Junmei Fan, Junkun Zhang, Xingyu Bi, Pengfei Zhu, Jinbao Wang, Dan Su, Wenjing Shi, Yanling Liu, Huiping Liu, Xueqing Wu
{"title":"Upregulation of OTULIN Alleviated Recurrent Pregnancy Loss by Suppressing Trophoblast Dysfunction and NF-κB Signaling Pathway","authors":"Junmei Fan, Junkun Zhang, Xingyu Bi, Pengfei Zhu, Jinbao Wang, Dan Su, Wenjing Shi, Yanling Liu, Huiping Liu, Xueqing Wu","doi":"10.1002/mrd.70029","DOIUrl":"https://doi.org/10.1002/mrd.70029","url":null,"abstract":"<div>\u0000 \u0000 <p>Recurrent pregnancy loss (RPL) is one of obstetrical diseases with no effective therapy methods. Trophoblast cell dysfunction and inflammation induce embryo implantation insufficiency, thereby resulting in RPL. OTU deubiquitinase with linear linkage specificity (OTULIN) plays a role in regulating the immune response and cell death. However, the role of OTULIN in RPL remains unclear. Spontaneous abortion mouse model and lipopolysaccharide-treated HTR-8/SVneo cells were used to investigate the role of OTULIN in RPL. OTULIN expression was downregulated in the labyrinth trophoblast of RPL mice and LPS-treated trophoblast cells. The embryonic reabsorption rate was decreased in OTULIN-overexpressed spontaneous abortion mice, accompanied with the increase in placental/fetus weight ratio. OTULIN overexpression significantly inhibited apoptosis in vivo and in vitro, as evidenced by the decrease in the activity of caspase 3. The expression of pro-inflammatory cytokines was decreased with OTULIN overexpression. Moreover, OTULIN overexpression decreased p-IκBα/IκBα and p-p65/p65 ratio. The nuclear translocation of NF-κB was suppressed via OTULIN overexpression both in vivo and in vitro. Our study suggested that OTULIN deficiency might cause inflammation and trophoblast abnormalities in RPL. The supplementation with OTULIN might alleviate the development of RPL via inhibiting NF-κB mediated inflammation response.</p></div>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074460","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":"Correction to “Differential Expression of Splicing Factor Gene by Estrogen Receptor Activation Factor”","authors":"","doi":"10.1002/mrd.70031","DOIUrl":"https://doi.org/10.1002/mrd.70031","url":null,"abstract":"<p>Jacob, J., V. S. Krishnan, S. Sreeja, and R. V. Thampan. 2025. “Differential Expression of Splicing Factor Gene by Estrogen Receptor Activation Factor.” <i>Molecular Reproduction and Development</i> 92: e70023. https://doi.org/10.1002/mrd.70023.</p><p>In the originally published article, updated Figures 5, 6, and 9B were inadvertently left out of the article. The correct figures are included below.</p><p>We apologize for these errors.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.70031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939071","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}
Indrashis Bhattacharya, Lakshmi K. Nalinan, K. V. Anusree, Ahmed Saleel, Aditi Khamamkar, Souvik Dey
{"title":"Evolving Lessons on Metazoan Primordial Germ Cells in Diversity and Development","authors":"Indrashis Bhattacharya, Lakshmi K. Nalinan, K. V. Anusree, Ahmed Saleel, Aditi Khamamkar, Souvik Dey","doi":"10.1002/mrd.70027","DOIUrl":"https://doi.org/10.1002/mrd.70027","url":null,"abstract":"<p>Germ cells are pivotal for the continuation of biological species. The metazoan germline develops from primordial germ cells (PGCs) that undergo multiple rounds of mitotic divisions. The PGCs are specified by either maternal inheritance of asymmetrically polarized cytoplasmic mRNAs/proteins (found in roundworms, flies, fishes, frogs, and fowl) or via direct induction of epiblast cells from adjacent extraembryonic ectoderm in mammals. In all vertebrates, PGCs remain uncommitted to meiosis and migrate to colonize the developing gonadal ridge before sex determination. Multiple RNA-binding proteins (e.g., <i>Vasa</i>, <i>Dnd</i>, <i>Dazl</i>, etc.) play crucial roles in PGC identity, expansion, survival, and migration. Postsex determination in mouse embryos, <i>Gata4</i>, expressing nascent gonads, induces <i>Dazl</i> expression in newly arriving germ cells that supports retinoic acid–mediated induction of meiotic onset. This article briefly discusses the developmental events regulating the PGC specification and commitment in metazoans. We also highlight the recent progress towards the in vitro generation of functional PGC-like cells in rodents and humans.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932382","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}
Bo Li, Ni Jin, Jie Lu, Ming Wang, Jun Wang, Shuqiang Chen
{"title":"Decreased OGT Attenuates Endometrial Decidualization and Embryo Implantation by Affecting HIF-1α Stability","authors":"Bo Li, Ni Jin, Jie Lu, Ming Wang, Jun Wang, Shuqiang Chen","doi":"10.1002/mrd.70025","DOIUrl":"https://doi.org/10.1002/mrd.70025","url":null,"abstract":"<div>\u0000 \u0000 <p>Hypoxia-inducible factor 1-alpha (HIF-1α) is essential for glycolysis regulation. Its expression in the endometrium is significantly reduced in recurrent implantation failure (RIF), indicating that lower levels of HIF-1α may contribute to embryo implantation failure. O-GlcNAcylation is a dynamic posttranslational modification mediated by O-GlcNAc transferase (OGT), known to regulate HIF-1α in cancer cells. However, it remains unclear whether OGT affects glycolytic processes in uterine endometrial stromal cells (ESCs) and its potential role in embryo implantation. This study utilized In Vitro and In Vivo experiments to investigate the role of OGT in decidualization and embryo implantation, along with its underlying mechanisms. Our findings show that OGT expression is significantly reduced in the endometrium of patients with RIF. Additionally, OGT knockdown led to failed embryo implantation in mice. Further analysis revealed that OGT promotes decidualization by stabilizing HIF-1α, which enhances glycolytic activity. Inhibiting OGT resulted in insufficient decidualization among human ESCs. Moreover, our results indicate that OGT partially regulates CCL2 secretion by maintaining HIF-1α levels within human ESCs, which is essential for successful embryo implantation. Based on these findings, we propose that OGT represents a novel and promising therapeutic target for both the diagnosis and treatment of RIF.</p></div>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919392","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":"Transcriptome Analysis of Individual Ovine Oocytes and Preimplantation Embryos From In Vitro Fertilization Source","authors":"Hai-Jun Liu, Xiang-Yun Li, Cheng-Jun Huang","doi":"10.1002/mrd.70028","DOIUrl":"https://doi.org/10.1002/mrd.70028","url":null,"abstract":"<div>\u0000 \u0000 <p>In this study, we examine the transcriptional profiles of eight stages of preimplantation embryo development, from germinal vesicle (GV) oocytes to blastocysts, in in vitro fertilized sheep embryos using RNA sequencing. Between 12,744 and 15,539 genes were detected from the GV moving forward to blastocyst, with cluster analysis revealing two distinct clusters related to developmental stage. The largest change for differentially expressed genes (DEGs) numbers took place between 2- to 4-cell comparison and 4- to 8-cell comparison, with a c. 35-fold increase from 19 to 670 DEGs. This suggests that zygotic genome activation occurred at 8-cell stage in sheep. All the DEGs had gene ontology annotations in three classes, and these comprised 53 subclasses. Most of the pathways (89 of 93) were enriched through KEGG analysis of the DEGs, and the most enriched pathway was oxidative phosphorylation. The 2- and 16-cell stage embryos possessed the highest and lowest numbers, respectively, of single nucleotide polymorphisms and insertion-deletion markers. Five major types of alternative splicing were found. A total of 2361 transcription factor genes were mutually expressed among the eight developmental stages. The top five differential transcription factor protein families were Zf-C2H2, bHLH, Homeobox, Others, and HMG. This is the first study to investigate the transcriptional profiling of sheep preimplantation embryos at different developmental stages, and it displays a comprehensive transcriptome landscape in sheep oocytes and embryos.</p>\u0000 </div>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902859","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}
Julie Jacob, Vidya S. Krishnan, S. Sreeja, Raghava Varman Thampan
{"title":"Differential Expression of Splicing Factor Gene by Estrogen Receptor Activation Factor","authors":"Julie Jacob, Vidya S. Krishnan, S. Sreeja, Raghava Varman Thampan","doi":"10.1002/mrd.70023","DOIUrl":"https://doi.org/10.1002/mrd.70023","url":null,"abstract":"<div>\u0000 \u0000 <p>The functional role of estrogen receptor activation factor (E-RAF), a 66 kDa protein in mediating the biological actions of estrogen and progesterone in goat uterus, has been highlighted in this work. Here we report that E-RAF stimulates the expression of splicing factor gene, arginine/serine rich in goat uterine nuclei (GenBank Accession No. MT473439). cDNA subtractive hybridization method using nuclear run-on transcription assay was used to identify the differentially expressed genes. The upregulation of the splicing factor gene was demonstrated further using a PCR-based nuclear run-on transcription system. Confocal microscopic analysis has confirmed the endoplasmic reticulum as the primary site of intracellular location of E-RAF. The effect of estrogen and progesterone on the intracellular distribution of E-RAF and the molecular mechanisms that underlie the transport of E-RAF to nucleus in the presence of progesterone has been studied. Our results offer a new perspective in steroid hormone action in uterus.</p>\u0000 </div>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801517","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":"Transcription Factor FOXD3 Regulates ELAV1/TLR4 Axis in Antiphospholipid Syndrome to Mediate Proliferation and Migration of Trophoblasts","authors":"Xiaolan Huang, Lingling Qiu, Suzhen Huang, Danhong Liang, Xiaoqing Chen","doi":"10.1002/mrd.70021","DOIUrl":"https://doi.org/10.1002/mrd.70021","url":null,"abstract":"<div>\u0000 \u0000 <p>This study focused on exploring the mechanism of transcription factor FOXD3 promoting the proliferation, migration, and invasion of trophoblast through ELAV1/TLR4 axis. The placenta villi from pregnancy patients with antiphospholipid syndrome (APS) and pregnancy controls were collected, along with the HTR-8/SVneo cell lines were obtained to detect the FOXD3, ELAV1, and TLR4 expressions using qRT-PCR and western blot. The interaction of ELAV1 with TLR4 mRNA was verified using RNA immunoprecipitation. The binding of FOXD3 with ELAV1 was detected using Chromatin Immunoprecipitation and dual luciferase reporter gene assay. After cell transfection, the cell proliferation, cell cycle distribution, invasion, and migration of the HTR-8/SVneo cell line were also measured. FOXD3, ELAV1, and TLR4 were elevated in the placenta villi of APS patients. TLR4 knockdown can promote the proliferation, invasion, and migration ability of HTR-8/SVneo cells. ELAV1 can bind TLR4 mRNA and increase its stability. TLR4 overexpression can inhibit the promotive effect of ELAV1 knockdown on HTR-8/SVneo cell biological functions. FOXD3 can bind the ELAV1 promoter and increase its transcription level to mediate HTR-8/SVneo cell biological functions. FOXD3 can bind and increase ELAV1 expression to stabilize TLR4 mRNA level, thereby increasing TLR4 expression and inhibiting the proliferation, invasion, and migration ability of trophoblast.</p>\u0000 </div>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741553","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":"Otud6a Knockout Leads to Male Subfertility in Mice","authors":"Fulin Yang, Zhuangfei Wang, Danyang Li, Fei Gao, Xiaohui Hou","doi":"10.1002/mrd.70022","DOIUrl":"https://doi.org/10.1002/mrd.70022","url":null,"abstract":"<div>\u0000 \u0000 <p>Ovarian tumor ubiquitinating 6A (OTUD6A) is a deubiquitinating enzyme whose aberrant expression has been linked to various diseases, including inflammation and prostate cancer. Research indicates that deubiquitinating enzymes (DUBs) play a significant role in spermatogenesis in mice. However, the role of OTUD6A in spermatogenesis remains unclear. To investigate the function of OTUD6A in mouse spermatogenesis, we generated <i>Otud6a-</i>knockout mice using the CRISPR/Cas9 system. Our results showed that OTUD6A is predominantly expressed in the testis and localized to the cytoplasm of spermatogonia and spermatocytes. Although no significant differences were observed in testicular size or morphology between <i>Otud6a-</i>knockout and wild-type mice, the knockout mice exhibited increased germ cell apoptosis, decreased epididymal sperm counts, abnormalities in sperm motility and subfertility. These findings indicate that <i>Otud6a-</i>knockout leads to male subfertility in mice.</p></div>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698892","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":"Paternal Effects in Mammalian Reproduction: Functional, Environmental, and Clinical Relevance of Sperm Components in Early Embryos and Beyond","authors":"Keith E. Latham","doi":"10.1002/mrd.70020","DOIUrl":"https://doi.org/10.1002/mrd.70020","url":null,"abstract":"<p>In addition to widely recognized contributions of the paternal genome, centriole, and oocyte-activation factors, sperm deliver a wide range of macromolecules to the fertilized embryo. The impacts of these factors on the embryo, progeny, and even subsequent generations have become increasingly apparent, along with an understanding of an extensive potential for male health and environmental exposures to exert both immediate and long-term impacts on mammalian reproduction. Available data reveal that sperm factors interact with and regulate the actions of oocyte factors as well as exerting additional direct effects on the early embryo. This review provides a summary of the nature and mechanisms of paternal effects in early mammalian embryos, long-term effects in progeny, susceptibility of sperm components to diverse environmental factors, and potential approaches to mitigate adverse effects of such exposures.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.70020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689905","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":"Decoding Müllerian Duct Epithelial Regionalization","authors":"Shuai Jia, Fei Zhao","doi":"10.1002/mrd.70018","DOIUrl":"https://doi.org/10.1002/mrd.70018","url":null,"abstract":"<p>Müllerian ducts (MD), also known as paramesonephric ducts, are the primordial anlage of the female reproductive tract organs including the oviduct, uterus, cervix and upper vagina along the craniocaudal axis. Although the general architecture of MD-derived organs is conserved, each organ possesses their unique epithelial structures and cell types to confer their region-specific functions, which collectively coordinate successful fertilization and pregnancy. MD epithelial fate decisions and differentiation along the craniocaudal axis is dependent on spatiotemporal regulation of intrinsic transcription factors and extrinsic signals derived from the mesenchyme. Findings from genetic mouse models, single-cell sequencing studies, and organoid cultures have significantly advanced our understanding of the cellular and molecular mechanisms of MD regionalization. In this review, we first discuss the diversity of epithelial morphologies and cell types in the female reproductive tract organs. Then, we discuss the roles of key transcription factors (<i>Hox</i>, transcriptional cascade driving multiciliogenesis, <i>Foxa2</i>, and <i>P63</i>), signaling pathways (estrogen/ESR1, Wnt/β-catenin, hedgehog, and retinoic acid), and epigenetic factors (microRNAs, chromatin remodeling factors, and histone modification enzymes) in region-specific MD differentiation. Further deciphering molecular mechanisms of MD craniocaudal patterning will open new avenues to improve our strategies for prevention, diagnosis, and treatment of Müllerian anomalies and female reproductive tract disorders.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481550","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}