus on girls and do not address specific features of male patients regarding end results and safety. In the present paper, recent advances of CPP management with GnRH analogs in men are summarized. End results in untreated and treated patients are also reviewed by an analysis of the recently published literature on treatment of CPP in men. The available data indicate that therapy with GnRH analogs can improve final height into the range of target height without significant adverse short-term and long-term effects, but longer follow-up of larger series of patients is still required to draw definitive conclusions.
基金Supported by the Shanghai Integrated Chinese and Western Medicine Key Diseases Construction Projects(No.zxbz2012-14)a Medical Guidance Item of the Shanghai Science and Technology Commission(No.12401906900)+1 种基金by the Chinese Medicine Prescription Project of the Shanghai Shenkang Hospital Development Center(No.SHDC12012414)by the Development Project of the Shanghai Peak
文摘OBJECTIVE: To evaluate the effect of ZiYin Xiehuo granules(ZYXH) and Zishen Qinggan granules(ZSQG) on partial precocious puberty(PPP).METHODS: This was a multicenter, randomized, single-blind, positive-controlled trial. A total of 143 pa-tients were assigned to either the ZYXH group or the ZSQG group using a random number table. The ZYXH group received ZYXH three times daily for 6 months and the ZSQG group received ZSQG three times daily for 6 months. Mammary nucleus diameter; the results of uterus, ovarian, and maximum follicle measures; and Chinese medicine symptom pattern scores were compared at baseline and after 3 months and 6 months of treatment.RESULTS: After 3 months' treatment, there were no significant differences between the two groups in mammary nucleus index changes(left 3.4 ± 3.1 vs3.5 ± 3.1, P = 0.790; right 3.0 ± 2.9 vs 3.6 ± 3.0, P =0.719). The uterine volume in the ZYXH group was smaller than that in the ZSQG group(2.1 ± 1.6 vs2.6 ± 2.2, P = 0.006). There were no significant between-group differences in ovarian volume and maximum follicular diameter on either side(ovarian volume: left 1.2 ± 0.7 vs 1.3 ± 0.6, P = 0.8; right1.2 ± 0.7 vs 1.4 ± 1.1, P = 0.984; maximum follicular diameter: left 3.9 ± 1.7 vs 3.5 ± 2.2, P = 0.158; right3.5 ± 1.7 vs 3.9 ± 2.1, P = 0.314).CONCLUSION: ZYXH granules and ZSQG granules both affected the size of the mammary nucleus in girls with PPP, and improved Chinese medicine symptom patterns. ZYXH granules showed slight advantages over ZSQG granules in terms of the decrease in the size of the uterus, ovaries, and ovarian follicles.
基金supported by grants from the National Natural Science Foundation of China(31472000)National 973 Program of China(2013CB835203)Animal Branch of the Germplasm Bank of Wild Species,Chinese Academy of Sciences(Large Research Infrastructure Funding)
文摘The Bama Xiang pig （BMX） Chinese indigenous breed is a famous early-maturing with a two-end black coat To uncover the genetic basis of the BMX phenotype, we conducted comparative genomic analyses between BMX and East Asian wild boars and Laiwu pigs, respectively. Genes under positive selection were enriched in pathways associated with gonadal hormone and melanin synthesis, consistent with the phenotypic changes observed during development in BMX pigs. We also performed differentially expressed gene analysis based on RNA-seq data from pituitary tissues of BMX and Large White pigs. The CTTNBP2NL, FRS2, KANK4, and KATNAL1 genes were under selection and exhibited expressional changes in the pituitary tissue, which may affect BMX pig puberty. Our study demonstrated the positive selection of early maturity in the development of BMX pigs and advances our knowledge on the role of regulatory elements in puberty evolution in pigs.
基金The authors are grateful to Dr.Quanwei Wei from Nanjing Agricultural University,Nanjing,China for his technical assistance.This work was supported by the National Natural Science Foundation of China(no.31271848)。
文摘The major royal jelly proteins(MRJPs)are the central constituents responsible for the specific activities of royal jelly.Here MRJPs via oral administration daily for 45 consecutive days were evaluated the effects on the reproductive parameters in immature female mice(FM).Neonatal FM were divided into four groups fed MRJPs with doses of 0,125,250 and 500 mg/kg/body weight(M125,M250 and M500).The results in M125,M250 and M500 showed that the times of estrus were accelerated by 10.7%,15.5%and 10.7%,the secondary follicles number were increased by 50.7%,78.8%and 38.6%,the Graafian follicles were increased by 600.0%and 774.0%and 150.0%,respectively.M500 induced multi-oocyte follicles.The serum estradiol levels of the three groups were increased by 47.1%,64.9%and 31.1%,the action of MRJPs raising hormone secretion level is mainly via upregulating expression of ERˇgene.Antioxidant parameters of ovarian tissue showed that the malondialdehyde levels in M125 and M250 were decreased,the superoxide dismutase activities and glutathione peroxidase activities in M125 and M250 were increased.In conclusion,MRJPs may accelerate onset of puberty and promote follicular development in FM.Our findings would facilitate better understanding of the benefit effect of MRJPs as the key ingredient in royal jelly on promoting fertility performance.
基金supported by the 973 Project "Mechanism of Type 2 Diabetes Progression" (No. 2006CB503900) from Ministry of Science and Technology of ChinaScientific Program from General Administration of Sport of China (No. 06134)
文摘Objective To compare the changes in body composition, including fat mass index （FMI） and fat free mass index （FFMI） during puberty development of obese and normal-weight children in China, and to explore the effect of age and gender on body composition. Methods A total of 356 children at the age of 7-15 years were enrolled in this study. Body composition of 10 normal-weight and obese children in each age group was measured by dual-energy x-ray absorptiometry （DEXA）. FFMI and FMI were calculated according to the following formula： FFMI （kg·m^-2）=FFM（kg）/ height^2（m^2） and FMI（kg·m^-2）=FM （kg）/ height^2（m^2）. Results The fat mass and fat free mass of obese children were significantly higher than those of normal-weight children （P〈0.05）. The FMI and FFMI of obese children increased significantly with age and were higher than those of the same sex, gender, and age normal-weight children （P〈0.05）. Conclusion The levels of fat mass, fat free mass, FMI, and FFMI are different in obese and normal-weight children, and gender effects are significant in boys having higher levels of these indicators than in girls. FFMI and FMI can be used as monitoring indexes in weight control of obese children.
基金Project supported by the natural science foundation of Hebei province(No.H2013209314)
文摘Objective:To study expressions of netrin-1 and its receptor UNC5 C in female precocious puberty rat hypothalamus,and explore its effect on precocious puberty process.Methods:Forty female one-week-old SD rats were randomly divided into four groups:experimental group A(precocious puberty early youth),experimental group B(precocious puberty medium youth),group A(normal pre-puberty).group B(normal early youth) with 10 rats in each group.Precocious puberty experimental rats were induced with Danazol and rals in control group were injected with saline.Uterus and ovaries were removed,specimens were weighed,litems index and ovarian index were calculated,and amount of luteinizing hormone(LH) and follicle-stimulating hormone(FSH) were detected from the blood by ELISA.Real-time PCR was used to delect netrin-1 and its receptor UNC5 C.as well as hypothalamic gonadolropinreleasing hormone(GnRH) mRNA expression in hypothalamus tissues:and then,a coimmunoprecipitation study of interactions between netrin-1 and its receptor UNC5 C was carried out.Results:Relative target gene expression levels of control group A,control group B.experimental group A,and experimental group B(with,3-actin as an internal control for normalization) were as follows:Netrin-1:3.5±0.9,5.4±0.7.4.9±1.0.5.3±0.3:UNC5C:0.8±0.04.1.7±0.2.1.82±0.23.1.58±0.4:GnRH:1.2±0.3.2.7±0.3.2.4±0.7.3.2±0.4.Conclusions:LH and FSH concentrations,netrin-1 and its receptor expression are increased in precocious puberty animal models.
文摘[ Objective] To observe the disposition and localization of neturopetide Y-Y1 （ NPY-Y1 ） mRNA in hypothalamus, pituitary and ovary during puberty. [ Methed] Three 60-day-old Sujiang sows weighing 20 kg and three 160-day-old Sujiang sows weighing 80 kg were selected and anaesthetized. The hypothalamus, pituitary and ovary were taken out for preparation of frozen sections. The expression and localization of the NPY-Y1 mRNA in hypothalamus-pituitary-ovary axis was observed by the in situ hybridization. The PBS was substituted for hybridization solution to set up a control. ~ Result] Positive hybridization signals of the NPY-Y1 mRNA were detected in the hypothalamus, pituitary and ovary at different develop- mental stages, and these signals were stronger in the 60-day-old sows （before the puberty） than in the 160-day-old sows （during the puberty）. E Conclusion] The NPY-Y1 mRNA is distributed in the hypothalamus-pituitary-ovary axis and can regulate reproductive process of sows.
基金Supported by the National Natural Science Foundation of China(No.81072841)the Shanghai Science and Technology Research Grant Program(No.09dZ1971600)State Key Clinical Department of TCM pediatrics
文摘OBJECTIVE:To establish a quantification model of Traditional Chinese Medicine(TCM)syndromes by sampling patients undergoing idiopathic precocious puberty(IPP)and early puberty.METHODS:A questionnaire for classifying and quantifying TCM syndromes was designed and administered.All the results were analyzed;the relationship between 3 types of syndrome and 47symptoms were summated.Meanwhile,the frequency distribution of each symptom or sign was aggregated.Fuzzy mathematics was used to develop a quantification model ofTCM syndromes.RESULTS:We found that precocious puberty had 3types of syndrome,including hyperactivity of fire due to Yin deficiency(Syndrome I),depressed liver Qi transforming into fire(Syndrome II),and end retention of damp heat(Syndrome III).In the IPP group,Syndrome I was the most common principal syndrome(100%).Forty-six patients(43.81%)werediagnosed with Syndrome I accompanied by Syndrome II and 11(10.48%)were diagnosed with Syndrome I accompanied by Syndrome III.In the early puberty group,Syndrome I was also the main syndrome(98.39%).The degrees of most symptoms were mild to moderate.Reddened tongue was the most common tongue manifestation(62.86%prevalence)in the IPP group.The most common pulse manifestations were slippery pulse,thread pulse,and taut pulse.The Asymptotic Normalization Coefficient(ANC)method was used to quantify the TCM syndromes in 167 cases.Diagnostic accuracy rate reached 91%,comparable to expert diagnosis.CONCLUSION:We find that there are 3 types of syndrome in the IPP group and in the early puberty group.Syndrome I(hyperactivity of fire due to Yin deficiency)is the main syndrome in the two groups.ANC may be an appropriate for quantification model ofTCM syndromes.
文摘The evidence is scarce on the association between age at puberty and semen quality. A cohort of 320 Danish men aged 18-21 years enrolled in the ＂Healthy Habits for Two＂ birth cohort provided self-reported data on pubertal indicators and delivered semen and blood samples. The results indicated an association between older age at pubertal development and lower semen quality and altered reproductive hormones concentrations as measured in young adult life. Men who had their first nocturnal emission, start of pubic hair growth and first voice break episode when older than 15 years had 37.0%, 45.0% and 32.7% lower sperm concentration; 37.8%, 44.2% and 29.1% lower total sperm count; 7.4%, 13.4% and 15.3% lower testosterone concentration; and 21.3%, 1.5% and 3.7% lower inhibin B concentration, respectively, compared with the men who were younger than 13 years at their first pubertal indicators. Only few of the results were statistically significant, but similar tendencies were seen in several of the reproductive parameters suggesting an association between the timing of pubertal development and reproductive health later in life.
文摘In order to assess the feasibility of subcutaneous administration of Triptorelin with 6-week intervals for the suppression of pituitary-gonadal axis and changes of clinical signs in girls with idiopathic central precocious puberty （ICPP）, 46 girls with ICPP were treated with GnRHa. Triptorelin （Decapeptyl, 3.75 mg） was administered subcutaneously （SC） at 6-weeks intervals or intramuscularly （IM） at 4-weeks intervals randomly for more than 12 months consecutively. During GnRHa therapy, clinical parameters and laboratory data, including height, weight, pubertal stage, bone age, uterine volume and ovarian size, serum levels of luteinizing hormone （LH）, follicle stimulating hormone （FSH） and estradiol （E2）, were monitored and analyzed. It was found that both treatment regimes led to regression of precocious puberty and reversal of secondary sexual characteristics. Breast developments regressed. Uterine volume was decreased after treatment, but there was no statistically significant difference. Mean ovarian volume did not change significantly during treatment. The height velocity was decreased significandy from 6.3±1.4 cm/year to 5.8：1：1.2 cm/year in group SC and 6.7±1.3 cm/year to 5.4±1.0 cm/year in group IM, respectively. The rate of bone maturation was reduced significantly during treatment. The ratio of deltaBAgdeltaCA was 1.2±0.2 or 1.3±0.3 at the onset of therapy and decreased significantly after the treatment to 0.7±0.2 or 0.9±0.1, respectively. The predicted adult height was increased significantly and progressively during therapy. The levels of serum LH, FSH and E2 returned to the prepubertal condition. No significant side effects of therapy were noted. The most common side effect during SC treatment was that a non-irritating, 1 cm in di- ameter mass was palpated at the site of subcutaneous injection in the abdominal wall of patients, which disappeared after 6- 12 weeks. Two girls had minimal withdrawal vaginal bleeding episodes after the first injection. It was concluded that both IM and SC triptorelin administrations were clinically effective. They induce profound suppression of hypothalamic-pituitary-gonadal axis while stabilizing height velocity, slowing bone maturation and increasing predicted adult height. These results suggest that subcutaneous injection of triptorelin in 6-weeks intervals at a dosage of 3.75 mg be a safe and acceptable regimen for ICPP.
基金by the key Research and Development Program of Zhejiang Province(No.2020C03121).
文摘BACKGROUND Caused by premature activation of the hypothalamic-pituitary-gonadal axis,there is increasing incidence of central precocious puberty(CPP),especially in girls.Makorin ring finger protein 3(MKRN3),a maternal imprinted gene with a highly conserved sequence,is the most common genetic etiology associated with CPP.Approximately 50 different mutations in MKRN3 have been found in CPP.CASE SUMMARY This case report involves identical twin sisters presenting with premature thelarche at the age of 6 years.The left hand bone age of both patients revealed advanced age(9 years).Pelvic B ultrasound indicated enlargement of the ovaries.Luteinizing hormone(LH)releasing hormone testing confirmed CPP.Wholeexome sequencing detected the c.841C>T mutation in MKRN3,leading to a single base substitution,in the twins.This mutation was inherited from the father and paternal grandmother.After 3 mo of treatment with a gonadotropin-releasing hormone analog,levels of LH,follicle-stimulating hormone,and estradiol in the proband’s sister returned to normal levels.CONCLUSION Here,we report a rare mutation(c.841C>T)in MKRN3 in identical twin sisters with CPP.
基金Athanasios Tselebis,ORCID number: 0000-0002-2591-965XLina Zabuliene ,ORCID number:0000-0002-7889-0862+1 种基金Charalampos Milionis ,ORCID number:0000-0003-2442-3772Corresponding author:Ioannis Ilias,MD,PhD,Consultant Physician-Scientist,Department of Endocrinology,Elena Venizelou General and Maternity Hospital,2,Elena Venizelou Square,Athens GR-11521,Greece.iiliasmd@yahoo.com,ORCID number: 0000-0001-5718-7441.
文摘BACKGROUND Recent publications from several countries have reported that more young people(mainly girls)are experiencing precocious puberty(PP)/menarche during the coronavirus disease 2019 pandemic compared to the past.This variation is attributed to the stress of confinement,lack of exercise,obesity and disturbed sleep patterns.A common feature of the relevant papers,however,is the small number of reported cases of PP.Studies have shown that searches for diseases on the internet also reflect to some extent the epidemiology of these diseases.AIM To estimate,through internet searches for PP,any changes in the epidemiology of PP.METHODS We assessed in Google Trends searches for 21 PP-related terms in English internationally(which practically dwarf searches in other languages),in the years 2017-2021.Additionally,we assessed local searches for selected terms,in English and local languages,in countries where a rise in PP has been reported.Searches were collected in Relative Search Volumes format and analyzed using Kendall’s Tau test,with a statistical significance threshold of P<0.05.RESULTS Internationally,searches for three PP-related terms showed no noticeable change over the study period,while searches for eight terms showed a decrease.An increase was found over time in searches for nine PP-related terms.Of the 17 searches in English and local languages,in countries where a rise in PP has been reported,5 showed a significant increase over time.CONCLUSION Over the study period,more than half of the search terms showed little change or declined.The discrepancy between internet searches for PP and the reported increase in the literature is striking.It would be expected that a true increase in the incidence of PP would also be aptly reflected in Google trends.If our findings are valid,the literature may have been biased.The known secular trend of decreasing age of puberty may also have played a role.
