Biology of Reproduction最新文献

{"title":"Chorionic trophoblast cells demonstrate functionally different phenotypes from placental trophoblasts†.","authors":"Jaganmoy Choudhury, Lauren S Richardson, Rheanna Urrabaz-Garza, Jeena Jacob, Ananth Kumar Kammala, Ramkumar Menon","doi":"10.1093/biolre/ioaf003","DOIUrl":"10.1093/biolre/ioaf003","url":null,"abstract":"<p><p>Chorionic trophoblast cells are one of the principal components of the fetal membrane and join with the decidua to form a feto-maternal interface. Recent success in isolating chorionic trophoblast cells dealt with two separate questions: (i) the necessity of highly enriched and defined media with inhibitors of oxidative stress and cell transition and their impact on growth and trophoblast phenotype, (ii) the functional differences between chorionic trophoblast cells and other placental trophoblast lineages of cells (placental cytotrophoblast cells, and extravillous trophoblast). Chorionic trophoblast cells were cultured either in defined media with various inhibitors or in media from which inhibitors were removed individually. Cellular morphology and growth (microscopy and crystal violet staining) and cellular and molecular biological features (immunofluorescence staining for GATA-binding protein 3, cytokeratin 7, and vimentin) were assessed. Syncytialization of cells (forskolin treatment) and invasive properties of chorionic trophoblast cells (cell invasion assay) were tested and compared with placental cytotrophoblast cells and extravillous trophoblasts (HTR8/SVneo), respectively. Removal of various growth-supporting agents from the media delayed cell growth and inclined towards cellular transition (increase in vimentin compared to cytokeratin 7 or GATA-binding protein 3) compared to chorionic trophoblast cells grown in complete and enriched media. The chorionic trophoblast cells failed to syncytialize, contrasting with the high levels of membrane fusion observed in placental cytotrophoblast cells. Although chorionic trophoblast cells express human leukocyte antigen G like extravillous trophoblasts, they do not invade. Chorionic trophoblast cells require several specific constituents for in vitro growth and phenotype maintenance. Chorionic trophoblast cells are trophoblast lineage cells that barricade immune cell-enriched decidua without invading them. These properties support their location and function, which are distinct from placental cytotrophoblast cells and extravillous trophoblasts.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"530-539"},"PeriodicalIF":3.1,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930597","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}

{"title":"mTOR signaling mediates energy metabolic equilibrium in bovine and mouse oocytes during the ovulatory phase†.","authors":"Zaohong Ran, Ruiyan Liu, Hongru Shi, Xiaodong Wang, Zian Wu, Shanshan Zhou, Jianning Liao, Lichang Hu, Yongtao Hu, Jintao Zhou, Changjiu He, Xiang Li","doi":"10.1093/biolre/ioae182","DOIUrl":"10.1093/biolre/ioae182","url":null,"abstract":"<p><p>The mammalian target of rapamycin (mTOR) signaling pathway is activated by luteinizing hormone in preovulatory follicle. However, its impact on ovulation remains inadequately explored. Utilizing in vivo studies and in vitro fertilization, we demonstrated that the negative effect of inhibition of mTOR signaling by rapamycin on oocyte quality during the ovulatory phase, with a notable decrease in the total cell count of blastocysts, a reduction in gastrula size, and fetal degeneration on the 16th day of gestation while not affecting ovulated oocyte count or granulosa cell luteinization. Mechanistically, our study elucidated that in the ovulatory phase, mTOR signaling inhibition enhances lipid consumption, mitochondrial membrane potential of oocytes, and ATP generation. As a result, embryos derived from these oocytes exhibit higher levels of reactive oxygen species, insufficient energy supply, and lower developmental potency. Furthermore, the impact of mTOR signaling on oocytes remains consistent across various species, and its inhibition has been demonstrated to enhance energy metabolism during the in vitro maturation process of bovine oocytes. These findings demonstrate the critical role of mTOR signaling during the ovulatory phase in balancing oocyte energy metabolism, enriching our understanding of the role of mTOR on ovulation regulation.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"474-484"},"PeriodicalIF":3.1,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999562","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}

{"title":"Single-cell atlas of the pregnant equine endometrium before and after implantation†.","authors":"Joanna Jaworska, Dawid Tobolski, Shebl E Salem, Anne Kahler, Izabela Wocławek-Potocka, Amanda M de Mestre","doi":"10.1093/biolre/ioaf004","DOIUrl":"10.1093/biolre/ioaf004","url":null,"abstract":"<p><p>Embryo implantation in the mare occurs just over one month after fertilization, coinciding with the production of chorionic gonadotropin. The factors that regulate this late implantation in the mare, and whether they are unique to horses or shared with more invasive embryo implantation in other species, remain poorly understood. This study aimed to determine and compare the transcriptome and subpopulations of endometrial cells before and after embryo implantation in the horse. Single-cell RNA sequencing was used to characterize the transcriptome of nearly 97,000 endometrial cells collected from biopsies of the endometrium at the beginning (day 33 of gestation) and after embryo implantation (day 42 of gestation) in mares. Sixteen immune and 24 non-immune cell clusters were identified, representing known major cell populations as well as novel subpopulations of horse immune cells such as resident innate lymphoid cells and mucosal-associated invariant T cells. Contrary to current knowledge, endometrial natural killer (eNK) cells were the most abundant endometrial leukocyte population during implantation in horses. Moreover, eNK cells not only expressed genes that may interact with fetal MHC I, such as LY49F, but also exert immunoregulatory functions independent of MHC I expression, such as CD96/TIGIT. Analogous to other species studied, upregulation of CXCR4 was found in several subpopulations of immune cells. Our results suggest that despite distinctive and later placentation compared with humans, horses share some key similarities in the mechanisms of embryo implantation.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"458-473"},"PeriodicalIF":3.1,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930600","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}

{"title":"Impact of DNAH3 deficiency on sperm energy metabolism and motility leading to asthenozoospermia†.","authors":"Jinli Li, Yingdong Liu, Pengcheng Kong, Qiurong Chang, Siyu Chen, Wanli Yang, Wenqiang Liu, Xiaoming Teng, Yi Guo","doi":"10.1093/biolre/ioaf008","DOIUrl":"10.1093/biolre/ioaf008","url":null,"abstract":"<p><p>Asthenozoospermia, a prevalent contributor to male infertility, exhibits a multifaceted pathogenesis. This study identified a significant downregulation in sperm dynein heavy chain 3 (DNAH3) protein levels in individuals with asthenozoospermia. To elucidate the role of DNAH3 in asthenozoospermia, we constructed Dnah3-knockout mice, which exhibited asthenozoospermia and sterility. The sperm motility of Dnah3-knockout mice significantly declined compared to wild-type mice. However, spermatozoa from Dnah3-knockout mice displayed normal morphology in hematoxylin and eosin staining and transmission electron microscopy analyses. Sperm metabolomics revealed that DNAH3 deficiency disturbed sperm energy metabolism, resulting in substantial reductions of L-palmitoylcarnitine and glycocholic acid. Notably, offspring were successfully obtained from Dnah3-knockout male mice through intracytoplasmic sperm injection. Collectively, these findings indicate that DNAH3 deficiency induces disturbances in energy metabolism, rather than abnormalities in sperm flagellar morphology, culminating in asthenozoospermia development. Our investigation provides valuable insights into understanding asthenozoospermia and offers guidance for clinical consultation.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"501-512"},"PeriodicalIF":3.1,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944082","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}

{"title":"A deep learning tissue classifier based on differential co-expression genes predicts the pregnancy outcomes of cattle†.","authors":"Chenxi Huo, Chuanqiang Zhang, Jing Lu, Xiaofeng Su, Xiaoxia Qi, Yaqiang Guo, Yanchun Bao, Hongxia Jia, Guifang Cao, Risu Na, Wenguang Zhang, Xihe Li","doi":"10.1093/biolre/ioaf009","DOIUrl":"10.1093/biolre/ioaf009","url":null,"abstract":"<p><p>Economic losses in cattle farms are frequently associated with failed pregnancies. Some studies found that the transcriptomic profiles of blood and endometrial tissues in cattle with varying pregnancy outcomes display discrepancies even before artificial insemination (AI) or embryo transfer (ET). In the study, 330 samples from seven distinct sources and two tissue types were integrated and divided into two groups based on the ability to establish and maintain pregnancy after AI or ET: P (pregnant) and NP (nonpregnant). By analyzing gene co-variation and employing machine learning algorithms, the objective was to identify genes that could predict pregnancy outcomes in cattle. Initially, within each tissue type, the top 100 differentially co-expressed genes (DCEGs) were identified based on the analysis of changes in correlation coefficients and network topological structure. Subsequently, these genes were used in models trained by seven different machine learning algorithms. Overall, models trained on DCEGs exhibited superior predictive accuracy compared to those trained on an equivalent number of differential expression genes. Among them, the deep learning models based on differential co-expression genes in blood and endometrial tissue achieved prediction accuracies of 91.7% and 82.6%, respectively. Finally, the importance of DCEGs was ranked using SHapley Additive exPlanations (SHAP) and enrichment analysis, identifying key signaling pathways that influence pregnancy. In summary, this study identified a set of genes potentially affecting pregnancy by analyzing the overall co-variation of gene connections between multiple sources. These key genes facilitated the development of interpretable machine learning models that accurately predict pregnancy outcomes in cattle.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"550-562"},"PeriodicalIF":3.1,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999559","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}

{"title":"Mechanistic target of rapamycin signaling activity in the human placenta across gestation and in maternal obesity†.","authors":"Katie L Bidne, Kathryn E Erickson, Theresa L Powell, Thomas Jansson","doi":"10.1093/biolre/ioaf007","DOIUrl":"10.1093/biolre/ioaf007","url":null,"abstract":"<p><p>The mechanistic target of rapamycin system is vital to placental development, formation, and function. Alterations in this system in the placenta have been associated with altered fetal growth. However, changes in placental mechanistic target of rapamycin signaling across gestation are poorly understood. We collected 81 human placental samples from 4 to 40 weeks gestation to test the hypothesis that placental mechanistic target of rapamycin signaling activity increases over gestation and is activated in maternal obesity in early gestation. Proteins involved in upstream mechanistic target of rapamycin regulation and mTORC1/2 downstream signaling were quantified using immunoblotting in placentas of male or female fetuses. Readouts of mTORC1 activation, phospho-rpS6, and phospho-4EBP1 were highest in first trimester and decreased across gestation. Phosphorylation of AKT (308 and 473) increased over gestation. Interestingly, abundance of cytochrome c oxidase I and mitochondrial ATP synthase, key subunits of mitochondrial complexes III/IV and V, respectively, were elevated in first trimester obese placentas compared to control, but only in placenta from female fetuses. We suggest that the high placental mechanistic target of rapamycin signaling activity in early pregnancy may be related to the high anabolism and active trophoblast proliferation and invasion in the second half of the first trimester. In addition, we conclude that maternal obesity has only limited impact on this key placental signaling pathway across gestation in women.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"540-549"},"PeriodicalIF":3.1,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969470","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}

{"title":"Digital analysis of ovarian tissue: generating a standardized method of follicle analysis†.","authors":"Hannah McDowell, Isaac Vieco-Martí, Maya VanZanten, Shravya Pant, Hana Kubo, Diane C Saunders, Monica M Laronda, Sofía Granados-Aparici","doi":"10.1093/biolre/ioaf022","DOIUrl":"10.1093/biolre/ioaf022","url":null,"abstract":"","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"416-419"},"PeriodicalIF":3.1,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188049","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}

{"title":"Green tea polyphenols alleviate di (2-ethylhexyl) phthalate-induced testicular injury in mice via lncRNA-miRNA-mRNA axis†.","authors":"Heng Shi, Xin-Hai Zhao, Qin Peng, Xian-Ling Zhou, Si-Si Liu, Chuan-Chuan Sun, Qiu-Yu Cao, Shi-Ping Zhu, Sheng-Yun Sun","doi":"10.1093/biolre/ioae179","DOIUrl":"10.1093/biolre/ioae179","url":null,"abstract":"<p><p>Di(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer known for its toxic effects on the male reproductive system. Green tea polyphenols (GTPs), recognized for their antioxidant and anti-inflammatory properties, have demonstrated protective effects on various organs, but the mechanisms by which GTPs mitigate DEHP-induced testicular damage remain unclear. Healthy male C57BL/6J mice were divided into five groups: control, DEHP, DEHP + GTP treatment, GTP, and oil groups. Testicular histopathological changes were assessed using hematoxylin-eosin (H&E), periodic acid-Schiff (PAS), and Masson staining. Ultrastructural alterations were examined through transmission electron microscopy. High-throughput sequencing was performed to analyze the expression of mRNA, miRNA, and lncRNA and construct an lncRNA-miRNA-mRNA regulatory network for identifying key regulatory axes. Mice in the DEHP group exhibited significant testicular damage, including reduced sperm count, mitochondrial deformation, and endoplasmic reticulum dilation. GTP treatment notably improved testicular structural integrity, restored sperm count, and alleviated mitochondrial and endoplasmic reticulum damage. Additionally, DEHP significantly increased activated CD8+ T cells, which were reduced with GTP treatment. High-throughput sequencing revealed that GTP treatment exerted protective effects through the regulation of six key lncRNA-miRNA-mRNA axes. GTPs significantly protect against DEHP-induced testicular damage, and the lncRNA-miRNA-mRNA regulatory axes play a potential role in this process.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"485-500"},"PeriodicalIF":3.1,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806075","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}

{"title":"Effects of endometrial embryokines on the preimplantation bovine embryo to create a gene expression signature consistent with a high competence phenotype†.","authors":"Mariângela Bueno Cordeiro Maldonado, Maria Belen Rabaglino, Gabrielle Heather Cannon, Peter James Hansen","doi":"10.1093/biolre/ioaf014","DOIUrl":"10.1093/biolre/ioaf014","url":null,"abstract":"<p><p>Optimal embryonic development depends upon cell-signaling molecules released by the maternal reproductive tract called embryokines. The identity of specific embryokines that enhance the competence of the embryo for sustained survival is largely lacking. The current objective was to evaluate the effects of three putative embryokines in cattle on embryonic development to the blastocyst stage. The molecules tested were vascular endothelial growth factor A (VEGFA), C-X-C motif chemokine ligand 12 (CXCL12), and interleukin-6 (IL6). Molecules were added from day 4 to 7.5 of culture at 50 ng/mL (VEGFA and CXCL12) or 100 ng/mL (IL6). Endpoints were development to the blastocyst stage and transcript abundance for 94 specific genes involved in lineage commitment, epigenetic regulation, and other functions. Among the genes examined were eight whose transcript abundance has been related to embryo competence for survival after embryo transfer. None of the molecules increased the proportion of putative zygotes or cleaved embryos becoming blastocysts at day 7.5 of development. An embryo competence index based on a Bayesian multiple regression formula to weigh transcript abundance of the eight biomarker genes was not affected by treatment with VEGFA but was increased by both CXCL12 and IL6. The transcript abundance of 5 genes was modified by VEGFA, 19 by CXCL12, and 19 by IL6. A total of 11 genes were modified in a similar manner by CXCL12 and IL6. Most differentially expressed genes for CXCL12 and IL6 were downregulated, suggesting that the embryokines may promote a less energetically demanding metabolic state than would be the case in their absence.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"447-457"},"PeriodicalIF":3.1,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051455","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}

{"title":"Utilization of the QuPath open-source software platform for analysis of mammalian spermatogenesis†.","authors":"Bryan A Niedenberger, Heather A Belcher, Emma A Gilbert, Matthew A Thomas, Christopher B Geyer","doi":"10.1093/biolre/ioaf011","DOIUrl":"10.1093/biolre/ioaf011","url":null,"abstract":"<p><p>The adult mammalian testis is filled with seminiferous tubules, which contain somatic Sertoli cells along with germ cells undergoing all phases of spermatogenesis. During spermatogenesis in postnatal mice, male germ cells undergo at least 17 different nomenclature changes as they proceed through mitosis as spermatogonia (=8), meiosis as spermatocytes (=6), and spermiogenesis as spermatids (=3). Adding to this complexity, combinations of germ cells at each of these stages of development are clumped together along the length of the seminiferous tubules. Due to this, considerable expertise is required for investigators to accurately analyze changes in spermatogenesis in animals that have spontaneous mutations, have been genetically modified (transgenic or knockout/knockin), or have been treated with pharmacologic agents. Here, we leverage our laboratory's expertise in spermatogenesis to optimize the open-source \"Quantitative Pathology & Bioimage Analysis\" software platform for automated analyses of germ and somatic cell populations in both the developing and adult mammalian testis.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"583-599"},"PeriodicalIF":3.1,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999563","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}