Objective: Prokineticin-1 (PROK1) is a recently described protein with a wide range of functions including tissue specific angiogenesis, modulation of inflammatory responses and regulation of haematopoiesis. PROK1 has...Objective: Prokineticin-1 (PROK1) is a recently described protein with a wide range of functions including tissue specific angiogenesis, modulation of inflammatory responses and regulation of haematopoiesis. PROK1 has been found in the steroidogenic organs like ovary, testis, adrenal and specially placenta and they have been found to have a role in development of the olfactory system and GnRH system. The aim was to update the role of PROK1 and PROK2 inhuman reproduction since the review was provided by Maldono-Perez (2007) on the potentials of prokineticins in reproduction. Design: A review of international scientific literature by a search of Pubmed and the authors files was done for citation of articles relevant to prokineticins in reproduction, be it its role in ovary, testis, uterus with special emphasis on implantation, normal pregnancy, in labour, pathophysiological states like tubal pregnancy, pcos, various genital tumours, and cases of isolated hypogonadotropic hypogonadism with mutations with PROK2/ PROKR2 and studies detailing functional mechanisms. Results: In the normal cycle, PROK1 has been found to have important roles in implantation, regulating several genes like COX-2, IL-8, IL-11, CTGF related to implantation. Initially murine studies revealed a critical role of PROK2 pathway on olfactory bulb morphogenesis and GnRH secretion which was accidentally discovered and since then several studies on mutations in PROK2/PROKR2 showed that they underlie some case of KS in humans. Although in mouse heterozygote state is not associated with clinical phenotype, most of human mutations are heterozygous. Conclusions: Role of PROK-1 in the process of implantation, with a deeper understanding of the process success rates in IVF and ART can be improved, besides understanding the pathophysiology of tubal pregnancy. Further presence in ovarian follicles of PROK1 can be used to plan a strategy for treating pcos. Development of antagonism of PROK’S may be a helpful strategy in treating preterm labour.展开更多
Background: In Vitro Fertilization/Intracytoplasmic Sperm Injection (IVF/ICSI) represents the final step in the management of Polycystic Ovarian Syndrome (PCOS). Our objective was to study the association between PCOS...Background: In Vitro Fertilization/Intracytoplasmic Sperm Injection (IVF/ICSI) represents the final step in the management of Polycystic Ovarian Syndrome (PCOS). Our objective was to study the association between PCOS phenotypes and IVF/ICSI results in women admitted to Gynaecological Endoscopic Surgery and Human Reproductive Teaching Hospital (CHRACERH). Material and Method: We carried out a cohort study with historical-prospective data collection over a period of seven years (January 2016 to March 2023) at Chracerh. PCOS patients were subdivided into 4 subgroups A, B, C and D. Results: We recruited 128 patients including 64 PCOS patients divided into four phenotypes and 64 non-PCOS patients constituting the control group. Phenotype D without hyperandrogenism had used the lowest dose of gonadotropins, i.e. 1939.7 ± 454.3 IU, and had produced a greater quantity of estradiol on the day ovulation was triggered (6529.8 ± 4324.8 ng/ml). The average number of punctured follicles and mature oocytes were higher in the phenotype D group. Ovarian hyperstimulation syndrome (OHSS) occurred mainly in phenotype D (3/35), with an estimated prevalence of 2.3%. The fertilization rate seemed lower in the hyperandrogenic phenotypes A, B, C compared to the group without hyperandrogenism without significant difference (p = 0.461). The biological pregnancy rate and live birth rate were comparable between the different groups. Conclusion: Phenotype D used less dose of gonadotropins. Biological pregnancy and live birth rates were comparable between the different phenotypes.展开更多
Background: Since 2021, high-risk Human Papilloma Virus (HR-HPV) testing has been the recommended screening test for cervical cancer for all settings;either used alone in a “test and treat” strategy, or with a triag...Background: Since 2021, high-risk Human Papilloma Virus (HR-HPV) testing has been the recommended screening test for cervical cancer for all settings;either used alone in a “test and treat” strategy, or with a triage test, with or without biopsy, before treatment. Cameroon has rolled out immunization against HPV 16 and 18, but studies show a higher prevalence of non-16/18 HR-HPV types. Objectives: Determine the prevalence of precancerous lesions, in women with HR-HPV infection and evaluate association of digital cervicography (DC) VIA/VILI positivity with HPV serotype, as a measure of their contribution to precancer and cancer incidence. Methodology: The study was cross-sectional, descriptive, and analytic. It took place at the Etoug-Ebe and Ekoudoum Baptist Hospitals in Yaoundé, during the period April-September 2022. We reviewed the records of women screened for cervical cancer between February 2020 and December 2021 and evaluated the prevalence of lesions on digital cervicography (DC) with VIA/VILI for women positive for HR-HPV serotypes. The data were analyzed using SPSS version 20.0 for Windows. P values Results: We identified 315 cases with a positive HR-HPV deoxyribonucleic acid (DNA) test, 224 (71.1%) had a DC VIA/VILI triage test done. Of these, 30 (13.4%) women had a positive DC VIA/VILI, with five women (2.2%) having lesions suggestive of cancer. Out of 11 cases positive for HPV 16 alone, 05 (45.5%) had a positive DC VIA/VILI test. Of the 14 cases positive for HPV 18 alone, 03 (21.4%) had a positive VIA/VILI, meanwhile only 19 (10.7%) of the 177 cases positive for non-16/18 HPV had a positive VIA/VILI test. Conclusion: A high proportion of women (13.4%) with HR HPV had a positive DC VIA/VILI, with a significant proportion (2.2%) having lesions suggestive of invasive cervical cancer HR-HPV serotype was associated with DC VIA/VILI positivity;HPV 16 had the strongest association (45.5%), followed by HPV 18 (21.4%), and non-16/18 HR-HPV (10.7%), suggesting a decreasing order of oncogenicity.展开更多
Infertility has become one of the most serious diseases worldwide,and 50% of this disease can be attributed to male-related factors.Spermatogenesis,by definition,is a complex process by which spermatogonial stem cells...Infertility has become one of the most serious diseases worldwide,and 50% of this disease can be attributed to male-related factors.Spermatogenesis,by definition,is a complex process by which spermatogonial stem cells(SSCs)self-renew to maintain stem cell population within the testes and differentiate into mature spermatids.It is of great significance to uncover gene regulation and signaling pathways that are involved in the fate determinations of SSCs with aims to better understand molecular mechanisms underlying human spermatogenesis and identify novel targets for gene therapy of male infertility.Significant achievement has recently been made in demonstrating the signaling molecules and pathways mediating the fate decisions of mammalian SSCs.In this review,we address key gene regulation and crucial signaling transduction pathways in controlling the self-renewal,differentiation,and apoptosis of SSCs,and we illustrate the networks of genes and signaling pathways in SSC fate determinations.We also highlight perspectives and future directions in SSC regulation by genes and their signaling pathways.This review could provide novel insights into the genetic regulation of normal and abnormal spermatogenesis and offer molecular targets to develop new approaches for gene therapy of male infertility.展开更多
Azoospermia, defined as a complete absence of spermatozoa in the ejaculate, is a relatively common condition among infertile men. Establishing the etiological diagnosis can be challenging and often requires various in...Azoospermia, defined as a complete absence of spermatozoa in the ejaculate, is a relatively common condition among infertile men. Establishing the etiological diagnosis can be challenging and often requires various investigations. This cross-sectional study, conducted in Cotonou among 35 azoospermic men, aimed to assess the role of biochemical analysis of seminal fluid in determining the etiological diagnosis. The results revealed significant heterogeneity in biochemical profiles. Most of the patients had normal levels of alpha-glucosidase, fructose, and zinc, indicating normal accessory gland function and suggesting non-obstructive azoospermia. However, a significant subgroup exhibited abnormalities in these markers, suggesting a possible obstructive azoospermia. The heterogeneity in biochemical profiles observed in this study highlights the need for further studies to better characterize azoospermia in Benin.展开更多
Hereditary spastic paraplegias(HSPs)refer to a genetically and clinically heterogeneous group of neurodegenerative disorders characterized by the degeneration of motor neurons.To date,a significant number of patients ...Hereditary spastic paraplegias(HSPs)refer to a genetically and clinically heterogeneous group of neurodegenerative disorders characterized by the degeneration of motor neurons.To date,a significant number of patients still have not received a definite genetic diagnosis.Therefore,identifying unreported causative genes continues to be of great importance.Here,we perform whole-exome sequencing in a cohort of Chinese HSP patients.Three homozygous variants(p.L604W,p.S517F,and p.T984A)within the sterol regulatory element-binding factor 2(SREBF2)gene are identified in one autosomal recessive family and two sporadic patients,respectively.Co-segregation is confirmed by Sanger sequencing in all available members.The three variants are rare in the public or in-house database and are predicted to be damaging.The biological impacts of variants in SREBF2 are examined by functional experiments in patient-derived fibroblasts and Drosophila.We find that the variants upregulate cellular cholesterol due to the overactivation of SREBP2,eventually impairing the autophagosomal and lysosomal functions.The overexpression of the mature form of SREBP2 leads to locomotion defects in Drosophila.Our findings identify SREBF2 as a causative gene for HSP and highlight the impairment of cholesterol as a critical pathway for HSP.展开更多
Dear Editor,We are much obliged that Hadziselimovic1 has used our data2 to highlight the substantial proportion of boys with cryptorchidism where gonadotropin insufficiency is an important factor related to the pathog...Dear Editor,We are much obliged that Hadziselimovic1 has used our data2 to highlight the substantial proportion of boys with cryptorchidism where gonadotropin insufficiency is an important factor related to the pathogenesis.We have recently presented a study on a series of 453 consecutive boys with bilateral nonsyndromic cryptorchidism,in which we conducted hormonal evaluations and assessed germ cell numbers in testicular biopsies.3 In this series,45%of the boys were classified as having gonadotropin insufficiency.3 Identifying these patients at the time of surgery is important.A recent follow-up study of 208 boys with nonsyndromic bilateral cryptorchidism from our department showed that the boys with gonadotropin insufficiency had an impaired fertility potential after surgery compared to boys with an intact hypothalamus–pituitary–gonadal feedback mechanism.4 In a review from 2022,Hadziselimovic5 suggested that infertility in patients diagnosed with cryptorchid testes is a consequence of a hormonal deficiency rather than temperature-induced cellular damage.展开更多
Background Sperm cryopreservation is widely used in the cattle industry,as it allows for disassociating the localiza-tion of sires and the collection of semen from the timing of artificial insemination.While freeze-th...Background Sperm cryopreservation is widely used in the cattle industry,as it allows for disassociating the localiza-tion of sires and the collection of semen from the timing of artificial insemination.While freeze-thawing is known to impair sperm DNA integrity,whether the damage induced consists of single-(SSB)or double-strand breaks(DSB)has not been determined.In addition,no previous study has addressed if DNA breaks preferentially reside in specific genome regions such as those forming the toroid linker regions,or are rather spread throughout the regions linked to protamines.The main aim of the present work,therefore,was to elucidate the type and localization of the DNA damage generated by cryopreservation and to evaluate its impact on artificial insemination outcomes in cattle.Results The incidence of SSB and DSB was evaluated in 12 ejaculates before and after cryopreservation with the Comet assay,and the localization of the DNA breaks was assessed using pulsed-field gel electrophoresis(PFGE).Before cryopreservation,the incidence of SSB was 10.99%±4.62%and involved 20.56%±3.04%of sperm cells,whereas these figures significantly(P<0.0001)increased up to 34.11%±3.48%and 53.36%±11.00%in frozen-thawed sperm.In contrast,no significant differences in the incidence of DSB were observed(P>0.990)before and after cryopreservation(before:incidence of 13.91%±1.75%of sperm DNA affecting 56.04%±12.49%of sperm cells;after:incidence of 13.55%±1.55%of sperm DNA involving 53.36%±11.00%of sperm cells).Moreover,PFGE revealed that the percentage of sperm DNA fragments whose length was shorter than a toroid(<31.5 kb)was greater(P<0.0001)after(27.00%±4.26%)than before freeze-thawing(15.57%±4.53%).These differences indicated that the DNA breaks induced by cryopreservation affect the regions condensed in protamines,which are structured in toroids.On the other hand,in vivo fertility rates were associated to the incidence of SSB and DSB in frozen-thawed sperm(P=0.032 and P=0.005),but not with the size of the DNA fragments resulting from these breaks(P>0.05).Conclusion Cryopreservation of bovine sperm generates single-strand DNA breaks,which are mainly located in protamine-condensed toroidal regions.The incidence of DNA breaks in cryopreserved sperm has an impact on cat-tle fertility,regardless of the size of generated fragments.展开更多
Aim: To study the association between seminal oxidative stress and human sperm acrosin activity. Methods: It is a prospective study consisting of 30 infertile men and 12 fertile normozoospermic volunteers. A full hist...Aim: To study the association between seminal oxidative stress and human sperm acrosin activity. Methods: It is a prospective study consisting of 30 infertile men and 12 fertile normozoospermic volunteers. A full history, clinical examination and scrotal ultrasound were done to exclude other related factors such as smoking and varicocele. Presence of white blood cells (WBCs) in semen samples was evaluated by peroxidase staining. Lipid peroxidation in spermatozoa was induced after incubating with ferrous sulphate (4 mmol/L) and sodium ascorbate (20 mmol/L). Induced peroxidation of spermatozoa was assessed by determining the production of thiobarbituric acid reactive substances (TBARS). Acrosin activity was measured using the gelatinolysis technique. The halo diameters around the sperm heads and the percentages of spermatozoa showing halo formation were evaluated. An acrosin activity index was calculated by multiplying the halo diameter by the halo formation rate. Results: A significant difference was observed in acrosin activity parameters and TBARS levels between samples with WBCs (>1×106/mL of ejaculate) and those without. This difference was also noted between the normozoospermic and the oligoasthenoteratozoospermic semen samples. The TBARS production by spermatozoa had a significant negative correlation with the acrosin activity index (r = -0.89, P <0.001). Conclusion: The presence of oxidative stress in an individual with leukocytospermia and/or abnormal semen parameters is associated with impaired sperm function as measured by its acrosin activity.展开更多
Cytokines are a heterogeneous group of peptides that play an important role in intercellular communication, regulation of innate and specific immunity, hematopoiesis, interaction between the immune system and neuroend...Cytokines are a heterogeneous group of peptides that play an important role in intercellular communication, regulation of innate and specific immunity, hematopoiesis, interaction between the immune system and neuroendocrine network as well as in reproduction and development. Seminal plasma provides an immunological environ- ment for the semen and contains important biological response mediators. Numerous studies investigated the presence of various cytokines in the seminal plasma and tried to correlate cytokine levels with sperm quality and male fertility. However, the patho- physiological significance of seminal cytokines in sperm function is still not completely understood. The purpose of this review is to provide a brief summary of the extensive literature dealing with cytokines in the seminal plasma and to discuss the contribution of local cytokine immunity to male fertility.展开更多
Objective:To explore the effect of different fertilization time after human chorionic gonadotropin(HCG)injection on the outcome of fertilization in vitro fertilization-embryo transfer(IVF-ET).Methods:One thousand one ...Objective:To explore the effect of different fertilization time after human chorionic gonadotropin(HCG)injection on the outcome of fertilization in vitro fertilization-embryo transfer(IVF-ET).Methods:One thousand one hundred and forty IVF-ET cycles from January 2016 to August 2018 were analyzed retrospectively.According to the different fertilization time after injection of HCG divided into four groups:Group A(38.0 h~39.0 h),Group B(39.1 h~40.0 h),Group C(40.1 h~41.0 h),and Group D(41.1 h~42.0 h).The normal fertilization rate,the normal cleavage rate,the embryo utilization rate,the high-quality embryo rate,the clinical pregnancy rate,the implantation rate,and the spontaneous abortion rate were analyzed among the groups.Then we investigated the effect of different promotion methods on the outcome of fertilization during the optimal fertilization time.Results:There was no significant difference in 2PN cleavage rate,available embryo rate,clinical pregnancy rate,implantation rate and abortion rate among the four groups(P>0.05).The high-quality embryo rate in Group D(44.6%)was the highest,and was significantly different among the four groups(P<0.05).The normal fertilization rate in Group D(71.6%)was the highest,and was significantly different among the four groups(P<0.05).The normal fertilization rate(78.1%)of antagonist group was significantly higher than other groups(P<0.05).Conclusion:The different fertilization time after HCG injection have effects on high-quality embryo rate and normal fertilization rate of patients in IVF-ET.The appropriate fertilization time of patients in IVF-ET was 41 h~42 h after HCG injection in our reproductive center,improved the clinical pregnancy rate and reduced the early abortion rate.The GnRH-ant protocol is superior to other protocol in IVF-ET.展开更多
Objective:To elucidate the relationship among knowledge,attitudes,and practices regarding Covid-19 and their relationship with booster vaccination status among women with infertility.Methods:This questionnaire-based c...Objective:To elucidate the relationship among knowledge,attitudes,and practices regarding Covid-19 and their relationship with booster vaccination status among women with infertility.Methods:This questionnaire-based cross-sectional study was performed online and offline among women with infertility who visited an infertility clinic in Jakarta,Indonesia.We assessed the patient’s knowledge,attitudes,and practices regarding Covid-19 and their relationship with booster vaccination status and sociodemographic profile.Results:A total of 178 subjects participated in this study,and most participants(92.6%)had received booster Covid-19 vaccines.From the questionnaire,74.2%had good knowledge,and 99.4%had good attitudes regarding Covid-19;however,only 57.9%of patients had good practices.A weak positive correlation existed between knowledge and attitudes(r=0.11,P=0.13)and a moderate negative correlation between attitudes and practices(r=-0.44,P=0.56).Participants’knowledge about vaccines and infertility was correlated with booster vaccination status(P=0.04).Academic background(P=0.01)and attitudes(P=0.01)were also correlated with booster vaccination status.The significant determinants of hesitance of receiving Covid-19 booster vaccines were high school education or below(OR=0.08,95%CI 0.02-0.36)and poor practices(OR=0.21,95%CI 0.05-0.95).Conclusions:The majority of the participants had received the Covid-19 booster vaccine and had good knowledge and attitudes but poor practices regarding Covid-19.Most participants had poor knowledge about the relationship between infertility and the Covid-19 vaccine.The general population should be more informed and reminded about practices to prevent Covid-19 and the relationship between vaccination and fertility to increase the number of people who receive Covid-19 booster vaccines.展开更多
Background Despite their low abundance in sperm, mitochondria have diverse functions in this cell type, includ-ing energy production, signalling and calcium regulation. In humans, sperm mitochondrial DNA content(mtDNA...Background Despite their low abundance in sperm, mitochondria have diverse functions in this cell type, includ-ing energy production, signalling and calcium regulation. In humans, sperm mitochondrial DNA content(mtDNAc) has been reported to be negatively linked to sperm function and fertility. Yet, the association between mtDNAc and sperm function in livestock remains unexplored. For this reason, this study aimed to shed some light on the link between mtDNAc and sperm function and fertilising potential in pigs. A qPCR method for mtDNAc quantification was optimised for pig sperm, and the association of this parameter with sperm motility, kinematics, mitochondrial activity, and fertility was subsequently interrogated.Results First, the q PCR method was found to be sensitive and efficient for mtDNAc quantification in pig sperm. By using this technique, mtDNAc was observed to be associated to sperm motility, mitochondrial activity and in vivo, but not in vitro, fertility outcomes. Specifically, sperm with low mtDNAc were seen to exhibit greater motility but decreased mitochondrial activity and intracellular reactive oxygen species. Interestingly, samples with lower mtD-NAc showed higher conception and farrowing rates, but similar in vitro fertilisation rates and embryo development, when compared to those with greater mtDNAc.Conclusions These findings enrich our comprehension of the association of mtDNAc with sperm biology, and lay the foundation for future research into employing this parameter as a molecular predictor for sperm function and fer-tility in livestock.展开更多
Conventional in-vitro fertilization(C-IVF)and intracytoplasmic sperm injection(ICSI)are the two existing insemination methods presently in use in contemporary medically assisted reproduction treatments.While C-IVF ref...Conventional in-vitro fertilization(C-IVF)and intracytoplasmic sperm injection(ICSI)are the two existing insemination methods presently in use in contemporary medically assisted reproduction treatments.While C-IVF refers to co-incubation of a cumulus-oocyte complex(COC)with a certain concentration of sperm suspension,ICSI is defined as the injection of a single spermatozoon directly into the ooplasm of a denuded oocyte.Although the balance of the literature is motivating enough to prefer C-IVF as the insemination method in non-male factor infertility cases,real world data reflect that majority of the practitioners are far from being convinced to do so[1].展开更多
Background Protamination and condensation of sperm chromatin as well as DNA integrity play an essential role during fertilization and embryo development.In some mammals,like pigs,ejaculates are emitted in three separa...Background Protamination and condensation of sperm chromatin as well as DNA integrity play an essential role during fertilization and embryo development.In some mammals,like pigs,ejaculates are emitted in three separate fractions:pre-sperm,sperm-rich(SRF)and post sperm-rich(PSRF).These fractions are known to vary in volume,sperm concentration and quality,as well as in the origin and composition of seminal plasma(SP),with differences being also observed within the SRF one.Yet,whether disparities in the DNA integrity and chromatin condensation and pro-tamination of their sperm exist has not been interrogated.Results This study determined chromatin protamination(Chromomycin A3 test,CMA_(3)),condensation(Dibromobi-mane test,DBB),and DNA integrity(Comet assay)in the pig sperm contained in the first 10 m L of the SRF(SRF-P1),the remaining portion of the sperm-rich fraction(SRF-P2),and the post sperm-rich fraction(PSRF).While chromatin protamination was found to be similar between the different ejaculate fractions(P>0.05),chromatin condensation was seen to be greater in SRF-P1 and SRF-P2 than in the PSRF(P=0.018 and P=0.004,respectively).Regarding DNA integrity,no differences between fractions were observed(P>0.05).As the SRF-P1 has the highest sperm concentra-tion and ejaculate fractions are known to differ in antioxidant composition,the oxidative stress index(OSi)in SP,calcu-lated as total oxidant activity divided by total antioxidant capacity,was tested and confirmed to be higher in the SRF-P1 than in SRF-P2 and PSRF(0.42±0.06 vs.0.23±0.09 and 0.08±0.00,respectively;P<0.01);this index,in addition,was observed to be correlated to the sperm concentration of each fraction(Rs=0.973;P<0.001).Conclusion While sperm DNA integrity was not found to differ between ejaculate fractions,SRF-P1 and SRF-P2 were observed to exhibit greater chromatin condensation than the PSRF.This could be related to the OSi of each fraction.展开更多
The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases(NDs)such as Alzheimer’s disease,Parkinson's disease,or Amyotrophic Lateral Sclerosis.In a process known as‘seedin...The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases(NDs)such as Alzheimer’s disease,Parkinson's disease,or Amyotrophic Lateral Sclerosis.In a process known as‘seeding’,prion-like proteins such as amyloid beta,microtubule-associated protein tau,α-synuclein,silence superoxide dismutase 1,or transactive response DNA-binding protein 43 kDa,propagate their misfolded conformations by transforming their respective soluble monomers into fibrils.Cellular and molecular evidence of prion-like propagation in NDs,the clinical relevance of their‘seeding’capacities,and their levels of contribution towards disease progression have been intensively studied over recent years.This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization,endo-lysosomal leaking,aggregate degradation,and secretion.Debates on the importance of the role of prion-like protein aggregates in NDs,whether causal or consequent,are also discussed.Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.展开更多
OBJECTIVE:To explore the therapeutic efficacy of acupuncture treatment on repeated implantation failure(RIF)patients with cryo-thawed embryo transfer(CET).METHODS:In a retrospective cohort study,all eligible women und...OBJECTIVE:To explore the therapeutic efficacy of acupuncture treatment on repeated implantation failure(RIF)patients with cryo-thawed embryo transfer(CET).METHODS:In a retrospective cohort study,all eligible women undergoing RIF were recruited in our center from January 1,2018 to December 31,2021.The patients were grouped by whether an acceptance of acupuncture treatment before CET,including the acupuncture group(Acu-group,55 cycles)and control group(Con-group,244 cycles).Data were analyzed by using binary logistic regression to explore the relationship of acupuncture treatment with pregnancy outcomes.RESULTS:The Acu-group had higher live-birth rate(LBR)[54.5%vs 41.0%,respectively;odds ratio(OR)=1.105,95%confidence interval(CI)(1.029,1.187),P=0.006]and ongoing pregnancy rate(OPR)[56.4%vs 43.0%,respectively;OR=1.100,95%CI(1.025,1.181),P=0.008]than the Con-group.There were no significant between-group differences in the rates of implantation[OR=1.070,95%CI(0.996,1.149),P=0.064],clinical pregnancy[OR=1.065,95%CI(0.997,1.138),P=0.061],biochemical pregnancy[OR=1.002,95%CI(0.903,1.112),P=0.967],or miscarriage[OR=0.778,95%CI(0.551,1.099),P=0.155].Perinatal outcomes did not differ significantly between the two groups.CONCLUSIONS:Acupuncture treatment could improve the LBR and OPR in RIF patients with CET cycles,suggesting a potential adjuvant therapy of acupuncture to improve the pregnancy outcomes in RIF patients.展开更多
RING finger 187(RNF187),a ubiquitin-ligating(E3)enzyme,plays a crucial role in the proliferation of cancer cells.However,it remains unclear whether RNF187 exhibits comparable functionality in the development of germli...RING finger 187(RNF187),a ubiquitin-ligating(E3)enzyme,plays a crucial role in the proliferation of cancer cells.However,it remains unclear whether RNF187 exhibits comparable functionality in the development of germline cells.To investigate thepotential involvement of RNF187 in germ cell development,we conducted interference and overexpression assays using GC-2 cells,a mouse spermatocyte-derived cell line.Our findings reveal that the interaction between RNF187 and histone H3 increases theviability,proliferation,and migratory capacity of GC-2 cells.Moreover,we provide evidence demonstrating that RNF187 interactswith H3 and mediates the ubiquitination of H3 at lysine 57(K57)or lysine 80(K80),directly or indirectly resulting in increasedcellular transcription.This is a study to report the role of RNF187 in maintaining the development of GC-2 cells by mediatinghistone H3 ubiquitination,thus highlighting the involvement of the K57 and K80 residues of H3 in the epistatic regulation of genetranscription.These discoveries provide a new theoretical foundation for further comprehensive investigations into the functionof RNF187 in the reproductive system.展开更多
This study assessed the feasibility of testis tissue cryopreservation (TTC) for fertility preservation in prepubescent boys with cryptorchidism. From January 2014 to December 2022, the University Hospital of Copenhage...This study assessed the feasibility of testis tissue cryopreservation (TTC) for fertility preservation in prepubescent boys with cryptorchidism. From January 2014 to December 2022, the University Hospital of Copenhagen (Rigshospitalet, Copenhagen, Denmark) implemented TTC for 56 boys with cryptorchidism to preserve their reproductive potential. Testis tissue samples were collected during orchiopexy (32 cases) or at subsequent follow-up procedures (24 cases), necessitated by an increased risk of infertility as indicated by hormonal assessments and/or findings from initial surgical biopsies. Testis samples were procured for TTC and pathological analysis. The cohort had an average age of 1.3 (range: 0.3–3.8) years at the time of orchiopexy, with 91.1% presenting bilateral cryptorchidism. The study revealed a median germ cell count of 0.39 (range: 0–2.88) per seminiferous tubule, with germ cells detected in 98.0% of the bilateral biopsies and 100% of the unilateral, indicating a substantial potential for fertility in these immature tissues. A dark spermatogonia (Ad) was detected in 37 out of 56 patients evaluated, with a median Ad spermatogonia count of 0.027 (range: 0.002–0.158) per seminiferous tubule. A total of 30.2% of the samples lacked Ad spermatogonia, indicative of potential gonadotrophin insufficiency. The median hormone levels measured were as follows: follicle-stimulating hormone (FSH) at 0.69 (range: 0.16–2.5) U l−1, luteinizing hormone (LH) at 0.21 (range: 0.05–3.86) U l−1, and inhibin B at 126 (range: 17–300) pg ml−1. Despite early orchiopexy, 20%–25% of boys with cryptorchidism remain at risk for future infertility, substantiating the necessity of TTC as a precaution. The study highlights the need for refined predictive techniques to identify boys at higher risk of future infertility.展开更多
Oxidative stress is one of the main mechanisms responsible for male infertility.Various conditions such as varicocele,obesity,advanced age,and lifestyle can lead to an increase in reactive oxygen species,causing an ox...Oxidative stress is one of the main mechanisms responsible for male infertility.Various conditions such as varicocele,obesity,advanced age,and lifestyle can lead to an increase in reactive oxygen species,causing an oxidative imbalance in the reproductiveenvironment.Spermatozoa are sensitive to reactive oxygen species and require energy to carry out their main function of fertilizingthe egg.Excessive reactive oxygen species can affect sperm metabolism,leading to immobility,impaired acrosome reaction,and celldeath,thereby impairing reproductive success.This double-blind randomized study evaluated the effect of supplementation withL-carnitine,acetyl-L-carnitine,vitamins,and other nutrients on semen quality in 104 infertile patients with or without varicocele,while also investigating the impact of factors such as obesity and advanced age on treatment.Sperm concentration significantlyincreased in the supplemented group compared to the placebo group(P=0.0186).Total sperm count also significantly increasedin the supplemented group(P=0.0117),as did sperm motility(P=0.0120).The treatment had a positive effect on patients upto 35 years of age in terms of sperm concentration(P=0.0352),while a body mass index(BMI)above 25 kg m^(−2) had a negativeeffect on sperm concentration(P=0.0110).Results were not showing a net benefit in stratifying patients in accordance withtheir BMI since sperm quality increase was not affected by this parameter.In conclusion,antioxidant supplementation may bebeneficial for infertile patients and has a more positive effect on younger patients with a normal weight.展开更多
文摘Objective: Prokineticin-1 (PROK1) is a recently described protein with a wide range of functions including tissue specific angiogenesis, modulation of inflammatory responses and regulation of haematopoiesis. PROK1 has been found in the steroidogenic organs like ovary, testis, adrenal and specially placenta and they have been found to have a role in development of the olfactory system and GnRH system. The aim was to update the role of PROK1 and PROK2 inhuman reproduction since the review was provided by Maldono-Perez (2007) on the potentials of prokineticins in reproduction. Design: A review of international scientific literature by a search of Pubmed and the authors files was done for citation of articles relevant to prokineticins in reproduction, be it its role in ovary, testis, uterus with special emphasis on implantation, normal pregnancy, in labour, pathophysiological states like tubal pregnancy, pcos, various genital tumours, and cases of isolated hypogonadotropic hypogonadism with mutations with PROK2/ PROKR2 and studies detailing functional mechanisms. Results: In the normal cycle, PROK1 has been found to have important roles in implantation, regulating several genes like COX-2, IL-8, IL-11, CTGF related to implantation. Initially murine studies revealed a critical role of PROK2 pathway on olfactory bulb morphogenesis and GnRH secretion which was accidentally discovered and since then several studies on mutations in PROK2/PROKR2 showed that they underlie some case of KS in humans. Although in mouse heterozygote state is not associated with clinical phenotype, most of human mutations are heterozygous. Conclusions: Role of PROK-1 in the process of implantation, with a deeper understanding of the process success rates in IVF and ART can be improved, besides understanding the pathophysiology of tubal pregnancy. Further presence in ovarian follicles of PROK1 can be used to plan a strategy for treating pcos. Development of antagonism of PROK’S may be a helpful strategy in treating preterm labour.
文摘Background: In Vitro Fertilization/Intracytoplasmic Sperm Injection (IVF/ICSI) represents the final step in the management of Polycystic Ovarian Syndrome (PCOS). Our objective was to study the association between PCOS phenotypes and IVF/ICSI results in women admitted to Gynaecological Endoscopic Surgery and Human Reproductive Teaching Hospital (CHRACERH). Material and Method: We carried out a cohort study with historical-prospective data collection over a period of seven years (January 2016 to March 2023) at Chracerh. PCOS patients were subdivided into 4 subgroups A, B, C and D. Results: We recruited 128 patients including 64 PCOS patients divided into four phenotypes and 64 non-PCOS patients constituting the control group. Phenotype D without hyperandrogenism had used the lowest dose of gonadotropins, i.e. 1939.7 ± 454.3 IU, and had produced a greater quantity of estradiol on the day ovulation was triggered (6529.8 ± 4324.8 ng/ml). The average number of punctured follicles and mature oocytes were higher in the phenotype D group. Ovarian hyperstimulation syndrome (OHSS) occurred mainly in phenotype D (3/35), with an estimated prevalence of 2.3%. The fertilization rate seemed lower in the hyperandrogenic phenotypes A, B, C compared to the group without hyperandrogenism without significant difference (p = 0.461). The biological pregnancy rate and live birth rate were comparable between the different groups. Conclusion: Phenotype D used less dose of gonadotropins. Biological pregnancy and live birth rates were comparable between the different phenotypes.
文摘Background: Since 2021, high-risk Human Papilloma Virus (HR-HPV) testing has been the recommended screening test for cervical cancer for all settings;either used alone in a “test and treat” strategy, or with a triage test, with or without biopsy, before treatment. Cameroon has rolled out immunization against HPV 16 and 18, but studies show a higher prevalence of non-16/18 HR-HPV types. Objectives: Determine the prevalence of precancerous lesions, in women with HR-HPV infection and evaluate association of digital cervicography (DC) VIA/VILI positivity with HPV serotype, as a measure of their contribution to precancer and cancer incidence. Methodology: The study was cross-sectional, descriptive, and analytic. It took place at the Etoug-Ebe and Ekoudoum Baptist Hospitals in Yaoundé, during the period April-September 2022. We reviewed the records of women screened for cervical cancer between February 2020 and December 2021 and evaluated the prevalence of lesions on digital cervicography (DC) with VIA/VILI for women positive for HR-HPV serotypes. The data were analyzed using SPSS version 20.0 for Windows. P values Results: We identified 315 cases with a positive HR-HPV deoxyribonucleic acid (DNA) test, 224 (71.1%) had a DC VIA/VILI triage test done. Of these, 30 (13.4%) women had a positive DC VIA/VILI, with five women (2.2%) having lesions suggestive of cancer. Out of 11 cases positive for HPV 16 alone, 05 (45.5%) had a positive DC VIA/VILI test. Of the 14 cases positive for HPV 18 alone, 03 (21.4%) had a positive VIA/VILI, meanwhile only 19 (10.7%) of the 177 cases positive for non-16/18 HPV had a positive VIA/VILI test. Conclusion: A high proportion of women (13.4%) with HR HPV had a positive DC VIA/VILI, with a significant proportion (2.2%) having lesions suggestive of invasive cervical cancer HR-HPV serotype was associated with DC VIA/VILI positivity;HPV 16 had the strongest association (45.5%), followed by HPV 18 (21.4%), and non-16/18 HR-HPV (10.7%), suggesting a decreasing order of oncogenicity.
基金supported by the grants from the National Nature Science Foundation of China(No.32170862)Major Scientific and Technological Projects for Collaborative Prevention and Control of Birth Defect in Hunan Province(No.2019SK1012)+1 种基金the Research Team for Reproduction Health and Translational Medicine of Hunan Normal University(No.2023JC101)Graduate Scientific Research Innovation Project of Hunan Province,China(No.CX2022520).
文摘Infertility has become one of the most serious diseases worldwide,and 50% of this disease can be attributed to male-related factors.Spermatogenesis,by definition,is a complex process by which spermatogonial stem cells(SSCs)self-renew to maintain stem cell population within the testes and differentiate into mature spermatids.It is of great significance to uncover gene regulation and signaling pathways that are involved in the fate determinations of SSCs with aims to better understand molecular mechanisms underlying human spermatogenesis and identify novel targets for gene therapy of male infertility.Significant achievement has recently been made in demonstrating the signaling molecules and pathways mediating the fate decisions of mammalian SSCs.In this review,we address key gene regulation and crucial signaling transduction pathways in controlling the self-renewal,differentiation,and apoptosis of SSCs,and we illustrate the networks of genes and signaling pathways in SSC fate determinations.We also highlight perspectives and future directions in SSC regulation by genes and their signaling pathways.This review could provide novel insights into the genetic regulation of normal and abnormal spermatogenesis and offer molecular targets to develop new approaches for gene therapy of male infertility.
文摘Azoospermia, defined as a complete absence of spermatozoa in the ejaculate, is a relatively common condition among infertile men. Establishing the etiological diagnosis can be challenging and often requires various investigations. This cross-sectional study, conducted in Cotonou among 35 azoospermic men, aimed to assess the role of biochemical analysis of seminal fluid in determining the etiological diagnosis. The results revealed significant heterogeneity in biochemical profiles. Most of the patients had normal levels of alpha-glucosidase, fructose, and zinc, indicating normal accessory gland function and suggesting non-obstructive azoospermia. However, a significant subgroup exhibited abnormalities in these markers, suggesting a possible obstructive azoospermia. The heterogeneity in biochemical profiles observed in this study highlights the need for further studies to better characterize azoospermia in Benin.
基金supported by the grants from the National Natural Science Foundation of China to Zhi-Ying Wu(82230062,Beijing),Qiao Wei(82402156,Beijing),and Wanzhong Ge(31970668,Beijing)the research foundation for distinguished scholar of Zhejiang University(188020-193810101/089,Hangzhou)to Zhi-Ying Wu
文摘Hereditary spastic paraplegias(HSPs)refer to a genetically and clinically heterogeneous group of neurodegenerative disorders characterized by the degeneration of motor neurons.To date,a significant number of patients still have not received a definite genetic diagnosis.Therefore,identifying unreported causative genes continues to be of great importance.Here,we perform whole-exome sequencing in a cohort of Chinese HSP patients.Three homozygous variants(p.L604W,p.S517F,and p.T984A)within the sterol regulatory element-binding factor 2(SREBF2)gene are identified in one autosomal recessive family and two sporadic patients,respectively.Co-segregation is confirmed by Sanger sequencing in all available members.The three variants are rare in the public or in-house database and are predicted to be damaging.The biological impacts of variants in SREBF2 are examined by functional experiments in patient-derived fibroblasts and Drosophila.We find that the variants upregulate cellular cholesterol due to the overactivation of SREBP2,eventually impairing the autophagosomal and lysosomal functions.The overexpression of the mature form of SREBP2 leads to locomotion defects in Drosophila.Our findings identify SREBF2 as a causative gene for HSP and highlight the impairment of cholesterol as a critical pathway for HSP.
文摘Dear Editor,We are much obliged that Hadziselimovic1 has used our data2 to highlight the substantial proportion of boys with cryptorchidism where gonadotropin insufficiency is an important factor related to the pathogenesis.We have recently presented a study on a series of 453 consecutive boys with bilateral nonsyndromic cryptorchidism,in which we conducted hormonal evaluations and assessed germ cell numbers in testicular biopsies.3 In this series,45%of the boys were classified as having gonadotropin insufficiency.3 Identifying these patients at the time of surgery is important.A recent follow-up study of 208 boys with nonsyndromic bilateral cryptorchidism from our department showed that the boys with gonadotropin insufficiency had an impaired fertility potential after surgery compared to boys with an intact hypothalamus–pituitary–gonadal feedback mechanism.4 In a review from 2022,Hadziselimovic5 suggested that infertility in patients diagnosed with cryptorchid testes is a consequence of a hormonal deficiency rather than temperature-induced cellular damage.
基金Ministry of Science,Innovation and Universities,Spain(NextGeneration EU fundsMaría Zambrano Program 124/MTAI/22+2 种基金and PID2020-113320RB-I00)Agency for Management of University and Research Grants,Regional Government of Catalonia,Spain(2021-SGR-00900)Catalan Institution for Research and Advanced Studies(ICREA).
文摘Background Sperm cryopreservation is widely used in the cattle industry,as it allows for disassociating the localiza-tion of sires and the collection of semen from the timing of artificial insemination.While freeze-thawing is known to impair sperm DNA integrity,whether the damage induced consists of single-(SSB)or double-strand breaks(DSB)has not been determined.In addition,no previous study has addressed if DNA breaks preferentially reside in specific genome regions such as those forming the toroid linker regions,or are rather spread throughout the regions linked to protamines.The main aim of the present work,therefore,was to elucidate the type and localization of the DNA damage generated by cryopreservation and to evaluate its impact on artificial insemination outcomes in cattle.Results The incidence of SSB and DSB was evaluated in 12 ejaculates before and after cryopreservation with the Comet assay,and the localization of the DNA breaks was assessed using pulsed-field gel electrophoresis(PFGE).Before cryopreservation,the incidence of SSB was 10.99%±4.62%and involved 20.56%±3.04%of sperm cells,whereas these figures significantly(P<0.0001)increased up to 34.11%±3.48%and 53.36%±11.00%in frozen-thawed sperm.In contrast,no significant differences in the incidence of DSB were observed(P>0.990)before and after cryopreservation(before:incidence of 13.91%±1.75%of sperm DNA affecting 56.04%±12.49%of sperm cells;after:incidence of 13.55%±1.55%of sperm DNA involving 53.36%±11.00%of sperm cells).Moreover,PFGE revealed that the percentage of sperm DNA fragments whose length was shorter than a toroid(<31.5 kb)was greater(P<0.0001)after(27.00%±4.26%)than before freeze-thawing(15.57%±4.53%).These differences indicated that the DNA breaks induced by cryopreservation affect the regions condensed in protamines,which are structured in toroids.On the other hand,in vivo fertility rates were associated to the incidence of SSB and DSB in frozen-thawed sperm(P=0.032 and P=0.005),but not with the size of the DNA fragments resulting from these breaks(P>0.05).Conclusion Cryopreservation of bovine sperm generates single-strand DNA breaks,which are mainly located in protamine-condensed toroidal regions.The incidence of DNA breaks in cryopreserved sperm has an impact on cat-tle fertility,regardless of the size of generated fragments.
文摘Aim: To study the association between seminal oxidative stress and human sperm acrosin activity. Methods: It is a prospective study consisting of 30 infertile men and 12 fertile normozoospermic volunteers. A full history, clinical examination and scrotal ultrasound were done to exclude other related factors such as smoking and varicocele. Presence of white blood cells (WBCs) in semen samples was evaluated by peroxidase staining. Lipid peroxidation in spermatozoa was induced after incubating with ferrous sulphate (4 mmol/L) and sodium ascorbate (20 mmol/L). Induced peroxidation of spermatozoa was assessed by determining the production of thiobarbituric acid reactive substances (TBARS). Acrosin activity was measured using the gelatinolysis technique. The halo diameters around the sperm heads and the percentages of spermatozoa showing halo formation were evaluated. An acrosin activity index was calculated by multiplying the halo diameter by the halo formation rate. Results: A significant difference was observed in acrosin activity parameters and TBARS levels between samples with WBCs (>1×106/mL of ejaculate) and those without. This difference was also noted between the normozoospermic and the oligoasthenoteratozoospermic semen samples. The TBARS production by spermatozoa had a significant negative correlation with the acrosin activity index (r = -0.89, P <0.001). Conclusion: The presence of oxidative stress in an individual with leukocytospermia and/or abnormal semen parameters is associated with impaired sperm function as measured by its acrosin activity.
文摘Cytokines are a heterogeneous group of peptides that play an important role in intercellular communication, regulation of innate and specific immunity, hematopoiesis, interaction between the immune system and neuroendocrine network as well as in reproduction and development. Seminal plasma provides an immunological environ- ment for the semen and contains important biological response mediators. Numerous studies investigated the presence of various cytokines in the seminal plasma and tried to correlate cytokine levels with sperm quality and male fertility. However, the patho- physiological significance of seminal cytokines in sperm function is still not completely understood. The purpose of this review is to provide a brief summary of the extensive literature dealing with cytokines in the seminal plasma and to discuss the contribution of local cytokine immunity to male fertility.
基金National Natural Science Foundation of China(No.81460236)Major Science and Technology Program of Hainan Province(No.ZDKJ2017007)Innovative Project for Postgraduate of Hainan Province(No.Hys2018-281)。
文摘Objective:To explore the effect of different fertilization time after human chorionic gonadotropin(HCG)injection on the outcome of fertilization in vitro fertilization-embryo transfer(IVF-ET).Methods:One thousand one hundred and forty IVF-ET cycles from January 2016 to August 2018 were analyzed retrospectively.According to the different fertilization time after injection of HCG divided into four groups:Group A(38.0 h~39.0 h),Group B(39.1 h~40.0 h),Group C(40.1 h~41.0 h),and Group D(41.1 h~42.0 h).The normal fertilization rate,the normal cleavage rate,the embryo utilization rate,the high-quality embryo rate,the clinical pregnancy rate,the implantation rate,and the spontaneous abortion rate were analyzed among the groups.Then we investigated the effect of different promotion methods on the outcome of fertilization during the optimal fertilization time.Results:There was no significant difference in 2PN cleavage rate,available embryo rate,clinical pregnancy rate,implantation rate and abortion rate among the four groups(P>0.05).The high-quality embryo rate in Group D(44.6%)was the highest,and was significantly different among the four groups(P<0.05).The normal fertilization rate in Group D(71.6%)was the highest,and was significantly different among the four groups(P<0.05).The normal fertilization rate(78.1%)of antagonist group was significantly higher than other groups(P<0.05).Conclusion:The different fertilization time after HCG injection have effects on high-quality embryo rate and normal fertilization rate of patients in IVF-ET.The appropriate fertilization time of patients in IVF-ET was 41 h~42 h after HCG injection in our reproductive center,improved the clinical pregnancy rate and reduced the early abortion rate.The GnRH-ant protocol is superior to other protocol in IVF-ET.
文摘Objective:To elucidate the relationship among knowledge,attitudes,and practices regarding Covid-19 and their relationship with booster vaccination status among women with infertility.Methods:This questionnaire-based cross-sectional study was performed online and offline among women with infertility who visited an infertility clinic in Jakarta,Indonesia.We assessed the patient’s knowledge,attitudes,and practices regarding Covid-19 and their relationship with booster vaccination status and sociodemographic profile.Results:A total of 178 subjects participated in this study,and most participants(92.6%)had received booster Covid-19 vaccines.From the questionnaire,74.2%had good knowledge,and 99.4%had good attitudes regarding Covid-19;however,only 57.9%of patients had good practices.A weak positive correlation existed between knowledge and attitudes(r=0.11,P=0.13)and a moderate negative correlation between attitudes and practices(r=-0.44,P=0.56).Participants’knowledge about vaccines and infertility was correlated with booster vaccination status(P=0.04).Academic background(P=0.01)and attitudes(P=0.01)were also correlated with booster vaccination status.The significant determinants of hesitance of receiving Covid-19 booster vaccines were high school education or below(OR=0.08,95%CI 0.02-0.36)and poor practices(OR=0.21,95%CI 0.05-0.95).Conclusions:The majority of the participants had received the Covid-19 booster vaccine and had good knowledge and attitudes but poor practices regarding Covid-19.Most participants had poor knowledge about the relationship between infertility and the Covid-19 vaccine.The general population should be more informed and reminded about practices to prevent Covid-19 and the relationship between vaccination and fertility to increase the number of people who receive Covid-19 booster vaccines.
基金funded by the Ministry of Science and Innovation,Spain (AGL2017-88329-R, FPU18/00666 and PID2020-113320RB-I00)the Regional Government of Catalonia,Spain (2017-SGR-1229, 2020-FI-B-00412 and 2020-SGR-0900)the Catalan Institution for Research and Advanced Studies (ICREA)。
文摘Background Despite their low abundance in sperm, mitochondria have diverse functions in this cell type, includ-ing energy production, signalling and calcium regulation. In humans, sperm mitochondrial DNA content(mtDNAc) has been reported to be negatively linked to sperm function and fertility. Yet, the association between mtDNAc and sperm function in livestock remains unexplored. For this reason, this study aimed to shed some light on the link between mtDNAc and sperm function and fertilising potential in pigs. A qPCR method for mtDNAc quantification was optimised for pig sperm, and the association of this parameter with sperm motility, kinematics, mitochondrial activity, and fertility was subsequently interrogated.Results First, the q PCR method was found to be sensitive and efficient for mtDNAc quantification in pig sperm. By using this technique, mtDNAc was observed to be associated to sperm motility, mitochondrial activity and in vivo, but not in vitro, fertility outcomes. Specifically, sperm with low mtDNAc were seen to exhibit greater motility but decreased mitochondrial activity and intracellular reactive oxygen species. Interestingly, samples with lower mtD-NAc showed higher conception and farrowing rates, but similar in vitro fertilisation rates and embryo development, when compared to those with greater mtDNAc.Conclusions These findings enrich our comprehension of the association of mtDNAc with sperm biology, and lay the foundation for future research into employing this parameter as a molecular predictor for sperm function and fer-tility in livestock.
文摘Conventional in-vitro fertilization(C-IVF)and intracytoplasmic sperm injection(ICSI)are the two existing insemination methods presently in use in contemporary medically assisted reproduction treatments.While C-IVF refers to co-incubation of a cumulus-oocyte complex(COC)with a certain concentration of sperm suspension,ICSI is defined as the injection of a single spermatozoon directly into the ooplasm of a denuded oocyte.Although the balance of the literature is motivating enough to prefer C-IVF as the insemination method in non-male factor infertility cases,real world data reflect that majority of the practitioners are far from being convinced to do so[1].
基金This research was supported by the European Union’s Horizon 2020 research and innovation scheme under the Marie Skłodowska-Curie grant agreement No.801342(Tecniospring INDUSTRYGrant:TECSPR-19-1-0003)+4 种基金the Ministry of Science and Innovation,Spain(Grants:PID2020-113320RB-I00,PID2020-113493RB-I00,RYC2021-034546-I and RYC2021-034764-I)the Catalan Agency for Management of University and Research Grants,Regional Government of Catalonia,Spain(Grants:2017-SGR-1229 and 2021-SGR-00900)the Seneca Foundation,Regional Government of Murcia,Spain(Grant:21935/PI/22)La Marato de TV3 Foundation(Grant:214/857-202039)and the Catalan Institution for Research and Advanced Studies(ICREA).
文摘Background Protamination and condensation of sperm chromatin as well as DNA integrity play an essential role during fertilization and embryo development.In some mammals,like pigs,ejaculates are emitted in three separate fractions:pre-sperm,sperm-rich(SRF)and post sperm-rich(PSRF).These fractions are known to vary in volume,sperm concentration and quality,as well as in the origin and composition of seminal plasma(SP),with differences being also observed within the SRF one.Yet,whether disparities in the DNA integrity and chromatin condensation and pro-tamination of their sperm exist has not been interrogated.Results This study determined chromatin protamination(Chromomycin A3 test,CMA_(3)),condensation(Dibromobi-mane test,DBB),and DNA integrity(Comet assay)in the pig sperm contained in the first 10 m L of the SRF(SRF-P1),the remaining portion of the sperm-rich fraction(SRF-P2),and the post sperm-rich fraction(PSRF).While chromatin protamination was found to be similar between the different ejaculate fractions(P>0.05),chromatin condensation was seen to be greater in SRF-P1 and SRF-P2 than in the PSRF(P=0.018 and P=0.004,respectively).Regarding DNA integrity,no differences between fractions were observed(P>0.05).As the SRF-P1 has the highest sperm concentra-tion and ejaculate fractions are known to differ in antioxidant composition,the oxidative stress index(OSi)in SP,calcu-lated as total oxidant activity divided by total antioxidant capacity,was tested and confirmed to be higher in the SRF-P1 than in SRF-P2 and PSRF(0.42±0.06 vs.0.23±0.09 and 0.08±0.00,respectively;P<0.01);this index,in addition,was observed to be correlated to the sperm concentration of each fraction(Rs=0.973;P<0.001).Conclusion While sperm DNA integrity was not found to differ between ejaculate fractions,SRF-P1 and SRF-P2 were observed to exhibit greater chromatin condensation than the PSRF.This could be related to the OSi of each fraction.
基金supported by the National Natural Science Foundation of China(82071424)the Zhejiang University Education Foundation Global Partnership Fund(188170+194452115/011).
文摘The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases(NDs)such as Alzheimer’s disease,Parkinson's disease,or Amyotrophic Lateral Sclerosis.In a process known as‘seeding’,prion-like proteins such as amyloid beta,microtubule-associated protein tau,α-synuclein,silence superoxide dismutase 1,or transactive response DNA-binding protein 43 kDa,propagate their misfolded conformations by transforming their respective soluble monomers into fibrils.Cellular and molecular evidence of prion-like propagation in NDs,the clinical relevance of their‘seeding’capacities,and their levels of contribution towards disease progression have been intensively studied over recent years.This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization,endo-lysosomal leaking,aggregate degradation,and secretion.Debates on the importance of the role of prion-like protein aggregates in NDs,whether causal or consequent,are also discussed.Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.
文摘OBJECTIVE:To explore the therapeutic efficacy of acupuncture treatment on repeated implantation failure(RIF)patients with cryo-thawed embryo transfer(CET).METHODS:In a retrospective cohort study,all eligible women undergoing RIF were recruited in our center from January 1,2018 to December 31,2021.The patients were grouped by whether an acceptance of acupuncture treatment before CET,including the acupuncture group(Acu-group,55 cycles)and control group(Con-group,244 cycles).Data were analyzed by using binary logistic regression to explore the relationship of acupuncture treatment with pregnancy outcomes.RESULTS:The Acu-group had higher live-birth rate(LBR)[54.5%vs 41.0%,respectively;odds ratio(OR)=1.105,95%confidence interval(CI)(1.029,1.187),P=0.006]and ongoing pregnancy rate(OPR)[56.4%vs 43.0%,respectively;OR=1.100,95%CI(1.025,1.181),P=0.008]than the Con-group.There were no significant between-group differences in the rates of implantation[OR=1.070,95%CI(0.996,1.149),P=0.064],clinical pregnancy[OR=1.065,95%CI(0.997,1.138),P=0.061],biochemical pregnancy[OR=1.002,95%CI(0.903,1.112),P=0.967],or miscarriage[OR=0.778,95%CI(0.551,1.099),P=0.155].Perinatal outcomes did not differ significantly between the two groups.CONCLUSIONS:Acupuncture treatment could improve the LBR and OPR in RIF patients with CET cycles,suggesting a potential adjuvant therapy of acupuncture to improve the pregnancy outcomes in RIF patients.
基金supported by the National Natural Science Foundation ofChina(82271633 to BZ and 82201762 to TTG)the Gusu Health Talent Programof Suzhou(GSWS2020068 to BZ)+2 种基金the Top Talent Support Program for Youngand Middle-aged People of Wuxi Health Committee(BJ2020047 to YBW)theScience and Technology Project of Changzhou(CJ20220143 to TTG)the Changzhou Health Committee Funded Young Investigator Training Project(CZQM2020099 to TTG)。
文摘RING finger 187(RNF187),a ubiquitin-ligating(E3)enzyme,plays a crucial role in the proliferation of cancer cells.However,it remains unclear whether RNF187 exhibits comparable functionality in the development of germline cells.To investigate thepotential involvement of RNF187 in germ cell development,we conducted interference and overexpression assays using GC-2 cells,a mouse spermatocyte-derived cell line.Our findings reveal that the interaction between RNF187 and histone H3 increases theviability,proliferation,and migratory capacity of GC-2 cells.Moreover,we provide evidence demonstrating that RNF187 interactswith H3 and mediates the ubiquitination of H3 at lysine 57(K57)or lysine 80(K80),directly or indirectly resulting in increasedcellular transcription.This is a study to report the role of RNF187 in maintaining the development of GC-2 cells by mediatinghistone H3 ubiquitination,thus highlighting the involvement of the K57 and K80 residues of H3 in the epistatic regulation of genetranscription.These discoveries provide a new theoretical foundation for further comprehensive investigations into the functionof RNF187 in the reproductive system.
基金financially supported by the University Hospital of Copenhagen,Rigshospitalet,the Danish Child Cancer Foundation(2021-7395)Vissing Fonden(519140 AHO/PPT)the Research Fund between Rigshospitalet and Odense University Hospital(136-A5544).
文摘This study assessed the feasibility of testis tissue cryopreservation (TTC) for fertility preservation in prepubescent boys with cryptorchidism. From January 2014 to December 2022, the University Hospital of Copenhagen (Rigshospitalet, Copenhagen, Denmark) implemented TTC for 56 boys with cryptorchidism to preserve their reproductive potential. Testis tissue samples were collected during orchiopexy (32 cases) or at subsequent follow-up procedures (24 cases), necessitated by an increased risk of infertility as indicated by hormonal assessments and/or findings from initial surgical biopsies. Testis samples were procured for TTC and pathological analysis. The cohort had an average age of 1.3 (range: 0.3–3.8) years at the time of orchiopexy, with 91.1% presenting bilateral cryptorchidism. The study revealed a median germ cell count of 0.39 (range: 0–2.88) per seminiferous tubule, with germ cells detected in 98.0% of the bilateral biopsies and 100% of the unilateral, indicating a substantial potential for fertility in these immature tissues. A dark spermatogonia (Ad) was detected in 37 out of 56 patients evaluated, with a median Ad spermatogonia count of 0.027 (range: 0.002–0.158) per seminiferous tubule. A total of 30.2% of the samples lacked Ad spermatogonia, indicative of potential gonadotrophin insufficiency. The median hormone levels measured were as follows: follicle-stimulating hormone (FSH) at 0.69 (range: 0.16–2.5) U l−1, luteinizing hormone (LH) at 0.21 (range: 0.05–3.86) U l−1, and inhibin B at 126 (range: 17–300) pg ml−1. Despite early orchiopexy, 20%–25% of boys with cryptorchidism remain at risk for future infertility, substantiating the necessity of TTC as a precaution. The study highlights the need for refined predictive techniques to identify boys at higher risk of future infertility.
文摘Oxidative stress is one of the main mechanisms responsible for male infertility.Various conditions such as varicocele,obesity,advanced age,and lifestyle can lead to an increase in reactive oxygen species,causing an oxidative imbalance in the reproductiveenvironment.Spermatozoa are sensitive to reactive oxygen species and require energy to carry out their main function of fertilizingthe egg.Excessive reactive oxygen species can affect sperm metabolism,leading to immobility,impaired acrosome reaction,and celldeath,thereby impairing reproductive success.This double-blind randomized study evaluated the effect of supplementation withL-carnitine,acetyl-L-carnitine,vitamins,and other nutrients on semen quality in 104 infertile patients with or without varicocele,while also investigating the impact of factors such as obesity and advanced age on treatment.Sperm concentration significantlyincreased in the supplemented group compared to the placebo group(P=0.0186).Total sperm count also significantly increasedin the supplemented group(P=0.0117),as did sperm motility(P=0.0120).The treatment had a positive effect on patients upto 35 years of age in terms of sperm concentration(P=0.0352),while a body mass index(BMI)above 25 kg m^(−2) had a negativeeffect on sperm concentration(P=0.0110).Results were not showing a net benefit in stratifying patients in accordance withtheir BMI since sperm quality increase was not affected by this parameter.In conclusion,antioxidant supplementation may bebeneficial for infertile patients and has a more positive effect on younger patients with a normal weight.
