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
Grooming,as an evolutionarily conserved repetitive behavior,is common in various animals,including humans,and serves essential functions including,but not limited to,hygiene maintenance,thermoregulation,de-arousal,str...Grooming,as an evolutionarily conserved repetitive behavior,is common in various animals,including humans,and serves essential functions including,but not limited to,hygiene maintenance,thermoregulation,de-arousal,stress reduction,and social behaviors.In rodents,grooming involves a patterned and sequenced structure,known as the syntactic chain with four phases that comprise repeated stereotyped movements happening in a cephalocaudal progression style,beginning from the nose to the face,to the head,and finally ending with body licking.The context-dependent occurrence of grooming behavior indicates its adaptive significance.This review briefly summarizes the neural substrates responsible for rodent grooming behavior and explores its relevance in rodent models of neuropsychiatric disorders and neurodegenerative diseases with aberrant grooming phenotypes.We further emphasize the utility of rodent grooming as a reliable measure of repetitive behavior in neuropsychiatric models,holding promise for translational psychiatry.Herein,we mainly focus on rodent self-grooming.Allogrooming(grooming being applied on one animal by its conspecifics via licking or carefully nibbling)and heterogrooming(a form of grooming behavior directing towards another animal,which occurs in other contexts,such as maternal,sexual,aggressive,or social behaviors)are not covered due to space constraints.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
This study aimed to ascertain the current status of Japanese sperm banking for young cancer patients. During 2015, we mailed the directors of 695 institutes where sperm cryopreservation might be performed with questio...This study aimed to ascertain the current status of Japanese sperm banking for young cancer patients. During 2015, we mailed the directors of 695 institutes where sperm cryopreservation might be performed with questionnaires requesting information on the number of patients, age, precryopreservation chemotherapy, semen analyses results and diagnoses, cryopreservation success rate, and causes of unsuccessful cryopreservation. Of these 695 institutes, 92 had cryopreserved sperm before chemotherapy within the study period. In all, 820 cancer patients （237 testicular, 383 hematological, 46 bone and soft tissue, 20 brain, and 134 other malignancy） consulted the responding institutes for sperm cryopreservation. Except for testicular tumor, the number of patients whose sperm was preserved before cancer treatment was low compared to that of young cancer patients. Approximately 20% of patients with malignancies other than testicular tumor underwent chemotherapy before cryopreservation. The success rate of cryopreservation in hematological malignancy was 82.5%, significantly lower than that of both the testicular cancer （93.6%） and other malignancy groups （95.6%） （P 〈 0.05）. The primary reasons for preservation failure were azoospermia and poor semen quality. Patients with hematological malignancies had a higher rate of unsuccessful cryopreservation compared to those in other groups, possibly due to the large number of patients requesting sperm cryopreservation after chemotherapy induction. In Japan, information regarding sperm banking prior to cancer treatment appears to be lacking. Information regarding sperm preservation before chemotherapy should be provided to all Japanese oncologists.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
Objective To investigate the relationship and potential pathways between metal(loid)exposure and the risk of polycystic ovary syndrome(PCOS)in women of childbearing age.Methods This case-control study included 200 pat...Objective To investigate the relationship and potential pathways between metal(loid)exposure and the risk of polycystic ovary syndrome(PCOS)in women of childbearing age.Methods This case-control study included 200 patients with PCOS(cases)and 896 non-PCOS controls with the age of 25-37 years.The concentrations of 29 metal(loid)s in the follicular fluid(FF)and clinical indicators in the serum were measured in all participants.Logistic regression analysis and mediation analysis were conducted to evaluate the associations between metal(loid)exposure and PCOS risk and investigate the possible roles of clinical indicators,respectively.Results Logistic regression analysis revealed an association between high copper levels in FF and increased PCOS risk(highest vs.lowest quartile:adjusted odds ratio=2.94,95%confidence interval:1.83-4.72).A high luteinizing hormone/follicle-stimulating hormone ratio and elevated levels of testosterone and anti-Müllerian hormone(AMH)were strongly associated with increased PCOS risk induced by high copper exposure.The mediation analysis indicated a mediating effect of AMH in the association between copper exposure and PCOS risk.Conclusion Copper may affect PCOS risk through the hypothalamic-pituitary-ovarian axis,mediated by AMH.Copper exposure and internal AMH levels are important indicators for early warning of PCOS development.展开更多
Spermatogenesis is a sophisticated biological process by which spermatogonial stem cells(SSCs)undergo self-renewal and differentiation into spermatozoa.Molecular mechanisms underlying fate determinations of human SSCs...Spermatogenesis is a sophisticated biological process by which spermatogonial stem cells(SSCs)undergo self-renewal and differentiation into spermatozoa.Molecular mechanisms underlying fate determinations of human SSCs by key genes and signaling pathways remain elusive.Here,we report for the first time that Yes1-associated transcriptional regulator(YAP1)is required for fate determinations of SSCs and male fertility by interacting with RAD21 and targeting NEDD4 in humans and mice.YAP1 was mainly located at cell nuclei of human SSCs.YAP1 silencing resulted in the decreases in proliferation and DNA synthesis as well as an enhancement in apoptosis of human SSCs both in vivo and in vitro.RNA sequencing and real-time polymerase chain reaction assays identified NEDD4 as a target of YAP1,and NEDD4 knockdown inhibited the proliferation of human SSCs and increased their apoptosis.Furthermore,YAP1 interacted with RAD21 to regulate NEDD4 transcription in human SSCs.Importantly,YAP1 abnormalities were found to be associated with non-obstructive azoospermia(NOA)as manifested as lower expression level of YAP1 in testicular tissues of NOA patients and YAP1 single-nucleotide variants(SNVs)in 777 NOA patients.Finally,Yap1 germline conditional knockout(cKO)mice assumed mitotic arrest,low sperm count,and motility.Collectively,these results highlight a critical role of YAP1 in determining the fate determinations of human SSCs and male infertility through the YAP1/RAD21/NEDD4 pathway.This study provides new insights into the genetic regulatory mechanisms underlying human spermatogenesis and the pathogenesis of NOA,and it offers new targets for gene therapy of male infertility.展开更多
Aim： To determine the possible roles of the t-complex testis expressed gene 5 （Tctex5） on sperm functions, the fulllength sequence of mRNA was studied and compared in the testis between the normal wild-type and the...Aim： To determine the possible roles of the t-complex testis expressed gene 5 （Tctex5） on sperm functions, the fulllength sequence of mRNA was studied and compared in the testis between the normal wild-type and the sterile t-haplotype mutant mice. Methods： We applied rapid amplification of cDNA ends, Northern blot and reverse transcription polymerase chain reaction to analyze the full length of Tctex5 mRNAs isolated from testes of the wild-type and the t-haplotype mice. Reverse transcription polymerase chain reaction was used to semi-quantitatively compare expression of Tctex5 transcripts in the 16 tissues and 9.5 day stage embryos in the wild-type mice. E-translation was applied to estimate the amino acid sequences. Results： One long and one short transcript of Tctex5 mRNA were discovered in mouse testis of wild-type （Tctex5^long-＋ and Tctex5^short-＋） and t-haplotype （Tctex5^long-＋ and Tctex5^short-＋） mice, respectively. Being enhanced only in the testis, Tctex5^long-＋ had 17 point mutations and one 15-bp-deletion in the exon 1 region, comparing with the Tctex5^long-＋, whereas the Tctex5^short-＋ was similar to the Tctex5^short-＋. The short isoforms of Tctex5 mRNAs in the two models encoded exactly the same peptides, but the long isoforms did not. The estimated peptide encoded by Tctex5^long-＋ had significant mutations on putative sites of phosphorylation and PP1 binding. Conclusion： We established that mutations that occur in the Tctex5 long transcript of the t-haplotype mice are important for normal sperm function, whereas the short transcript of Tctex5 might have a conserved function among different tissues. （Asian J Androl 2008 Mar; 10： 219-226）展开更多
This paper aims to determine the possible role of estrogen receptor-β （ERβ） gene Rsal polymorphism on sperm fertility and early embryonic development in humans. Three groups of Chinese men were recruited： in vitr...This paper aims to determine the possible role of estrogen receptor-β （ERβ） gene Rsal polymorphism on sperm fertility and early embryonic development in humans. Three groups of Chinese men were recruited： in vitro fertilization （IVF） group, including 374 couples who underwent conventional IVF; intracytoplasmic sperm injection （ICSI） group, including 294 couples who underwent an ICSI procedure using ejaculated sperm; and azoospermic group, consisting of 197 couples who underwent ICSI using either testis or epididymis sperm. Rsal polymorphism in the ERβ gene was detected by polymerase chain reaction （PCR）-restriction fragment length polymorphism technique; fertilization and high-quality embryo rates were evaluated for each group. In each group, no significant differences were found in the overall rates of fertilization and high-quality embryos among GG, AG and AA genotypes. However, the proportion of cycles possessing a satisfactory high-quality embryo rate with the AA genotype was significantly lower than that in the wild-type GG genotype from each group. These results demonstrated that sperm possessing the ERβ RsalA genotype may have reduced fertilization ability and decreased early embryonic developmental potential, which could directly or indirectly contribute to the low fertilization rate and early embryonic developmental arrest in some cases.展开更多
Infertility has become a serious disease since it affects 10%–15%of couples worldwide,and male infertility contributes to about 50%of the cases.Notably,a significant decrease occurs in the newborn population by 7.82 ...Infertility has become a serious disease since it affects 10%–15%of couples worldwide,and male infertility contributes to about 50%of the cases.Notably,a significant decrease occurs in the newborn population by 7.82 million in 2020 compared to 2016 in China.As such,it is essential to explore the effective methods of obtaining functional male gametes for restoring male fertility.Stem cells,including embryonic stem cells(ESCs),induced pluripotent stem cells(iPSCs),spermatogonial stem cells(SSCs),and mesenchymal stem cells(MSCs),possess the abilities of both self-renewal and differentiation into germ cells.Significantly,much progress has recently been achieved in the generation of male germ cells in vitro from various kinds of stem cells under the specified conditions,e.g.,the coculturing with Sertoli cells,three-dimensional culture system,the addition of growth factors and cytokines,and/or the overexpression of germ cell-related genes.In this review,we address the current advance in the derivation of male germ cells in vitro from stem cells based on the studies of the peers and us,and we highlight the perspectives and potential application of stem cell-derived male gametes in reproductive medicine.展开更多
Dear Editor,An interesting article from Zhao et al.recently published in Asian Journal of Andrology,has shown the association of a novel loss-of function(LOF)variant in PARN-like ribonuclease domain-containing exonucl...Dear Editor,An interesting article from Zhao et al.recently published in Asian Journal of Andrology,has shown the association of a novel loss-of function(LOF)variant in PARN-like ribonuclease domain-containing exonuclease 1(PNLDCI)and male infertility,and we would like to contribute a commentary on this article.展开更多
When we look back at-more than four decades-the history of assisted reproductive treatments(ART),a continuous effort to optimise laboratory conditions and to improve treatment protocols can be seen.In basic terms,the ...When we look back at-more than four decades-the history of assisted reproductive treatments(ART),a continuous effort to optimise laboratory conditions and to improve treatment protocols can be seen.In basic terms,the aim of research about culture media and laboratory environments is to create as more physiological condition as possible,which means reducing the gap between the not-fully-known in vivo conditions and their in vitro counterparts.展开更多
Yes-associated protein 1(YAP1)is a downstream effector of the Hippo signaling pathway,and it is involved in tumorigenesis,tissue repair,growth,and development.In this review,the biological roles and the mechanisms of ...Yes-associated protein 1(YAP1)is a downstream effector of the Hippo signaling pathway,and it is involved in tumorigenesis,tissue repair,growth,and development.In this review,the biological roles and the mechanisms of YAP1 in mediating stem cell fate decisions are discussed,including cell proliferation,differentiation,and apoptosis.In general,YAP1 promotes the proliferation and differentiation of stem cells,including embryonic stem cells and adult stem cells.It inhibits apoptosis by binding to the transcription factors,e.g.,transcriptional enhanced associate domain(TEAD),Smad,runt-related transcription factor 1/2,p73,p63,and Erb84,to maintain tissue homeostasis.The translocalization of YAP1 in cellular nuclei and the phosphorylation in the cytoplasm work as important and unusual events for the activation of YAP1.Moreover,YAP1 serves as the crosstalk for the Hippo pathway and other signaling pathways,including the Wnt and Notch pathways.It is highlighted in this review that YAP1 is an essential regulator for stem cells that have significant applications in regenerative medicine and reproductive medicine.展开更多
Objective:To study the effects of preconceptional thyroid-stimulating hormone(TSH)levels on antral follicle count(AFC)and pregnancy outcomes in a firstin vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI)...Objective:To study the effects of preconceptional thyroid-stimulating hormone(TSH)levels on antral follicle count(AFC)and pregnancy outcomes in a firstin vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI)cycle.Methods:A retrospective cohort study was conducted to explore the effects of preconceptional TSH levels on AFC and pregnancy outcomes in 1340 patients.The patients were divided into three groups:group 1,0.55≤TSH<2.5μIU/mL(n=868);group 2,2.5≤TSH<4.0μIU/mL(n=334);and group 3,TSH≥4.0μIU/mL(n=138).Results:There were significant differences in AFC(P=0.002),number of zygotes(P=0.008),and fertilization rate(P=0.015)among the three groups.Among the three groups,there were no obvious differences in live birth(P=0.559),high-quality embryo(P=0.108),or clinical pregnancy(P=0.939)rates.Binary logistics regression analysis showed that TSH correlated with AFC when TSH was≥4μIU/mL(P=0.033);however,TSH levels had no effect on live birth or clinical pregnancy rate.Conclusions:Although the preconceptional TSH level negatively related with AFC,number of zygotes,and fertility rate,especially when TSH was>4μIU/mL,TSH was not an independent factor on the live birth rate among fertile women undergoing their first IVF/ICSI-embryo transfer treatment.The effect of TSH levels on couples undergoing assisted reproductive technology requires further investigation.展开更多
The adverse effect of ambient PM_(2.5) exposure on very early pregnancy(VEP)remains controversial among epidemiological studies but is supported by toxicological evidence.We adopted a multicenter retrospective cohort ...The adverse effect of ambient PM_(2.5) exposure on very early pregnancy(VEP)remains controversial among epidemiological studies but is supported by toxicological evidence.We adopted a multicenter retrospective cohort of 141,040 cycles to evaluate the effect of PM_(2.5) exposure on the VEP using the in vitro fertilization and embryo transfer platform and high-resolution PM_(2.5) data in China.We first investigated the association between PM_(2.5) exposure 1 week before and 1 week after the embryo transfer date and VEP.The average PM_(2.5) concentrations of the 2 weeks were approximately 47μg/m^(3).The pooled results revealed a negative association between women’s accumulated PM_(2.5) exposure during the 2 weeks near the day of embryo transfer and success odds of VEP with the relative risk of 0.999(95%CI:0.997-0.999)at each increase of 10μg/m3.The women with the fresh cycle or one transplanted embryo were considered as a vulnerable population.Furthermore,seven periods for the fresh cycle and five periods for the frozen cycle from 85 days before oocyte retrieval to the day of gestational sac detection by ultrasound detection were defined.For these exposure periods,no association between the average PM_(2.5) exposure and VEP risk was identified.Our study provided large-scale population evidence for the association between PM_(2.5) exposure near embryo transfer day and VEP and identified vulnerable populations among women undergoing in vitro fertilization-embryo transfer.展开更多
Decidual natural killer （dNK） cells actively participate in the establishment and maintenance of maternal-fetal immune tolerance and act as local guardians against infection. However, how dNK cells maintain the immu...Decidual natural killer （dNK） cells actively participate in the establishment and maintenance of maternal-fetal immune tolerance and act as local guardians against infection. However, how dNK cells maintain the immune balance between tolerance and anti-infection immune responses during pregnancy remains unknown. Here, we demonstrated that the inhibitory molecule T-cell immunoglobulin domain and mucin domain-containing molecule-3 （Tim-3） are expressed on over 60% of dNK cells. Tim-3^＋ dNK cells display higher interleukin （IL）-4 and lower tumor necrosis factor （TNF）-α and perforin production. Human trophoblast cells can induce the transformation of peripheral NK cells into a dNK-like phenotype via the secretion of galectin-9 （Gal-9） and the interaction between Gal-9 and Tim-3. In addition, trophoblasts inhibit lipopolysaccharide （LPS）-induced pro-inflammatory cytokine and perforin production by dNK cells, which can be attenuated by Tim-3 neutralizing antibodies. Interestingly, a decreased percentage of Tim-3-expressing dNK cells were observed in human miscarriages and murine abortion-prone models. Moreover, T helper （Th）2-type cytokines were decreased and Thl-type cytokines were increased in Tim-3^＋ but not Tim-3- dNK cells from human and mouse miscarriages. Therefore, our results suggest that the Gal-9/Tim-3 signal is important for the regulation of dNK cell function, which is beneficial for the maintenance of a normal pregnancy.展开更多
Background It remains almost a helpless situation for the recurrent implantation failure and pregnancy loss caused by endometrial injury at present. The purpose of this study was to develop a rabbit model of endometri...Background It remains almost a helpless situation for the recurrent implantation failure and pregnancy loss caused by endometrial injury at present. The purpose of this study was to develop a rabbit model of endometrial mechanical injury that could provide a research platform for this difficult clinical predicament. Methods Three experiments were conducted. Experiment 1： Curettages in both uterus horns and copper wire inserting after curettage （double-injury） in one horn. The histological changes were monitored at 0, 24, 48, 72 hours, as well as in 1 and 2 weeks after operation. Experiment 2： Direct copper wire inserting in one horn and double-injury in other horn. The wires in both horns were removed after 2 weeks.展开更多
With the development of human assisted reproductive technology(ART),an objective,accurate,and non-invasive method to assess the quality and viability of oocytes and embryos remains one of the most significant goals.Gr...With the development of human assisted reproductive technology(ART),an objective,accurate,and non-invasive method to assess the quality and viability of oocytes and embryos remains one of the most significant goals.Granulosa cells(GCs)play an essential role in oocyte development.GCs can differentiate into mural GCs(MGCs)and cumulus cells(CCs)under the influence of oocytes.MGCs promote the growth and development of follicles by secreting cytokines and steroid hormones.Simultaneously,CCs can form cumulus-oocyte complexes to communicate with oocytes through gap junctions and promote oocyte growth and maturation.Seeking suitable biomarkers in GCs provides a direction for the non-invasive assessment of oocyte and embryo abilities during ART procedures.To date,only a few studies have investigated potentially effective GC biomarkers during ART processes,such as the apoptosis of GCs,transcriptomic characteristics of GCs,quality and quantity of mitochondria in GCs,and telomere length of such cells.These are potential reference indices for screening high-quality oocytes and embryos.Independent studies on MGCs and CCs can provide more effective results.Although there is scope for optimization and improvement,the results have become increasingly accurate with the constant advances in technology.Due to the heterogeneity of the study population and technical limitations,clinical tests for GCs cannot be performed as part of routine tests,but their prospects are promising.This article reviews the biomarkers that have been studied in MGCs and CCs.展开更多
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supported by the National Natural Science Foundation of China(No.82371515)the Talent Initiation BaiRen Plan Start-up Funds(No.E251F811)the State Key Laboratory of Integrated Management of Pest Insects and Rodents(No.IPM2301),China.
文摘Grooming,as an evolutionarily conserved repetitive behavior,is common in various animals,including humans,and serves essential functions including,but not limited to,hygiene maintenance,thermoregulation,de-arousal,stress reduction,and social behaviors.In rodents,grooming involves a patterned and sequenced structure,known as the syntactic chain with four phases that comprise repeated stereotyped movements happening in a cephalocaudal progression style,beginning from the nose to the face,to the head,and finally ending with body licking.The context-dependent occurrence of grooming behavior indicates its adaptive significance.This review briefly summarizes the neural substrates responsible for rodent grooming behavior and explores its relevance in rodent models of neuropsychiatric disorders and neurodegenerative diseases with aberrant grooming phenotypes.We further emphasize the utility of rodent grooming as a reliable measure of repetitive behavior in neuropsychiatric models,holding promise for translational psychiatry.Herein,we mainly focus on rodent self-grooming.Allogrooming(grooming being applied on one animal by its conspecifics via licking or carefully nibbling)and heterogrooming(a form of grooming behavior directing towards another animal,which occurs in other contexts,such as maternal,sexual,aggressive,or social behaviors)are not covered due to space constraints.
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.
文摘This study aimed to ascertain the current status of Japanese sperm banking for young cancer patients. During 2015, we mailed the directors of 695 institutes where sperm cryopreservation might be performed with questionnaires requesting information on the number of patients, age, precryopreservation chemotherapy, semen analyses results and diagnoses, cryopreservation success rate, and causes of unsuccessful cryopreservation. Of these 695 institutes, 92 had cryopreserved sperm before chemotherapy within the study period. In all, 820 cancer patients （237 testicular, 383 hematological, 46 bone and soft tissue, 20 brain, and 134 other malignancy） consulted the responding institutes for sperm cryopreservation. Except for testicular tumor, the number of patients whose sperm was preserved before cancer treatment was low compared to that of young cancer patients. Approximately 20% of patients with malignancies other than testicular tumor underwent chemotherapy before cryopreservation. The success rate of cryopreservation in hematological malignancy was 82.5%, significantly lower than that of both the testicular cancer （93.6%） and other malignancy groups （95.6%） （P 〈 0.05）. The primary reasons for preservation failure were azoospermia and poor semen quality. Patients with hematological malignancies had a higher rate of unsuccessful cryopreservation compared to those in other groups, possibly due to the large number of patients requesting sperm cryopreservation after chemotherapy induction. In Japan, information regarding sperm banking prior to cancer treatment appears to be lacking. Information regarding sperm preservation before chemotherapy should be provided to all Japanese oncologists.
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 Key Research&Development Program of the Ministry of Science and Technology of China[Grant No.2022YFE01349002023YFC3708305]+2 种基金the Strategy Priority Research Program(Category B)of Chinese Academy of Sciences[No.XDB0750300]the Yunnan Major Scientific and Technological Projects[Grant No.202202AG050019]the National Natural Science Foundation of China[Grant No.42077390].
文摘Objective To investigate the relationship and potential pathways between metal(loid)exposure and the risk of polycystic ovary syndrome(PCOS)in women of childbearing age.Methods This case-control study included 200 patients with PCOS(cases)and 896 non-PCOS controls with the age of 25-37 years.The concentrations of 29 metal(loid)s in the follicular fluid(FF)and clinical indicators in the serum were measured in all participants.Logistic regression analysis and mediation analysis were conducted to evaluate the associations between metal(loid)exposure and PCOS risk and investigate the possible roles of clinical indicators,respectively.Results Logistic regression analysis revealed an association between high copper levels in FF and increased PCOS risk(highest vs.lowest quartile:adjusted odds ratio=2.94,95%confidence interval:1.83-4.72).A high luteinizing hormone/follicle-stimulating hormone ratio and elevated levels of testosterone and anti-Müllerian hormone(AMH)were strongly associated with increased PCOS risk induced by high copper exposure.The mediation analysis indicated a mediating effect of AMH in the association between copper exposure and PCOS risk.Conclusion Copper may affect PCOS risk through the hypothalamic-pituitary-ovarian axis,mediated by AMH.Copper exposure and internal AMH levels are important indicators for early warning of PCOS development.
基金funded by the grants from National Nature Science Foundation of China(32470904 and 32170862)Major Scientific and Technological Projects for Collaborative Prevention and Control of Birth Defect in Hunan Province(2019SK1012)+3 种基金Key Grant of Research and Development in Hunan Province(2020DK2002)Developmental Biology and Breeding(2022XKQ0205)Shanghai Key Laboratory of Reproductive Medicine,Natural Science Foundation of Hunan Province of China(2024JJ5284,2023JJ30424,and 2024JJ5282)Research Foundation of Education Bureau of Hunan Province for Outstanding Young(23B0064).
文摘Spermatogenesis is a sophisticated biological process by which spermatogonial stem cells(SSCs)undergo self-renewal and differentiation into spermatozoa.Molecular mechanisms underlying fate determinations of human SSCs by key genes and signaling pathways remain elusive.Here,we report for the first time that Yes1-associated transcriptional regulator(YAP1)is required for fate determinations of SSCs and male fertility by interacting with RAD21 and targeting NEDD4 in humans and mice.YAP1 was mainly located at cell nuclei of human SSCs.YAP1 silencing resulted in the decreases in proliferation and DNA synthesis as well as an enhancement in apoptosis of human SSCs both in vivo and in vitro.RNA sequencing and real-time polymerase chain reaction assays identified NEDD4 as a target of YAP1,and NEDD4 knockdown inhibited the proliferation of human SSCs and increased their apoptosis.Furthermore,YAP1 interacted with RAD21 to regulate NEDD4 transcription in human SSCs.Importantly,YAP1 abnormalities were found to be associated with non-obstructive azoospermia(NOA)as manifested as lower expression level of YAP1 in testicular tissues of NOA patients and YAP1 single-nucleotide variants(SNVs)in 777 NOA patients.Finally,Yap1 germline conditional knockout(cKO)mice assumed mitotic arrest,low sperm count,and motility.Collectively,these results highlight a critical role of YAP1 in determining the fate determinations of human SSCs and male infertility through the YAP1/RAD21/NEDD4 pathway.This study provides new insights into the genetic regulatory mechanisms underlying human spermatogenesis and the pathogenesis of NOA,and it offers new targets for gene therapy of male infertility.
文摘Aim： To determine the possible roles of the t-complex testis expressed gene 5 （Tctex5） on sperm functions, the fulllength sequence of mRNA was studied and compared in the testis between the normal wild-type and the sterile t-haplotype mutant mice. Methods： We applied rapid amplification of cDNA ends, Northern blot and reverse transcription polymerase chain reaction to analyze the full length of Tctex5 mRNAs isolated from testes of the wild-type and the t-haplotype mice. Reverse transcription polymerase chain reaction was used to semi-quantitatively compare expression of Tctex5 transcripts in the 16 tissues and 9.5 day stage embryos in the wild-type mice. E-translation was applied to estimate the amino acid sequences. Results： One long and one short transcript of Tctex5 mRNA were discovered in mouse testis of wild-type （Tctex5^long-＋ and Tctex5^short-＋） and t-haplotype （Tctex5^long-＋ and Tctex5^short-＋） mice, respectively. Being enhanced only in the testis, Tctex5^long-＋ had 17 point mutations and one 15-bp-deletion in the exon 1 region, comparing with the Tctex5^long-＋, whereas the Tctex5^short-＋ was similar to the Tctex5^short-＋. The short isoforms of Tctex5 mRNAs in the two models encoded exactly the same peptides, but the long isoforms did not. The estimated peptide encoded by Tctex5^long-＋ had significant mutations on putative sites of phosphorylation and PP1 binding. Conclusion： We established that mutations that occur in the Tctex5 long transcript of the t-haplotype mice are important for normal sperm function, whereas the short transcript of Tctex5 might have a conserved function among different tissues. （Asian J Androl 2008 Mar; 10： 219-226）
文摘This paper aims to determine the possible role of estrogen receptor-β （ERβ） gene Rsal polymorphism on sperm fertility and early embryonic development in humans. Three groups of Chinese men were recruited： in vitro fertilization （IVF） group, including 374 couples who underwent conventional IVF; intracytoplasmic sperm injection （ICSI） group, including 294 couples who underwent an ICSI procedure using ejaculated sperm; and azoospermic group, consisting of 197 couples who underwent ICSI using either testis or epididymis sperm. Rsal polymorphism in the ERβ gene was detected by polymerase chain reaction （PCR）-restriction fragment length polymorphism technique; fertilization and high-quality embryo rates were evaluated for each group. In each group, no significant differences were found in the overall rates of fertilization and high-quality embryos among GG, AG and AA genotypes. However, the proportion of cycles possessing a satisfactory high-quality embryo rate with the AA genotype was significantly lower than that in the wild-type GG genotype from each group. These results demonstrated that sperm possessing the ERβ RsalA genotype may have reduced fertilization ability and decreased early embryonic developmental potential, which could directly or indirectly contribute to the low fertilization rate and early embryonic developmental arrest in some cases.
基金supported by the grants from the National Nature Science Foundation of China (32170862 and 31872845)Major Scientific and Technological Projects for Collaborative Prevention and Control of Birth Defect in Hunan Province (2019SK1012)+2 种基金Key Grant of Research and Development in Hunan Province (2020DK2002)High-Level Talent Gathering Project in Hunan Province (2018RS3066)Natural Science Foundation of Hunan Province of China (2020J5380 and 2020JJ5383).
文摘Infertility has become a serious disease since it affects 10%–15%of couples worldwide,and male infertility contributes to about 50%of the cases.Notably,a significant decrease occurs in the newborn population by 7.82 million in 2020 compared to 2016 in China.As such,it is essential to explore the effective methods of obtaining functional male gametes for restoring male fertility.Stem cells,including embryonic stem cells(ESCs),induced pluripotent stem cells(iPSCs),spermatogonial stem cells(SSCs),and mesenchymal stem cells(MSCs),possess the abilities of both self-renewal and differentiation into germ cells.Significantly,much progress has recently been achieved in the generation of male germ cells in vitro from various kinds of stem cells under the specified conditions,e.g.,the coculturing with Sertoli cells,three-dimensional culture system,the addition of growth factors and cytokines,and/or the overexpression of germ cell-related genes.In this review,we address the current advance in the derivation of male germ cells in vitro from stem cells based on the studies of the peers and us,and we highlight the perspectives and potential application of stem cell-derived male gametes in reproductive medicine.
基金This work was funded by the grant from the National Natural Science Foundation of China(No.32170862).
文摘Dear Editor,An interesting article from Zhao et al.recently published in Asian Journal of Andrology,has shown the association of a novel loss-of function(LOF)variant in PARN-like ribonuclease domain-containing exonuclease 1(PNLDCI)and male infertility,and we would like to contribute a commentary on this article.
文摘When we look back at-more than four decades-the history of assisted reproductive treatments(ART),a continuous effort to optimise laboratory conditions and to improve treatment protocols can be seen.In basic terms,the aim of research about culture media and laboratory environments is to create as more physiological condition as possible,which means reducing the gap between the not-fully-known in vivo conditions and their in vitro counterparts.
基金This work was supported by grants from the National Nature Science Foundation of China(32170862,31872845)Major Scientific and Technological Projects for Collaborative Prevention and Control of Birth Defect in Hunan Province(2019SK1012)+4 种基金Key Grant of Research and Development in Hunan Province(2020DK2002)High-Level Talent Gathering Project in Hunan Province(2018RS3066)Natural Science Foundation of Hunan Province(2020JJ5383,2021JJ40365)Health Commission Foundation of Hunan Province(202104052273,202102050927)Hunan Province College Student Research Learning and Innovative Experiment Project(S202010542084).
文摘Yes-associated protein 1(YAP1)is a downstream effector of the Hippo signaling pathway,and it is involved in tumorigenesis,tissue repair,growth,and development.In this review,the biological roles and the mechanisms of YAP1 in mediating stem cell fate decisions are discussed,including cell proliferation,differentiation,and apoptosis.In general,YAP1 promotes the proliferation and differentiation of stem cells,including embryonic stem cells and adult stem cells.It inhibits apoptosis by binding to the transcription factors,e.g.,transcriptional enhanced associate domain(TEAD),Smad,runt-related transcription factor 1/2,p73,p63,and Erb84,to maintain tissue homeostasis.The translocalization of YAP1 in cellular nuclei and the phosphorylation in the cytoplasm work as important and unusual events for the activation of YAP1.Moreover,YAP1 serves as the crosstalk for the Hippo pathway and other signaling pathways,including the Wnt and Notch pathways.It is highlighted in this review that YAP1 is an essential regulator for stem cells that have significant applications in regenerative medicine and reproductive medicine.
基金Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support(YGLX202311)Clinical Incubation Project of Beijing Chao-Yang Hospital(CYFH202307)。
文摘Objective:To study the effects of preconceptional thyroid-stimulating hormone(TSH)levels on antral follicle count(AFC)and pregnancy outcomes in a firstin vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI)cycle.Methods:A retrospective cohort study was conducted to explore the effects of preconceptional TSH levels on AFC and pregnancy outcomes in 1340 patients.The patients were divided into three groups:group 1,0.55≤TSH<2.5μIU/mL(n=868);group 2,2.5≤TSH<4.0μIU/mL(n=334);and group 3,TSH≥4.0μIU/mL(n=138).Results:There were significant differences in AFC(P=0.002),number of zygotes(P=0.008),and fertilization rate(P=0.015)among the three groups.Among the three groups,there were no obvious differences in live birth(P=0.559),high-quality embryo(P=0.108),or clinical pregnancy(P=0.939)rates.Binary logistics regression analysis showed that TSH correlated with AFC when TSH was≥4μIU/mL(P=0.033);however,TSH levels had no effect on live birth or clinical pregnancy rate.Conclusions:Although the preconceptional TSH level negatively related with AFC,number of zygotes,and fertility rate,especially when TSH was>4μIU/mL,TSH was not an independent factor on the live birth rate among fertile women undergoing their first IVF/ICSI-embryo transfer treatment.The effect of TSH levels on couples undergoing assisted reproductive technology requires further investigation.
基金National Key Research&Development Program of Ministry of Science and Technology of China,No.2023YFC3708305(ZPB),2022YFE0134900(JL),and 2022YFC2704404(QL)National Natural Science Foundation of China,No.42077390(BW),41771527(BW)Yunnan Major Scientific and Technological Projects,No.202202AG050019(BP).
文摘The adverse effect of ambient PM_(2.5) exposure on very early pregnancy(VEP)remains controversial among epidemiological studies but is supported by toxicological evidence.We adopted a multicenter retrospective cohort of 141,040 cycles to evaluate the effect of PM_(2.5) exposure on the VEP using the in vitro fertilization and embryo transfer platform and high-resolution PM_(2.5) data in China.We first investigated the association between PM_(2.5) exposure 1 week before and 1 week after the embryo transfer date and VEP.The average PM_(2.5) concentrations of the 2 weeks were approximately 47μg/m^(3).The pooled results revealed a negative association between women’s accumulated PM_(2.5) exposure during the 2 weeks near the day of embryo transfer and success odds of VEP with the relative risk of 0.999(95%CI:0.997-0.999)at each increase of 10μg/m3.The women with the fresh cycle or one transplanted embryo were considered as a vulnerable population.Furthermore,seven periods for the fresh cycle and five periods for the frozen cycle from 85 days before oocyte retrieval to the day of gestational sac detection by ultrasound detection were defined.For these exposure periods,no association between the average PM_(2.5) exposure and VEP risk was identified.Our study provided large-scale population evidence for the association between PM_(2.5) exposure near embryo transfer day and VEP and identified vulnerable populations among women undergoing in vitro fertilization-embryo transfer.
文摘Decidual natural killer （dNK） cells actively participate in the establishment and maintenance of maternal-fetal immune tolerance and act as local guardians against infection. However, how dNK cells maintain the immune balance between tolerance and anti-infection immune responses during pregnancy remains unknown. Here, we demonstrated that the inhibitory molecule T-cell immunoglobulin domain and mucin domain-containing molecule-3 （Tim-3） are expressed on over 60% of dNK cells. Tim-3^＋ dNK cells display higher interleukin （IL）-4 and lower tumor necrosis factor （TNF）-α and perforin production. Human trophoblast cells can induce the transformation of peripheral NK cells into a dNK-like phenotype via the secretion of galectin-9 （Gal-9） and the interaction between Gal-9 and Tim-3. In addition, trophoblasts inhibit lipopolysaccharide （LPS）-induced pro-inflammatory cytokine and perforin production by dNK cells, which can be attenuated by Tim-3 neutralizing antibodies. Interestingly, a decreased percentage of Tim-3-expressing dNK cells were observed in human miscarriages and murine abortion-prone models. Moreover, T helper （Th）2-type cytokines were decreased and Thl-type cytokines were increased in Tim-3^＋ but not Tim-3- dNK cells from human and mouse miscarriages. Therefore, our results suggest that the Gal-9/Tim-3 signal is important for the regulation of dNK cell function, which is beneficial for the maintenance of a normal pregnancy.
文摘Background It remains almost a helpless situation for the recurrent implantation failure and pregnancy loss caused by endometrial injury at present. The purpose of this study was to develop a rabbit model of endometrial mechanical injury that could provide a research platform for this difficult clinical predicament. Methods Three experiments were conducted. Experiment 1： Curettages in both uterus horns and copper wire inserting after curettage （double-injury） in one horn. The histological changes were monitored at 0, 24, 48, 72 hours, as well as in 1 and 2 weeks after operation. Experiment 2： Direct copper wire inserting in one horn and double-injury in other horn. The wires in both horns were removed after 2 weeks.
基金Beijing Natural Science Foundation(7202052)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(XMLX201825)+1 种基金National Natural Science Foundation of China(81471511)New Star Personnel Training Plan of Chao-Yang Hospital(to WHZ CYXX-2017-19)。
文摘With the development of human assisted reproductive technology(ART),an objective,accurate,and non-invasive method to assess the quality and viability of oocytes and embryos remains one of the most significant goals.Granulosa cells(GCs)play an essential role in oocyte development.GCs can differentiate into mural GCs(MGCs)and cumulus cells(CCs)under the influence of oocytes.MGCs promote the growth and development of follicles by secreting cytokines and steroid hormones.Simultaneously,CCs can form cumulus-oocyte complexes to communicate with oocytes through gap junctions and promote oocyte growth and maturation.Seeking suitable biomarkers in GCs provides a direction for the non-invasive assessment of oocyte and embryo abilities during ART procedures.To date,only a few studies have investigated potentially effective GC biomarkers during ART processes,such as the apoptosis of GCs,transcriptomic characteristics of GCs,quality and quantity of mitochondria in GCs,and telomere length of such cells.These are potential reference indices for screening high-quality oocytes and embryos.Independent studies on MGCs and CCs can provide more effective results.Although there is scope for optimization and improvement,the results have become increasingly accurate with the constant advances in technology.Due to the heterogeneity of the study population and technical limitations,clinical tests for GCs cannot be performed as part of routine tests,but their prospects are promising.This article reviews the biomarkers that have been studied in MGCs and CCs.
