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 (n = 5), and from GV (n = 8) and metaphase II (MII) oocytes (n = 12) after 48 h of In Vitro maturation (IVM). Microarray analysis revealed active signaling pathways during IVM, emphasizing LHCGR 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.
{"title":"Transcriptional Changes in Cumulus Cells During In Vitro Maturation of Human Oocytes","authors":"Jesús Cadenas, Cristina Subiran Adrados, Stine Gry Kristensen, Kirsten Tryde Macklon, Vinnie Hornshøj Greve, Jens Fedder, Linn Salto Mamsen, 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}
Kaupp, U. B. and O. Kendall. 2024. “David Garbers' Contributions to Chemotaxis Signaling in Sperm.” Molecular Reproduction and Development 91: e23774. https://doi.org/10.1002/mrd.23774
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.
We apologize for this error.
卡普,U. B.和O.肯德尔,2024。“ David Garbers对精子趋化性信号的贡献”生殖与发育学报(自然科学版)[j];https://doi.org/10.1002/mrd.23774The作者指出,他们注意到,正如文章中所述,HC Lee博士没有加入David Garber的实验室。相反,当时在明尼苏达大学(University of Minnesota)的李博士与加伯斯博士合作研究Na/H交换的性质。我们为这个错误道歉。
{"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}
Qi-En Yang, Mingyao Yang, Melissa J. Oatley, Jon M. Oatley
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 Id4 in prospermatogonia led to a block in meiotic progression of spermatocytes during postnatal spermatogenesis. In contrast, meiotic progression was found to proceed when Id4 was conditionally overexpressed beginning in postnatal spermatogonia. Moreover, conditional overexpression of Id4 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.
{"title":"Programming for Meiotic Competence in Mouse Male Germ Cells is Established at the Perinatal Precursor Stage of Development","authors":"Qi-En Yang, Mingyao Yang, Melissa J. Oatley, 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}
Ana Clara da Costa Nunes Gomes, Laura Eduarda S. C. Pagliari, Taiza Stumpp, Vanessa Vendramini
Epigenetic changes caused by methylphenidate hydrochloride on paternal inheritance have been suggested in fish, yet a subject to be determined in mammals. In rats, we showed increased sperm DNA fragmentation and reduced embryonic viability. In the present report, male Wistar rats (n = 21) were divided into two groups: control and methylphenidate. The control group received 1 mL/kg of distilled water, while the methylphenidate group received 5 mg/kg by gavage from 38 to 68 days of age on a single daily dose. After this period, there was an interval before exposed rats started a mating schedule with untreated/normally cycling females. Morphological quality and key epigenetic marks in the blastocysts were assessed. Immunocytochemistry was performed in fresh blastocysts to quantify the trimethylated histones H3K4, H3K9, and H4K20. Treatment with methylphenidate reduced the mean quality of blastocysts by 43.57% (p = 0.02), as well as increased those classified as “poor” by more than 150% (p < 0.001). Epigenetic marks were also altered, with an increase in the intensity of H3K9me3 (p = 0.01), a reduction of H4K20me3 (p = 0.05) and a nonsignificant increase of H3K4me3 (p = 0.34). The results suggest that the decline in blastocyst quality is highly associated with subchronic use of this psychostimulant by adolescent males. This is the first report showing the risks posed by methylphenidate to the epigenetic signature of a mammalian blastocyst following paternal exposure.
{"title":"Paternal Exposure to Methylphenidate Induces Poor-Quality Blastocyst and Epigenetic Changes","authors":"Ana Clara da Costa Nunes Gomes, Laura Eduarda S. C. Pagliari, Taiza Stumpp, Vanessa Vendramini","doi":"10.1002/mrd.70026","DOIUrl":"https://doi.org/10.1002/mrd.70026","url":null,"abstract":"<p>Epigenetic changes caused by methylphenidate hydrochloride on paternal inheritance have been suggested in fish, yet a subject to be determined in mammals. In rats, we showed increased sperm DNA fragmentation and reduced embryonic viability. In the present report, male <i>Wistar</i> rats (<i>n</i> = 21) were divided into two groups: control and methylphenidate. The control group received 1 mL/kg of distilled water, while the methylphenidate group received 5 mg/kg by gavage from 38 to 68 days of age on a single daily dose. After this period, there was an interval before exposed rats started a mating schedule with untreated/normally cycling females. Morphological quality and key epigenetic marks in the blastocysts were assessed. Immunocytochemistry was performed in fresh blastocysts to quantify the trimethylated histones H3K4, H3K9, and H4K20. Treatment with methylphenidate reduced the mean quality of blastocysts by 43.57% (<i>p</i> = 0.02), as well as increased those classified as “poor” by more than 150% (<i>p</i> < 0.001). Epigenetic marks were also altered, with an increase in the intensity of H3K9me3 (<i>p</i> = 0.01), a reduction of H4K20me3 (<i>p</i> = 0.05) and a nonsignificant increase of H3K4me3 (<i>p</i> = 0.34). The results suggest that the decline in blastocyst quality is highly associated with subchronic use of this psychostimulant by adolescent males. This is the first report showing the risks posed by methylphenidate to the epigenetic signature of a mammalian blastocyst following paternal exposure.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.70026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118147","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}