Biology of Reproduction最新文献_第8页

The crazy ovary 2: a tribute to Ken McNatty. 疯狂的卵巢2：致敬肯·麦克纳蒂†。

IF 3 2区生物学

Biology of Reproduction Pub Date : 2026-03-16 DOI: 10.1093/biolre/ioaf282

Philippe Monget, Rozenn Dalbies-Tran, Jean-Jacques Lareyre, Gabriel Livéra, Feriel Yasmine Mahiddine, Karine Reynaud, Svetlana Uzbekova, Danielle Monniaux

{"title":"The crazy ovary 2: a tribute to Ken McNatty.","authors":"Philippe Monget, Rozenn Dalbies-Tran, Jean-Jacques Lareyre, Gabriel Livéra, Feriel Yasmine Mahiddine, Karine Reynaud, Svetlana Uzbekova, Danielle Monniaux","doi":"10.1093/biolre/ioaf282","DOIUrl":"10.1093/biolre/ioaf282","url":null,"abstract":"In 2021, Ken McNatty, Danielle Monniaux, and I published a review essay illustrating how ovarian folliculogenesis can sometimes be bizarre, amazing, or even almost incomprehensible. Examples included the mechanisms underlying intra- and inter-species differences in ovulation rates; the possibility of awakening human primordial follicles in vitro, maturing and fertilizing them to produce viable offspring; and a model in which inactivation of a single oocyte gene results in sterile mice with follicular growth blocked at the primary stage but normal steroid cyclicity maintained. The aim of this second essay is to present further examples of the extraordinary diversity of ovarian function across animal species and, where possible, to propose hypotheses that may explain them. These concern: 1) the presence of oogonial stem cells in the ovaries of invertebrates and non-mammalian vertebrates, and their very probable absence in mammals; 2) the many and varied strategies of ovarian development and oogenesis in teleosts; 3)the metabolic dialog between cumulus cells and oocytes across mammalian species; 4) the presence of numerous germline genes, specifically or even exclusively expressed in the mammalian oocyte, whose invalidation has no phenotypic consequence on fertility in the mouse; 5) the unique features of ovarian function in the dog, particularly the frequent presence of polyovular follicles and the distinctive mode of post-ovulatory oocyte maturation; and 6) the absence of an intra-ovarian dominance factor in mono-ovulating species, disproving an old hypothesis: the selection of a single follicle is instead due to a succession of negative and then positive feedback between follicles and the hypothalamic-pituitary axis. This essay is also a final tribute to Ken McNatty, who liked to say that the ovary could be crazy.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"708-721"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epididymal sperm maturation in mouse species with differing levels of sperm competition†. 不同精子竞争水平的小鼠附睾精子成熟。

IF 3 2区生物学

Biology of Reproduction Pub Date : 2026-03-16 DOI: 10.1093/biolre/ioaf269

Clara Agudo-Rios, Ana Sanchez-Rodriguez, Ingrid I D Idrovo, Juan Ángel Laborda-Gomariz, Ana J Soler, Anthony Valverde, Maria E Teves, Eduardo R S Roldan

{"title":"Epididymal sperm maturation in mouse species with differing levels of sperm competition†.","authors":"Clara Agudo-Rios, Ana Sanchez-Rodriguez, Ingrid I D Idrovo, Juan Ángel Laborda-Gomariz, Ana J Soler, Anthony Valverde, Maria E Teves, Eduardo R S Roldan","doi":"10.1093/biolre/ioaf269","DOIUrl":"10.1093/biolre/ioaf269","url":null,"abstract":"During epididymal transit, spermatozoa undergo crucial morphological, biochemical, and molecular modifications that enable the acquisition of motility, acrosomal remodeling, membrane reorganization, and chromatin stabilization, culminating in full maturation. This study investigated sperm motility, sperm head and acrosome remodeling, chromatin compaction (protamination), DNA integrity, and nuclear morphology in sperm collected from different epididymal regions (caput, corpus, and cauda) and the vas deferens in three closely related mouse species exhibiting varying levels of sperm competition. Using microscopy, fluorescent staining (Hoechst 33342, chromomycin A3), sperm chromatin structure assay (SCSA), and nuclear morphology software, we characterized these parameters. Results demonstrated a gradual acquisition of total and progressive motility from the caput onwards and a shift toward a more compacted acrosome, especially between corpus and cauda. Minor species-specific variations in nuclear shape and dimensions were observed. Chromatin compaction and DNA integrity significantly increased, evidenced by decreased chromomycin A3 positive cells and reduced DNA fragmentation indices (tDFI and HDS). A correlation between protamine status and DNA fragmentation appeared when data from all species were pooled. Mus musculus showed lower overall motility and a faster decline in loose acrosomes. M. spicilegus exhibited the most rapid sperm head compaction, whereas M. spretus had the highest sperm nuclear width and the lowest tDFI values. These findings reveal distinct changes in sperm maturation markers along the epididymis and suggest associations between these changes and sperm competition levels of these species. This enhances our understanding of sperm maturation mechanisms and may inform advances in reproductive technologies.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"905-918"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13017584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Overexpression of placenta-specific noncanonical imprinted genes causes placental enlargement in intersubspecific hybrid mice†. 亚种间杂交小鼠胎盘特异性非规范印迹基因的过表达导致胎盘增大。

IF 3 2区生物学

Biology of Reproduction Pub Date : 2026-03-16 DOI: 10.1093/biolre/ioaf259

Syun Tokita, Naomi Watanabe, Ayumi Hasegawa, Satoshi Funaya, Kento Miura, Shogo Matoba, Atsuo Ogura, Kimiko Inoue

{"title":"Overexpression of placenta-specific noncanonical imprinted genes causes placental enlargement in intersubspecific hybrid mice†.","authors":"Syun Tokita, Naomi Watanabe, Ayumi Hasegawa, Satoshi Funaya, Kento Miura, Shogo Matoba, Atsuo Ogura, Kimiko Inoue","doi":"10.1093/biolre/ioaf259","DOIUrl":"10.1093/biolre/ioaf259","url":null,"abstract":"Placental enlargement in somatic cell nuclear transfer-derived mice is attributed to biallelic expression of noncanonical (H3K27me3-dependent) imprinted genes owing to loss of imprinting (LOI). Here, we investigated whether a similar mechanism underlies placental enlargement in intersubspecific hybrids between BDF1 (Mus musculus domesticus) and HMI (M. m. castaneus) mice. Quantitative and allelic expression analyses revealed gene-specific LOI in (BDF1 × HMI)F1 placentas: Jade1 (Phf17) and Slc38a4 showed LOI in all placentas regardless of expression levels, whereas Gab1 and Sfmbt2 exhibited LOI only when expression levels were elevated. Notably, Jade1 and Slc38a4 also showed biallelic expression at lower levels in normal-sized (BDF1 × JF1 [M. m. molossinus])F1 placentas. Maternal knockout of Jade1, Slc38a4, Sfmbt2, or the Sfmbt2 miRNA cluster restored monoallelic expression and significantly reduced the weight of (BDF1 × HMI)F1 placentas, indicating that these genes were collectively responsible for placental enlargement in intersubspecific hybrid placentas. Transcriptomic analysis revealed that LOI of noncanonical imprinted genes occurred after implantation. These findings suggest that placental enlargement in (BDF1 × HMI)F1 hybrids is driven by overexpression of multiple noncanonical imprinted genes, resulting from LOI after implantation and additional hybrid-specific, yet unidentified, upregulation mechanisms.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1058-1069"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13016830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MicroRNAs associated with adenomyosis promote endometrial epithelial cell migration via MMP-2 and MMP-9 upregulation†. 与子宫腺肌症相关的microrna通过上调MMP-2和MMP-9促进子宫内膜上皮细胞迁移†。

IF 3 2区生物学

Biology of Reproduction Pub Date : 2026-03-16 DOI: 10.1093/biolre/ioaf231

Margherita Zipponi, Alessandra Camboni, Ramanaiah Mamillapalli, Hugh S Taylor, Marie-Madeleine Dolmans

{"title":"MicroRNAs associated with adenomyosis promote endometrial epithelial cell migration via MMP-2 and MMP-9 upregulation†.","authors":"Margherita Zipponi, Alessandra Camboni, Ramanaiah Mamillapalli, Hugh S Taylor, Marie-Madeleine Dolmans","doi":"10.1093/biolre/ioaf231","DOIUrl":"10.1093/biolre/ioaf231","url":null,"abstract":"Adenomyosis is a common gynecological disorder characterized by the presence of endometrial tissue in the myometrium, causing chronic pelvic pain and abnormal bleeding. Although dysregulated microRNAs (miRNAs) in stromal cells of adenomyosis patients have been implicated in disease-associated extracellular matrix (ECM) remodeling, their role in regulating endometrial epithelial cell (EEC) behavior remains poorly understood. This study investigated the effect of selected adenomyosis- and endometriosis-associated miRNAs on EEC migration and matrix metalloproteinase (MMP) expression. Ishikawa cells, a human endometrial epithelium-like cell line, were transfected with mimics and inhibitors of Let-7b, miR-451a, miR-125b, miR-7 and miR-150. Cell migration was assessed using wound healing assays. MMP-2 and MMP-9 mRNA expression were quantified by quantitative real-time polymerase chain reaction, while protein production and secretion were evaluated by enzyme-linked immunosorbent assay. Transfection with Let-7b-5p inhibitor and miR-451a, miR-125b-1 and miR-150 mimics significantly enhanced cell migration and led to increased MMP-2 and MMP-9 mRNA expression, intracellular protein levels and secretion. These findings suggest that these miRNAs promote EEC migration and ECM remodeling through MMP upregulation, pointing to a potential mechanism for lesion formation in adenomyosis. Future research should seek to validate these findings in primary EECs and explore the therapeutic potential of targeting miRNA-MMP pathways for adenomyosis treatment.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"827-834"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13017560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145494459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mutations of SOX30 are identified in azoospermic human patients and reduce sperm in mice†. 在无精子患者中发现SOX30突变，并在小鼠中发现精子减少。

IF 3 2区生物学

Biology of Reproduction Pub Date : 2026-03-16 DOI: 10.1093/biolre/ioaf258

Sen Ren, Niuniu Chen, Shuai Lu, Tian Leng, Zhenlong Kang, Chen Xu, Zhiming Xie, Shenglin Han, Chenyu Lu, Cheng Wang, Zhibin Hu, Changsong Lin, Yichun Guan, Yayun Gu, Lan Ye

{"title":"Mutations of SOX30 are identified in azoospermic human patients and reduce sperm in mice†.","authors":"Sen Ren, Niuniu Chen, Shuai Lu, Tian Leng, Zhenlong Kang, Chen Xu, Zhiming Xie, Shenglin Han, Chenyu Lu, Cheng Wang, Zhibin Hu, Changsong Lin, Yichun Guan, Yayun Gu, Lan Ye","doi":"10.1093/biolre/ioaf258","DOIUrl":"10.1093/biolre/ioaf258","url":null,"abstract":"Sox proteins constitute a family of transcription factors now thought to play essential roles in cell fate decisions and tissue regeneration. SOX30 is a testis-specific transcription regulator for activating the postmeiotic haploid gene program, and knockout of Sox30 results in defects in meiotic exit with an arrest at the early stage of round spermatids. Here, we aim to investigate the impact of human SOX30 mutagenesis on this transcriptional regulatory axis and its contribution to male infertility. Genetic screen of a cohort of 620 patients with non-obstructive azoospermia identified six heterozygous sequence variations in SOX30. Its coding region contains five missense mutations and one stop-gained mutation (Arg478*), which is predicted to lead to the production of a C-terminal truncated protein. In vitro functional evaluation shows that this C-terminal truncated SOX30 protein exhibits a dramatic loss of its protein association with the histone deacetylase HDAC3, and the missense mutation in the HMG domain reduces its DNA-binding ability. We chose to model the human P353S mutation, by generating Sox30P382S knock-in mice with a point mutation in the HMG domain of the mouse Sox30 gene. Sox30P382S mutants are fertile, but this P382S point mutation causes defects in the late stages of spermatocytes that reduce mature sperm. These results suggest SOX30 mutations may contribute to the risk of non-obstructive azoospermia in humans.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"893-904"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Obesity disrupts ovarian hemodynamics during the preovulatory and luteal phases in mice†. 肥胖对小鼠排卵期和黄体期卵巢血流动力学的影响

IF 3 2区生物学

Biology of Reproduction Pub Date : 2026-03-16 DOI: 10.1093/biolre/ioaf293

Justine M Galliou, Samantha R Greenspun, Hanxue Zhang, Rebecca M Williams, Yi A Ren

{"title":"Obesity disrupts ovarian hemodynamics during the preovulatory and luteal phases in mice†.","authors":"Justine M Galliou, Samantha R Greenspun, Hanxue Zhang, Rebecca M Williams, Yi A Ren","doi":"10.1093/biolre/ioaf293","DOIUrl":"10.1093/biolre/ioaf293","url":null,"abstract":"Ovulation failure accounts for >25% of infertility cases in reproductive-age women in the United States, with obese women three times more likely to experience anovulatory infertility. The mechanisms by which obesity impairs ovulation remain unclear. The preovulatory luteinizing hormone (LH) surge induces changes in ovarian vasculature crucial for ovulation. We hypothesized that obesity disrupts ovarian vascular function, contributing to impaired ovulation. Using Doppler ultrasonography, we assessed ovarian hemodynamics in adult normal-weight mice and two obese groups: high-fat diet (HFD) and Agouti viable Yellow (AvY) mice. Both obese groups had reduced ovulation rates following superovulation. In normal-weight mice, flow velocity in the ovarian vessels increases within the first hour following ovulation induction by human chorionic gonadotropin, whereas this increase was absent in obese mice. This change in velocity correlated with ovulation rates, suggesting its importance for ovulation success. Ovarian hemodynamics were disturbed in naturally cycling obese mice compared to normal-weight controls during diestrus. Immediately before ovulation induction, ovarian vasculature analysis through lectin labeling revealed an increased abundance of capillaries in HFD ovaries compared to AvY; transcriptomic analysis of granulosa cells and ovarian stroma identified differentially expressed genes involved in vascular development, extracellular matrix organization, and inflammation, all crucial for vascular function and ovulation. This study characterizes for the first time in vivo ovarian hemodynamics in normal-weight adult mice, and demonstrates disrupted ovarian hemodynamics in obese mice during the preovulatory and luteal phases. These findings pinpoint that improving ovarian vascular function could be a therapeutic target for enhancing ovulation in obese women.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"981-997"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel inducible Cre mouse model for genetic manipulation in nonciliated cells of efferent ductules†. 一种新的可诱导的Cre小鼠模型，用于对传出小管非纤毛细胞进行遗传操作。

IF 3 2区生物学

Biology of Reproduction Pub Date : 2026-03-16 DOI: 10.1093/biolre/ioag002

Qianqian Gong, Zhilin Dou, Zhuowen Lv, Xiaoyi Lin, Keyi Zhang, Ming Shao, Sen Wang, Xiaoyang Sun

{"title":"A novel inducible Cre mouse model for genetic manipulation in nonciliated cells of efferent ductules†.","authors":"Qianqian Gong, Zhilin Dou, Zhuowen Lv, Xiaoyi Lin, Keyi Zhang, Ming Shao, Sen Wang, Xiaoyang Sun","doi":"10.1093/biolre/ioag002","DOIUrl":"10.1093/biolre/ioag002","url":null,"abstract":"The efferent ductules (ED) function as essential conduits for spermatozoa transport from the rete testis to the epididymis. The nonciliated and ciliated cells within the efferent ductal epithelium are responsible for fluid reabsorption and stirring the luminal fluid to prevent sperm agglutination, respectively. Dysfunction in either cell type can result in obstructive azoospermia. To systematically investigate the molecular mechanisms underlying efferent ductal development and function, we successively developed two novel knock-in mouse models via CRISPR/Cas9-mediated insertion of Cre-P2A or CreERT2-P2A cassettes into the Adgrg2 locus, enabling Adgrg2 promoter-driven co-expression of endogenous Adgrg2 and Cre recombinase. Cre-active tissues were examined in Cre-positive males crossed to Rosa26LacZ or Rosa26tdTomato reporter mice. Adgrg2-Cre mice exhibited embryonic Cre activity, as evidenced by tdTomato fluorescence in embryonic ED, proximal epididymis, and precursor cells, while postnatal males showed widespread genetic recombination across multiple tissues. In contrast, in postnatal Adgrg2-CreERT2 males under tamoxifen administration, Cre activity was prominently present in nonciliated cells within the efferent ductule epithelium and proximal epididymis, with minimal activity in other tissues. These models provide precise tools for cell type- and stage-specific genetic manipulation, facilitating studies on efferent ductal development, fluid homeostasis, and obstructive male infertility. The Adgrg2-CreERT2 line, in particular, offers a unique platform for nonciliated cell-specific genetic studies. This study opens new avenues for understanding the genetic and molecular basis of male reproductive tract function and associated pathologies.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"919-932"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145910378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stable isotope labelling mass spectrometry analysis of isolated mouse sperm. 分离小鼠精子的稳定同位素标记质谱分析。

IF 3 2区生物学

Biology of Reproduction Pub Date : 2026-03-16 DOI: 10.1093/biolre/ioag022

George Dobson, Melanie Balbach

引用次数: 0

Efficient generation of single-copy transgenic mice using piggyBat transposase from the little brown bat Myotis lucifugus†. 利用小棕蝠Myotis lucifugus†的piggyBat转座酶高效产生单拷贝转基因小鼠。

IF 3 2区生物学

Biology of Reproduction Pub Date : 2026-03-16 DOI: 10.1093/biolre/ioaf235

Eiichi Okamura, Shoma Matsumoto, Hayate Suzuki, Yoko Tanimoto, Tra Thi Huong Dinh, Natsuki Mikami, Masanaga Muto, Tomoko Matsumoto, Fumihiro Sugiyama, Satoru Takahashi, Knut Woltjen, Seiya Mizuno, Masatsugu Ema

{"title":"Efficient generation of single-copy transgenic mice using piggyBat transposase from the little brown bat Myotis lucifugus†.","authors":"Eiichi Okamura, Shoma Matsumoto, Hayate Suzuki, Yoko Tanimoto, Tra Thi Huong Dinh, Natsuki Mikami, Masanaga Muto, Tomoko Matsumoto, Fumihiro Sugiyama, Satoru Takahashi, Knut Woltjen, Seiya Mizuno, Masatsugu Ema","doi":"10.1093/biolre/ioaf235","DOIUrl":"10.1093/biolre/ioaf235","url":null,"abstract":"Transgenic animals are invaluable tools in genetic studies, disease modeling, drug discovery, and biotechnology. However, the low efficiency of transgenic animal generation can be an obstacle to their application. Here, we report the generation of transgenic mice using PBatase, the piggyBat transposase from the little brown bat (Myotis lucifugus). PBatase exhibits detectable transposition activity in fertilized mouse eggs within a limited concentration range, although the overall activity was lower than that of PBase, the piggyBac transposase from the cabbage looper moth (Trichoplusia ni). Transgenic animals carrying low transgene copy numbers were successfully generated with high efficiency using PBatase, and the transgene was subsequently transmitted to the next generation. This technique will be useful for the generation of transgenic animals carrying single copies of a transgene.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"784-793"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13017672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anti-Müllerian hormone ameliorates uterine DNA damage response and prevents pregnancy complications in doxorubicin-treated mice†. 抗<s:1> lerian激素改善阿霉素治疗小鼠子宫DNA损伤反应并预防妊娠并发症

IF 3 2区生物学

Biology of Reproduction Pub Date : 2026-03-16 DOI: 10.1093/biolre/ioaf233

Ngoc Minh Phuong Nguyen, Alana M Mermin-Bunnell, Karine de Mattos, Josephine Cleverdon, Motohiro Kano, Maeva Chauvin, Philippe Godin, Aki Kashiwagi, Thy Duong, Nicholas Nagykery, Patricia K Donahoe, Marie-Charlotte Meinsohn, David Pepin

{"title":"Anti-Müllerian hormone ameliorates uterine DNA damage response and prevents pregnancy complications in doxorubicin-treated mice†.","authors":"Ngoc Minh Phuong Nguyen, Alana M Mermin-Bunnell, Karine de Mattos, Josephine Cleverdon, Motohiro Kano, Maeva Chauvin, Philippe Godin, Aki Kashiwagi, Thy Duong, Nicholas Nagykery, Patricia K Donahoe, Marie-Charlotte Meinsohn, David Pepin","doi":"10.1093/biolre/ioaf233","DOIUrl":"10.1093/biolre/ioaf233","url":null,"abstract":"Anti-Müllerian hormone is a promising fertoprotective agent, demonstrating particularly strong efficacy against doxorubicin-induced ovarian toxicity. However, the impact of chemotherapy on the uterus, and the potential benefits of anti-Müllerian hormone in this context, remain poorly understood. In this study, we characterized doxorubicin-induced uterine damage and assessed the fertoprotective effect of anti-Müllerian hormone co-treatment in mice. Acutely, doxorubicin treatment caused the accumulation of DNA damage in multiple uterine cell-types, including the myometrium, as evidenced by both increased γ-H2AX staining and upregulation of Cdkn1a, Trp53, and other downstream Trp53 pathway targets, both at the mRNA and protein levels. Anti-Müllerian hormone co-treatment counteracted these effects by reducing γ-H2AX-positive DNA damage lesion accumulation and by suppressing Trp53 and its downstream pathway. Furthermore, anti-Müllerian hormone co-treatment significantly reduced the incidence of doxorubicin-induced labor dystocia, a complication of parturition, in pregnancies following chemotherapy treatment. These findings suggest that, in addition to ovarian protection, anti-Müllerian hormone may have benefits in preserving myometrial integrity and long-term uterine function following chemotherapy, further supporting its therapeutic potential for fertility preservation in cancer patients receiving chemotherapy.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"855-870"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12643066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0