Molecular human reproduction最新文献

{"title":"Temporal dynamics of uterine immune microenvironment remodeling in a murine model of adenomyosis.","authors":"Marlyne Squatrito, Julie Vervier, Laëtitia Bernet, Alessandra Camboni, Marie-Madeleine Dolmans, Carine Munaut","doi":"10.1093/molehr/gaaf057","DOIUrl":"10.1093/molehr/gaaf057","url":null,"abstract":"<p><p>Adenomyosis-the ectopic presence of endometrial glands and stroma within the myometrium-affects reproductive-age women and is associated with pain, bleeding, and subfertility, yet the immune events that precede pregnancy remain poorly defined. To address this, we investigated how the uterine immune microenvironment evolves before conception in a tamoxifen-induced murine model of adenomyosis. At 1- and 3-months post-induction, we analyzed uterine tissue by immunofluorescence, flow cytometry, and quantitative polymerase chain reaction. We found that adenomyotic uteri exhibited a sustained elevation of interleukin-6 messenger RNA, a transient interleukin-10 rise at 1 month, and stable cyclooxygenase-2 levels. Interleukin-6 receptor messenger RNA and signal transducer and activator of transcription 3 messenger RNA were both transiently downregulated at 1 month and returned to control levels by 3 months. Early in disease development, total macrophage numbers declined and displayed an alternative (M2) activation phenotype, followed by a selective loss of classically activated (M1) macrophages at later stages. B lymphocytes were consistently enriched, indicating enhanced humoral activity. Although overall T-cell counts remained stable, the CD3+ compartment underwent a marked shift from double-negative T lymphocytes toward T-helper and cytotoxic subsets, coinciding with the transient signaling changes. Limitations of our study include reliance on a single animal model, analysis at only two timepoints, and a lack of functional assessment of regulatory T cells. Future work should incorporate finer temporal profiling, single-cell transcriptomics, and validation in human tissues. These findings highlight dynamic innate-adaptive crosstalk as an early driver of adenomyosis pathology and suggest that targeting interleukin-6-mediated pathways may inform biomarker development and novel immunomodulatory interventions.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12714385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145636005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Concern: Oocyte-derived BMP15 but not GDF9 down-regulates connexin43 expression and decreases gap junction intercellular communication activity in immortalized human granulosa cells.","authors":"","doi":"10.1093/molehr/gaaf053","DOIUrl":"10.1093/molehr/gaaf053","url":null,"abstract":"","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":"31 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13395791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in non-essential testis-enriched genes for human and mouse spermatogenesis.","authors":"Chunjia Wei, Sibing Yi, Yaoqiong Liang, Yue-Qiu Tan, Chaofeng Tu","doi":"10.1093/molehr/gaaf052","DOIUrl":"10.1093/molehr/gaaf052","url":null,"abstract":"<p><p>Spermatogenesis is a highly complex cellular differentiation process. Recent advances employing knockout or knock-in mouse models have functionally characterized more than 700 genes as essential for male fertility maintenance. Paradoxically, emerging evidence reveals that a substantial proportion of the continuously expanding catalog of testis-enriched genes exhibits biological dispensability for normal sperm production. To systematically catalog non-essential testis-enriched genes in murine spermatogenesis, we performed a comprehensive PubMed literature review encompassing studies published up to 1 August 2025. Through stringent inclusion criteria, this analysis consolidates data from 83 publications that identified 261 testis-enriched genes demonstrated to be non-essential for spermatogenesis. We further categorize these genes by their familial relationships and explore potential explanations for the fertile phenotype observed in these knockout models, including genetic redundancy, compensatory mechanisms, differences in knockout strategies, and environmental influences. This review provides a valuable resource to avoid unnecessary expenditures and effort by research teams.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophils in the female reproductive tract: immune interactions and sperm adaptations.","authors":"Priksha Kuni, Gagan Kajla, Gagandeep Kaur Gahlay","doi":"10.1093/molehr/gaaf045","DOIUrl":"10.1093/molehr/gaaf045","url":null,"abstract":"<p><p>Human fertilization is a coordinated process involving interaction of sperm with the oocyte. As the sperm pass through the female reproductive tract (FRT), they are presented with numerous challenges. These include navigating through highly viscous cervical mucus while evading immune responses to successfully fertilize the oocyte. The female immune system facilitates sperm selection while providing protection against pathogens. Neutrophils, a major component of the innate immune system, use mechanisms such as phagocytosis, neutrophil extracellular trap formation, and trogocytosis to play a crucial role in this process. With the help of sialic acid residues and N glycans present on its glycocalyx as well as certain proteins in the seminal plasma, the sperm modulate the immune responses in the FRT to their advantage. This review examines the various interactions which take place between the sperm and the FRT, the neutrophil-mediated immune reaction occurring in the FRT, as well as the adaptations the sperm employ to overcome the immune challenges. Understanding these mechanisms provides critical insights into fertility and potential therapeutic targets for infertility.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphorylation of YWHAZ at Serine 58 by PKB/Akt is associated with resumption of meiotic arrest in mouse oocytes.","authors":"Jianchao Huo, Yifan Zhao, Zengyou Ma, Haoyi Zheng, Hui Peng","doi":"10.1093/molehr/gaaf056","DOIUrl":"10.1093/molehr/gaaf056","url":null,"abstract":"<p><p>Mammalian oocyte maturation is a tightly regulated process essential for successful fertilization and embryonic development. Meiotic resumption in mammalian oocytes is controlled by various regulatory factors, including the tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein (YWHA/14-3-3). However, the specific functions of individual YWHA isoforms in oocyte meiosis remain poorly understood. In this study, we revealed that knockdown of Ywhaz, one of the isoforms of YWHA, using short interfering RNA (siRNA) or morpholino oligomers (MOs), accelerates meiotic resumption in mouse oocytes. To elucidate the mechanism underlying YWHAZ-mediated meiotic resumption, we thus explored its interactions with potential target proteins. Co-immunoprecipitation and immunofluorescence analyses demonstrated a physical interaction between YWHAZ and phosphorylated CDC25B. Additionally, we identified the protein kinases responsible for YWHAZ phosphorylation at distinct residues. Specifically, JNK1, CSNK1A1/CKIα, and protein kinase B (PKB/Akt) were found to phosphorylate YWHAZ at Serine 184/186, Threonine 232, and Serine 58, respectively. Notably, phosphorylation of YWHAZ at serine 58 by PKB/Akt promoted meiotic resumption in mouse oocytes. Furthermore, we found the formation of a heterodimer between YWHAZ and YWHAQ. Our results provide insights into the PKB/Akt-YWHAZ-CDC25B signalling pathway and illuminate the functional influence of YWHAZ phosphorylation in meiotic regulation.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms of ligustilide in the treatment of low endometrial receptivity: involvement of desmoglein-2.","authors":"Dongjie He, Xingxing Ren, Jing Mao, Shaoqi Shi, Yanli Song, Huidongzi Xiao, Aiwu Wei","doi":"10.1093/molehr/gaaf043","DOIUrl":"10.1093/molehr/gaaf043","url":null,"abstract":"<p><p>We have previously shown that ligustilide (LIG) treatment can restore endometrial receptivity and promote implantation in pregnant rats with low endometrial receptivity (LER). Using mRNA sequencing technology, we found that desmoglein-2 (Dsg2) is one of the differentially expressed genes, which is downregulated in rats with LER but elevated after LIG treatment. DSG2 is an adhesion protein that exists in epithelial tissues and serves as a crucial component of the junction complex for intercellular adhesion. The ability to adhere between cells is considered essential for successful embryo implantation. Hence, we speculated that DSG2 might be involved in the mechanism by which LIG treats LER. Immunofluorescence staining, western blots, and immunohistochemical staining were performed to confirm the restored expression of DSG2 by LIG treatment in the endometrial tissues of LER rats. Then, we investigated the effect of DSG2 on endometrial receptivity by injecting small interfering (si)Dsg2 (for silencing Dsg2 expression) into one uterine horn of a pregnant rat and siNC (for a normal control) into the other. It was found that the side of the endometrium injected with siDsg2 showed significant changes in the expression of multiple receptivity-related molecules and obvious embryo loss. In addition, we found that these receptivity-related molecules were affected by siDsg2 in Ishikawa (an endometrial cell line) cells. Dsg2 knockdown reduced the ability of Ishikawa cells to adhere to trophoblastic spheroids. Furthermore, the effect of LIG on endometrial cell-trophoblast adhesion was partially abolished by Dsg2 silencing. In conclusion, our findings suggest that the protective effect of LIG against LER might be achieved by increasing DSG2 expression. DSG2 enhancement might become a novel strategy for the development of LIG-inspired treatments to improve endometrial receptivity.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin enhances vitrified mouse blastocyst development by mitigating oxidative stress and preserving mitochondrial function.","authors":"Dan Zhou, Qiaoyu Chen, Yunlong Bai, Mingming Ye, Yanping Jia, Xinyu Chen, Orhan Bukulmez, Li Meng, William Shu Biu Yeung, Robert J Norman, Wenqiang Liu, Miaoxin Chen","doi":"10.1093/molehr/gaaf054","DOIUrl":"10.1093/molehr/gaaf054","url":null,"abstract":"<p><p>This study aimed to investigate the benefits of melatonin supplementation during the blastocyst vitrification and thawing process and explore underlying mechanisms to prevent apoptotic events. We evaluated blastocysts in three groups: fresh blastocysts (Control), non-melatonin-treated vitrification (VT), and melatonin-treated vitrification (MVT). We compared their developmental potential and oxidative stress levels to analyse effects of optimized melatonin supplementation. Additionally, transcriptome analysis in blastocysts by Smart-seq2 was performed to investigate the underlying transcriptional mechanism. Antioxidant enzyme and mitochondrial function protein expression were investigated by immunofluorescence staining. Our results showed that supplementation of melatonin to the vitrification and warming solution significantly reduced the apoptotic cell proportion (P < 0.001) while increasing the numbers of inner cell mass (P < 0.001), trophectoderm (P < 0.001), and total cell counts (P < 0.001). Melatonin protected against oxidative stress and restored mitochondrial dysfunction in blastocysts, as evident from increased mitochondrial activity (P < 0.05) and reduced levels of Ca2+ (P < 0.05) and reactive oxygen species (P < 0.05). Importantly, melatonin alleviated cryodamage and preserved blastocyst ultrastructure, and rebalanced altered gene expression induced by the vitrification and warming. These results suggest that adding 10-10 M melatonin to vitrification and warming solutions protects mouse blastocysts against the detrimental effects of oxidative stress and enhances the efficiency of cryopreservation.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prophylactic treatment with progesterone decreases murine miscarriage by suppressing the immunostimulatory activity of macrophages.","authors":"Yuki Kaito, Hajime Ino, Yumi Horii, Asako Watanabe, Makoto Nishigaki, Yumene Kubota, Tomoko Ichikawa, Yasuyuki Negishi, Yoshimitsu Kuwabara, Rimpei Morita, Shunji Suzuki","doi":"10.1093/molehr/gaaf050","DOIUrl":"10.1093/molehr/gaaf050","url":null,"abstract":"<p><p>Miscarriage and preterm birth (PB) remain major challenges in obstetric care and are often associated with excessive inflammation at the feto-maternal interface. Although the role of progesterone (P4) in maintaining pregnancy is well known, its anti-inflammatory effects in immune-mediated pregnancy complications remain poorly understood. In this study, we investigated the impact of prophylactic P4 administration on miscarriage using a mouse model induced by α-galactosylceramide (αGC), a potent activator of invariant natural killer T (iNKT) cells. Prophylactic, but not therapeutic, P4 administration significantly reduced miscarriage rates. Flow cytometry analysis revealed that P4 suppressed the activity of iNKT cells and the production of inflammatory cytokines by these cells in the myometrium. Moreover, P4 reduced the immunostimulatory activity of antigen-presenting cells, particularly macrophages, by downregulating co-stimulatory molecules and interleukin (IL)-12 production. Immunohistochemistry and flow cytometry results demonstrated that the progesterone receptor (PR) was predominantly expressed on myometrial macrophages. Ex vivo experiments further confirmed that P4 directly modulates macrophage function, decreasing IL-12 and increasing IL-10 production. These findings suggest that prophylactic P4 administration mitigates immune activation at the feto-maternal interface by targeting macrophages, thereby suppressing iNKT cell-mediated inflammation and preventing miscarriage. This study highlights the importance of innate immune modulation in reproductive immunology and the potential of P4 as a prophylactic agent for preventing inflammation-associated miscarriage and PB.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WERF Endometriosis Phenome and Biobanking Harmonisation Project for Experimental Models in Endometriosis Research (EPHect-EM-Heterologous): heterologous rodent models.","authors":"M Louise Hull, Raul Gomez, Warren B Nothnick, Ruth Gruemmer, Katherine A Burns, Mohammed Zahied Johan, Isabella R Land, Stacey A Missmer, Lone Hummelshoj, Erin Greaves, Kaylon L Bruner-Tran","doi":"10.1093/molehr/gaaf022","DOIUrl":"10.1093/molehr/gaaf022","url":null,"abstract":"<p><p>Endometriosis, defined as the growth of endometrial-like tissues outside the uterus, is a common disease among women. Numerous in vivo rodent models of endometriosis have been developed to explore multiple aspects of this poorly understood disease. Heterologous models utilize human endometrial tissues engrafted into immunocompromized mice, while homologous models engraft rodent endometrium into immunocompetent mice or rats. Heterologous models of endometriosis more closely replicate the human disease; however, the murine humoral immune response must be suppressed to prevent rejection of the xenograft tissue. Although the innate immune system remains intact, suppression of the humoral response leads to a markedly different local and systemic immune environments compared to humans. Despite this limitation, experiments using heterologous models have contributed significantly to our understanding of endometriosis establishment and progression, the pre-clinical effectiveness of various therapeutic strategies, and genetically modifiable host factors that contribute to disease. Unfortunately, a lack of harmonization of the models used by different laboratories has impeded the reproducibility and comparability of results between groups. Therefore, the World Endometriosis Research Foundation (WERF) formed an international working group of experts in heterologous models of endometriosis to develop guidelines and protocols that could contribute to unifying experimental approaches across laboratories. Nine critical variables were identified: (i) mouse strain; (ii) human tissue type; (iii) hormonal status of the human tissue donor; (iv) human tissue preparation; (v) method and location of tissue placement; (vi) hormonal status of the recipient animal; (vii) whether or not mice were engrafted with human immune cells; (viii) endpoint assessments; and (ix) number and type of replicates. Herein, we outline important considerations for each major variable and make recommendations for unification of approaches. Widespread adoption of harmonized protocols and implementation of standardized documentation and reporting should further improve the reproducibility and translation of experimental findings both within and between laboratories.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":"31 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12237513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S14G-Humanin ameliorates ovarian dysfunction in a cyclophosphamide-induced premature ovarian insufficiency mouse model.","authors":"Jin Huang, Dandan Zhang, Liping Zou, Haoyuan Liu, Wei Xia, Changhong Zhu, Meng Rao","doi":"10.1093/molehr/gaaf042","DOIUrl":"10.1093/molehr/gaaf042","url":null,"abstract":"<p><p>Premature ovarian insufficiency (POI) is a major cause of female infertility, for which effective therapies remain limited. S14G-Humanin (HNG), a potent analogue of Humanin, exhibits strong antioxidant and anti-apoptotic properties and has demonstrated cytoprotective effects in various tissues, including the ovary. In this study, a cyclophosphamide (CP)-induced POI mouse model was established to evaluate both the ovarian damage induced by chemotherapy and the protective effects of HNG. HNG administration significantly increased the number of primordial follicles (P = 0.044) and growing follicles (all P > 0.05), as well as corpora lutea (P = 0.09). Moreover, HNG markedly improved oocyte quality (P = 0.009), significantly lowering the proportion of abnormal ovulated oocytes (P = 0.002). Fertility outcomes were also enhanced: CP treatment significantly reduced litter size compared to controls (4.6 ± 1.1 vs 8.0 ± 1.0; P < 0.001), whereas HNG treatment significantly mitigated this reduction (6.2 ± 0.8 vs 4.6 ± 1.1; P = 0.029). Mechanistically, HNG alleviated oxidative stress and apoptosis in ovarian tissues (all P < 0.05), reduced ROS levels (P = 0.034), and restored mitochondrial membrane potential (P = 0.004) in a human granulosa cell line. Furthermore, HNG significantly upregulated PGC-1α expression and enhanced AMPK phosphorylation in both in vivo and in vitro models (both P < 0.05). Collectively, these findings demonstrate that HNG confers significant protection against chemotherapy-induced ovarian damage and highlight its potential as a novel therapeutic agent for chemotherapy-induced ovarian damage.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}