Molecular Reproduction and Development最新文献

{"title":"Regulatory Role of Tubulin Beta 1 in Oocyte Endoplasmic Reticulum Stress and Mitochondrial Integrity via Transforming Growth Factor-β1 Signaling Pathway in Mice","authors":"Yan Li,&nbsp;Yan Dong,&nbsp;Xiaoxia Lin,&nbsp;Xueyuan Zhou,&nbsp;Li Ma,&nbsp;Hua Jin","doi":"10.1002/mrd.70042","DOIUrl":"https://doi.org/10.1002/mrd.70042","url":null,"abstract":"<div>\u0000 \u0000 <p>Enhancing the developmental competence and quality of oocytes cultured in vitro remains challenging, in part due to limited understanding of the structural and molecular regulators of oocyte maturation. Microtubules, as key components of the cytoskeleton, are essential for chromosome segregation and meiotic progression. Tubulin beta 1 class VI (TUBB1) plays crucial roles in cellular stability, yet its involvement in regulating endoplasmic reticulum (ER) stress and mitochondrial function in oocytes via immune checkpoint pathways remains unclear. This study aimed to investigate the role of TUBB1 in regulating ER stress and mitochondrial integrity in oocytes via the transforming growth factor-β1 (TGF-β1)/SMAD family member 3 (Smad3) pathway, and its potential implications for improving assisted reproductive technologies. First, oocytes isolated from ICR female mice were subjected to oxidative stress using hydrogen peroxide (H₂O₂) to investigate TUBB1 expression. Next, lentiviral vectors and a TGF-β1/Smad3 activator (SRI-011381 hydrochloride) were utilized to modulate pathway activity. ER stress, mitochondrial integrity, oxidative stress, and apoptosis were subsequently assessed. H₂O₂ exposure significantly reduced TUBB1 expression, confirming its susceptibility to oxidative stress. TUBB1 silencing exacerbated ER stress (elevated Bax, GRP78, Caspase-12; decreased Bcl-2), increased apoptosis rates, and caused mitochondrial dysfunction evidenced by disrupted mitochondrial morphology; increased Ca²⁺ levels, higher ROS and MDA, and lower SOD activity. Conversely, TUBB1 overexpression or direct activation of the TGF-β1/Smad3 pathway reversed these detrimental effects, significantly reducing apoptosis, normalizing mitochondrial distribution, and alleviating ER and oxidative stress. Furthermore, activation of the TGF-β1/Smad3 pathway in TUBB1-silenced oocytes (rescue group) effectively restored mitochondrial and ER stress parameters to normal levels. Our findings demonstrate that TUBB1 plays a critical role in modulating ER and mitochondrial stress responses in oocytes via the TGF-β1/Smad3 signaling pathway. Targeted regulation of TUBB1 may serve as a promising therapeutic approach to improve oocyte quality in assisted reproductive technologies.</p>\u0000 </div>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 7","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GABAA and GABAB Receptor Agonists Promote the Hypothalamic–Pituitary–Ovarian Axis in the Postfertilization Model Poecilia sphenops","authors":"Achyutham Hotha,&nbsp;C. B. Ganesh","doi":"10.1002/mrd.70041","DOIUrl":"https://doi.org/10.1002/mrd.70041","url":null,"abstract":"<div>\u0000 \u0000 <p>Although gamma-aminobutyric acid (GABA) is known to play a role in the regulation of several physiological functions in vertebrates, the role of GABA in regulating the reproductive axis in viviparous teleosts remains opaque. This study examined the effects of GABA_A and GABA_B receptor agonists, muscimol (MUSC) and baclofen (BAC), on the hypothalamic–pituitary–ovarian (HPO) axis in the black molly <i>Poecilia sphenops</i>. A dose-dependent upregulation of gonadotropin-releasing hormone-I (GnRH-I) mRNA expression in the preoptic hypothalamus was observed in 0.5 and 5 µg MUSC-treated fish compared to experimental controls; however, a significant upregulation of luteinizing hormone-β (LH-β) mRNA expression was observed only at the highest dose. A similar stimulatory effect on GnRH-I mRNA expression was observed in the 5, 10, or 50 µg BAC-treated group compared to experimental controls, but no significant change was observed in LH-β mRNA level. Furthermore, treatment with 0.5 or 5 µg MUSC stimulated the development of all stages of follicles in the ovary except for Stages IV or III, respectively. On the other hand, treatment with 50 µg BAC caused a significant increase in the numbers of Stages I–V follicles. These results were concomitant with a significant increase in some of the embryonic developmental stages and fecundity levels in 0.5 or 5 µg MUSC-treated or 50 µg BAC-treated fish compared to those of experimental controls. Together, these findings suggest that GABA_A and GABA_B receptor agonists produce a stimulatory effect on the HPO axis in a receptor-specific and concentration-dependent manner for the first time in a viviparous teleost.</p>\u0000 </div>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 7","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Administration of Exogenous Kisspeptin Induces Breeding Competence in Post-pubertal Female Common Carp (Cyprinus carpio)","authors":"Nehareeka Dan,&nbsp;Harsh Shah,&nbsp;A. V. Ramachandran,&nbsp;Parth Pandya","doi":"10.1002/mrd.70037","DOIUrl":"https://doi.org/10.1002/mrd.70037","url":null,"abstract":"<div>\u0000 \u0000 <p>Puberty is a crucial stage in vertebrates, controlled by complex neuroendocrine mechanisms, yet its precise pathways remain unclear. Kisspeptin and melatonin are central to this regulation, acting as opposing forces: kisspeptin activates the hypothalamic-pituitary-gonadal (HPG) axis, while melatonin suppresses it. Serotonin also influences GnRH secretion. Despite advancements, identifying novel hormonal agents is crucial for enhancing reproductive outcomes in artificial propagation. Therefore, this study aimed to investigate the effects of kisspeptin administration on the pubertal onset and reproductive efficiency in female Common carp (<i>Cyprinus carpio</i>), alongside its interaction with melatonin and serotonin in modulating the neuroendocrine reproductive axis. Common carp (6 ± 1.5 cm, 5.5 ± 2 g, and 5–6 months old) were divided into control, low-dose kisspeptin (100 ng/g), and high-dose kisspeptin (250 ng/g) groups. Fish received biweekly intramuscular kisspeptin injections for 4 weeks. Post-treatment, the brain and gonads were analyzed for hormonal assays, gene and protein expression analysis, and histology. Kisspeptin significantly increased gonadotropins, sex hormone, and serotonin while reducing melatonin levels. Key HPG axis genes (<i>kiss1</i>, <i>kiss2</i>, <i>kiss1r</i>, <i>gnrh2</i>, <i>gnrh3</i>, <i>gth1r</i>, <i>gth2r</i>, <i>esr1</i>) and serotonin receptor (<i>htr1ab</i>) were upregulated, whereas melatonin receptor (<i>mtnr1a</i>) and <i>gnih</i> were downregulated. Protein expression mirrored these results, showing increased levels of Kiss1, Kiss1R, 5-Ht2A, Gnrh2, and Esr1, with reduced Mtnr1A. Histological analysis revealed enhanced gonadal development, with more advanced oocytes in the higher-dose group. These findings demonstrate that kisspeptin accelerates puberty and enhances reproductive development in Common carp, offering significant potential for optimizing aquaculture breeding practices.</p>\u0000 </div>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A New Translation and Reader's Guide to the First Manuscript Published by Adolph von La Valette-St. George on Vertebrate Spermatogenesis","authors":"Susanne L. Jones,&nbsp;Delaney Meginniss,&nbsp;Christopher B. Geyer","doi":"10.1002/mrd.70005","DOIUrl":"https://doi.org/10.1002/mrd.70005","url":null,"abstract":"<p>This manuscript was originally written in German by one of the founding members of the field of spermatogenesis, Dr. Adolph von La Valette-St. George. Published in 1865, this important work carefully described, using samples from a wide variety of vertebrate species, essential aspects of male germ cells including the acrosome, the residual body of shed excess spermatid cytoplasm, and the flagellum. In addition, he correctly deduced that sperm formed from precursor germ cells rather than somatic cells and that their motility was due to movement of the flagellum. Here, we present an English translation and modern interpretation of one of Dr. La Valette-St. George's most important contributions from his lengthy productive academic career.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Bioactive Ingredient Quercetin in Guilu-Erxian-Glue Ameliorates Oligoasthenospermia in Mice via PKA/CREB Pathway-Dependent Sirt1 Activation and p53 Deacetylation","authors":"Yingqiu Li,&nbsp;Xianyu Tian,&nbsp;Minglian Wang,&nbsp;Chenxi Tang,&nbsp;Xinyu Du,&nbsp;Ling Dai,&nbsp;Zhanglei Ding,&nbsp;Qinkun Zhao,&nbsp;Qinghu He,&nbsp;Wen Sheng","doi":"10.1002/mrd.70036","DOIUrl":"https://doi.org/10.1002/mrd.70036","url":null,"abstract":"<div>\u0000 \u0000 <p>Oligoasthenospermia (OAS), a major cause of male infertility, was alleviated by Guilu-Erxian-Glue (GLEXG) in <i>Tripterygium wilfordii polyglycoside</i> (TWG)-induced rat models. This study identified GLEXG's bioactive ingredients and explored its therapeutic mechanism. Using network pharmacology and liquid chromatography-mass spectrometry, quercetin was predicted and validated as a key component of GLEXG. In vivo and in vitro, OAS models were established using TWG in mice and H₂O₂ in spermatocytes. TWG administration reduced testicle and epididymis indices, sperm concentration, vitality, and serum testosterone, luteinizing hormone, and follicle-stimulating hormone. It also increased germ cell apoptosis, upregulated Bax, cleaved caspase-3, and cleaved caspase-9, downregualted Bcl-2, PHB1, VDHC, SDHA, and CoxIV, and impaired mitochondrial function (reduced mitochondrial DNA copy number and membrane potential). Quercetin counteracted these effects in vivo and in vitro. Mechanistically, quercetin increased p-PKA/PKA and p-CREB/CREB ratios, upregulated Sirt1, and decreased Ac-p53/p53 ratio. These beneficial effects were abolished upon Sirt1 inhibition. Thus, quercetin in GLEXG ameliorated OAS by attenuating apoptosis and mitochondrial dysfunction via PKA/CREB pathway-dependent activation of Sirt1 and deacetylation of p53.</p></div>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Sexually Dimorphic Circulating MicroRNAs in Gonochoristic and Hermaphroditic Marine Fish Species","authors":"Benjamin Geffroy,&nbsp;Camille Houdelet,&nbsp;Eva Blondeau-Bidet,&nbsp;Xavier Mialhe,&nbsp;Aline Bajek,&nbsp;Jean-Claude Falguière,&nbsp;Yann Guiguen,&nbsp;Julien Bobe","doi":"10.1002/mrd.70038","DOIUrl":"https://doi.org/10.1002/mrd.70038","url":null,"abstract":"<div>\u0000 \u0000 <p>In many fish species, males and females are difficult to distinguish at the juvenile stage and size differences appear during maturation, often favoring females. Molecular tools for sexing live fish would benefit aquaculture, fisheries, and conservation research. Here we aimed to explore to what extent circulating microRNAs (miRNAs) can decipher phenotypic males from phenotypic females in gonochoristic fish species (the European seabass <i>Dicentrarchus labrax</i>, the Turbot <i>Scophthalmus maximus</i>, the Red drum <i>Sciaenops ocellatus</i>, and the Blue Runner <i>Caranx crysos</i>) as well as sexual stages in a protandrous hermaphrodite species (the Gilthead seabream <i>Sparus aurata</i>). We collected and extracted total RNA from 258 blood plasma samples, of which 96 samples with satisfactory RNA quality were sequenced using small RNA-seq. Circulating miRNAs detected in the plasma allowed to easily discriminate species, but some miRNAs were significantly correlated to one sex, independently of the species. In immature fishes, 3 miRNAs (miR-21a-3p, miR-18a-3p, and miR-29-1a-5p) were overexpressed in females compared to males, while in mature fish, miR-21a-3p exhibited an opposite pattern. In the Gilthead seabream, we detected that both miR-21a-3p and miR-125b-2/3-5p were possibly involved in the sexual transition from male to female. A complementary analysis on the 3′ UTR sequences of all fish species allowed to predict potential mRNA targets of those two miRNAs, some of them being particularly relevant regarding sexual development (i.e., wnt4, esrrb, esrrga and hsd17b1). The identification of miRNAs like miR-21a-3p and miR-125b-2/3-5p as potential sex markers could offer a new, poorly-invasive method to monitor sex and developmental stages in fishes.</p>\u0000 </div>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"c-Abl Plays an Important Role in Mouse Preimplantation Embryo Development and the Dysregulation Associated With Decreased mTERT Expression","authors":"Ecem Yildirim,&nbsp;Tugce Onel,&nbsp;Aylin Yaba","doi":"10.1002/mrd.70039","DOIUrl":"https://doi.org/10.1002/mrd.70039","url":null,"abstract":"<p>c-Abl encodes a cytoplasmic and nuclear protein tyrosine kinase that has been implicated in processes of cell growth, proliferation, differentiation, division, and regulation of cytoskeletal structure. mTERT is a catalytic subunit of mouse telomerase and it is very important for controlling cell proliferation and homeostasis by maintaining telomere length. We demonstrated before the interaction between c-Abl and mTERT in mouse ovary and we suggested a role for c-Abl in the regulation of telomerase function and proliferation in mouse granulosa cells. The current study aims to examine the c-Abl and mTERT expression and potential interactions through mouse preimplantation embryonic development. To assess c-Abl's function in embryonic development, siRNA-mediated silencing of the <i>c-Abl</i> was used in mouse preimplantation embryos. After siRNA transfection, the immunofluorescence was used to examine the c-Abl pattern at embryonic development. Next, the levels of <i>mTERT</i> and <i>c-Abl</i> mRNA were compared. The results show that c-Abl is expressed in mouse preimplantation embryos at all developmental stages, with the cytoplasmic expression all through from the 2-cell to the blastocyst. Additionally, c-Abl is presented very intense expression in blastomer-blastomer junctions. The siRNA-mediated depletion of <i>c-Abl</i> showed developmental abnormalities at the 8- to 16-cell and morula to blastocyst and also with significantly decreased blastocyst development rate. Moreover, expression of the mTERT telomerase catalytic subunit was significantly reduced in <i>c-Abl</i>-depleted embryos during preimplantation embryonic development. Finally, we demonstrate that c-Abl may play a crucial role in compaction and preimplantation embryo development, and that the relationship between c-Abl and mTERT has developmental importance in early embryogenesis.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional Changes in Cumulus Cells During In Vitro Maturation of Human Oocytes","authors":"Jesús Cadenas,&nbsp;Cristina Subiran Adrados,&nbsp;Stine Gry Kristensen,&nbsp;Kirsten Tryde Macklon,&nbsp;Vinnie Hornshøj Greve,&nbsp;Jens Fedder,&nbsp;Linn Salto Mamsen,&nbsp;Claus Yding Andersen","doi":"10.1002/mrd.70035","DOIUrl":"https://doi.org/10.1002/mrd.70035","url":null,"abstract":"<p>This study assessed transcriptional changes in human cumulus cells (CCs) during oocyte maturation In Vitro. CCs were collected from 25 cumulus-oocyte complexes derived from surplus ovarian medulla tissue of eight women (mean age 29 years, range 19–36) undergoing ovarian tissue cryopreservation without ovarian stimulation. Samples included CCs from fresh germinal vesicle (GV) oocytes (<i>n</i> = 5), and from GV (<i>n</i> = 8) and metaphase II (MII) oocytes (<i>n</i> = 12) after 48 h of In Vitro maturation (IVM). Microarray analysis revealed active signaling pathways during IVM, emphasizing <i>LHCGR</i> upregulation as central to oocyte maturation. Enhanced pathways included the insulin-like growth factor (IGF) system, particularly IGF2, and activin/inhibin signaling, while others appeared less active In Vitro compared to In Vivo. Differential expression analysis identified 1763 significantly expressed genes (DEGs) between fresh GV and MII-IVM, 50 DEGs between GV-IVM and MII-IVM, and 339 novel or unknown transcripts. Clustering highlighted additional pathways, such as MAPK, PPAR, Wnt, cholesterol metabolism, PI3K-AKT, TGF-β, focal adhesion, actin cytoskeleton regulation, and RANK/RANKL, with differential regulation during IVM. These findings underscore the complexity of signaling in CCs and the distinct regulatory mechanisms of human oocyte maturation In Vitro compared to In Vivo.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “David Garbers' Contributions to Chemotaxis Signaling in Sperm”","authors":"","doi":"10.1002/mrd.70033","DOIUrl":"https://doi.org/10.1002/mrd.70033","url":null,"abstract":"<p>Kaupp, U. B. and O. Kendall. 2024. “David Garbers' Contributions to Chemotaxis Signaling in Sperm.” <i>Molecular Reproduction and Development</i> 91: e23774. https://doi.org/10.1002/mrd.23774</p><p>The authors note that it came to their attention that Dr. HC Lee did not join David Garber's laboratory, as stated in the article. Instead, Dr. Lee, then at the University of Minnesota, collaborated with Dr. Garbers on the properties of Na/H exchange.</p><p>We apologize for this error.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Programming for Meiotic Competence in Mouse Male Germ Cells is Established at the Perinatal Precursor Stage of Development","authors":"Qi-En Yang,&nbsp;Mingyao Yang,&nbsp;Melissa J. Oatley,&nbsp;Jon M. Oatley","doi":"10.1002/mrd.70032","DOIUrl":"https://doi.org/10.1002/mrd.70032","url":null,"abstract":"<p>Meiosis is a fundamental aspect of gametogenesis, but how and when the programming is established in germ cells during development is unknown. In the mammalian male germline, mitotic differentiating spermatogonia with the competence for meiotic divisions arise from an undifferentiated pool of spermatogonia that are descended from prospermatogonial precursors. Here we provide evidence from mouse models that suggests programming for meiotic competence is established much earlier in the developmental trajectory of spermatogonia than previously believed, likely at the prospermatogonial stage in fetal life. Conditional overexpression of the gene <i>Id4</i> in prospermatogonia led to a block in meiotic progression of spermatocytes during postnatal spermatogenesis. In contrast, meiotic progression was found to proceed when <i>Id4</i> was conditionally overexpressed beginning in postnatal spermatogonia. Moreover, conditional overexpression of <i>Id4</i> in the female germline beginning at the fetal stage of development after oocytes have initiated meiosis did not disrupt their ability to progress postnatally. Collectively, these findings suggest that a new stage for where mechanistic insights into the origin of meiotic competence in the male germline should be explored. Moreover, the findings place further precedence on defining how outside exposures can disrupt programming at the earliest stages of male germ cell development that will manifest at advanced maturation stages and lead to genomic abnormalities.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}