Katheryn D Peterson, Trevor F Freeman, Shankar P Poudel, Susanta K Behura, D Kakhniashvili, Daniel L Johnson, Tulio M Prado, Lew G Strickland, Jonathan E Beever, Thomas E Spencer, Daniel J Mathew
{"title":"Unraveling the elongating bovine conceptus microenvironment: identification of gene transcripts and proteins along the conceptus-maternal interface in cattle†.","authors":"Katheryn D Peterson, Trevor F Freeman, Shankar P Poudel, Susanta K Behura, D Kakhniashvili, Daniel L Johnson, Tulio M Prado, Lew G Strickland, Jonathan E Beever, Thomas E Spencer, Daniel J Mathew","doi":"10.1093/biolre/ioaf002","DOIUrl":"10.1093/biolre/ioaf002","url":null,"abstract":"<p><p>The bovine conceptus elongates near Day 16 of development and releases interferon-tau, disrupting the endometrial luteolytic mechanism to sustain luteal P4 and pregnancy. Conceptus factors other than interferon tau modify local endometrial activities to support pregnancy; however, the microenvironment is largely uncharacterized. We utilized a bovine conceptus-endometrial culture system to elucidate the microenvironment in the form of gene transcripts and protein. Estrus synchronized heifers remained cyclic (13) or were inseminated (9) to produce Day 16 cyclic endometrium and elongating conceptuses, respectively. Conceptus sections and endometrium were then used to generate tissue cultures in 1 ml of medium: (i) no tissue (control med; n = 7), (ii) mono-cultured conceptus (conceptus; n = 9) (iii) mono-cultured endometrium (endo; n = 13), or (iv) endo-conceptus co-culture (n = 15). After 12 h, tissue gene transcripts were sequenced (RNA-Seq) and media underwent proteomic analysis (LC-MS/MS). Compared to conceptus and endo, co-cultured conceptus and endometrial tissue contained 3400 and 4575 differentially expressed genes, respectively (P ≤ 0.01). More abundantly expressed endometrial differentially expressed genes were associated with interferon signaling whereas more abundantly expressed conceptus differentially expressed genes were associated with protein homeostasis and metabolism (FDR < 0.001). When co-culture media where compared to endo media, 288 more abundant proteins were identified (P < 0.05). Biological processes related to these proteins included antigen presentation via MHC Class Ib and keratinization (FDR < 0.001). Within the mono-cultured conceptus and endometrial media, folate receptor alpha (FOLR1; P < 0.001) was identified as the most abundant secreted protein suggesting the reproductive tissues elicit a microenvironment supportive of conceptus growth involving folate metabolism.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"513-529"},"PeriodicalIF":3.1,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944083","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}
Leticia T Casarotto, Helen N Jones, Pascale Chavatte-Palmer, Geoffrey E Dahl
{"title":"Review: Placental physiology and fetal programming in ruminants under heat stress.","authors":"Leticia T Casarotto, Helen N Jones, Pascale Chavatte-Palmer, Geoffrey E Dahl","doi":"10.1093/biolre/ioaf047","DOIUrl":"https://doi.org/10.1093/biolre/ioaf047","url":null,"abstract":"<p><p>The placenta plays a crucial role in transferring nutrients and oxygen between the dam and fetus during pregnancy. It is highly influenced by environmental conditions, especially stressors such as heat and nutritional deficiencies, which can significantly impact the fetus's long-term health and development. Cattle, especially dairy cows, commonly experience stress during late gestation, which can lead to changes in behavior and physiology, affecting both subsequent milk production and fetal development. Heat stress is one of the most common stressors experienced by mammals, and recent evidence suggests a role in the programming of the dam and fetus. This review explores different hypotheses of fetal programming, including the Barker Hypothesis, which connects early-life malnutrition to metabolic diseases in adulthood, and the Silver-Spoon Hypothesis, which highlights the long-term benefits of optimal prenatal conditions. Furthermore, we consider heat stress programming as it relates to the concept of developmental origins of health and diseases (DOHaD). The DOHaD hypothesis suggests that epigenetic adaptations occur in fetal DNA as a response to environmental influences. The review also emphasizes the role of the mechanism associated with possible epigenetic effects in the placenta, mediating the effects of maternal stress on the fetus, impacting gene expression, placental structure, and nutrient transfer. Understanding these mechanisms is essential for enhancing dairy cattle management and minimizing the adverse effects of environmental stressors on animal health and productivity.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633416","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}
Savannah L Speckhart, Abigayle B Pollock, Kayla J Alward, Kayla Farrell, Mary A Oliver, Kiho Lee, Fernando H Biase, Alan D Ealy
{"title":"The interleukin-6 signal transducer receptor subunit is required for optimal in vitro bovine embryo development†.","authors":"Savannah L Speckhart, Abigayle B Pollock, Kayla J Alward, Kayla Farrell, Mary A Oliver, Kiho Lee, Fernando H Biase, Alan D Ealy","doi":"10.1093/biolre/ioaf006","DOIUrl":"10.1093/biolre/ioaf006","url":null,"abstract":"<p><p>This work explored whether bovine embryo development relies on signaling from the interleukin-6 (IL6) cytokine family. This was accomplished by interrupting IL6 signal transducer (IL6ST), the common beta-subunit receptor used by the IL6 family. One series of studies cultured in vitro-produced embryos with SC144, a pharmacological IL6ST inhibitor. Providing the inhibitor at a concentration that partially diminished IL6ST signaling reduced development to the 16-cell and blastocyst stages and reduced inner-cell-mass cell numbers. Inhibitor concentrations that completely blocked IL6ST signaling prevented blastocyst development. Another series of studies used CRISPR-Cas9 to disrupt IL6ST. Two electroporation approaches were used to introduce guide RNAs and Cas9 protein into one-cell in vitro-produced embryos. Editing efficiency was ≥82%. Targeting IL6ST did not affect cleavage but reduced development to the 16-cell and blastocyst stages. A reduction in inner-cell-mass cell numbers was detected, and disorganization of the inner cell mass was observed in approximately one-half of the IL6ST-targeted blastocysts. These observations indicate that embryo-derived IL6 family members that signal through IL6ST are needed to support normal in vitro bovine embryo development. These signals are needed by the 16-cell stage and for inner-cell-mass cell development at the blastocyst stage. There is also evidence that these signals support the overall cellular organization of the blastocyst.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"434-446"},"PeriodicalIF":3.1,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930644","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":"Oxidation of thiol groups in membrane proteins inhibits the fertilization ability and motility of sperm by suppressing calcium influx†.","authors":"Satohiro Nakao, Kazuki Shirakado, Kana Tamura, Reiri Koga, Mayumi Ikeda-Imafuku, Yu Ishima, Naomi Nakagata, Toru Takeo","doi":"10.1093/biolre/ioae183","DOIUrl":"10.1093/biolre/ioae183","url":null,"abstract":"<p><p>The redox state of thiol groups derived from cysteine residues in proteins regulates cellular functions. Changes in the redox state of thiol groups in the epididymis are involved in sperm maturation. Furthermore, the redox state of thiol groups in proteins changes during the process of sperm capacitation. However, the effect of the redox state of thiol groups in sperm membrane proteins on the fertilization ability of sperm has not been studied. Therefore, in this study, we oxidized thiol groups in sperm membrane proteins using 5,5-dithiobis-(2-nitrobenzoic acid) (DTNB), which is a thiol-selective oxidizing agent, and examined the effect of oxidation of these thiol groups on the fertilization ability of sperm. Oocytes and sperm were obtained from C57BL/6 J mice, and Jcl:ICR mice were used as recipients for embryo transfer. Oxidation of the thiol groups by DTNB decreased the in vitro fertilization rate, and removal of the zona pellucida recovered the fertilization rate. DTNB treatment decreased the amplitude of the lateral head, which is an indicator of hyperactivation, and suppressed an increase in the intracellular calcium ion concentration, which is essential for hyperactivation. These findings suggest that oxidation of thiol groups in sperm membrane proteins can decrease the fertility of sperm by suppressing calcium ion influx and hyperactivation.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"563-571"},"PeriodicalIF":3.1,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845787","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}
Arslan Tariq, Zachary K Seekford, John J Bromfield
{"title":"Inflammation during oocyte maturation reduces developmental competence and increases apoptosis in blastocysts†.","authors":"Arslan Tariq, Zachary K Seekford, John J Bromfield","doi":"10.1093/biolre/ioae180","DOIUrl":"10.1093/biolre/ioae180","url":null,"abstract":"<p><p>Uterine infections cause ovarian dysfunction and infertility. The bacterial endotoxin, lipopolysaccharide, accumulates in the follicular fluid of dominant follicles of cows with uterine infections. Granulosa cells produce an innate inflammatory response to lipopolysaccharide, altering the follicular microenvironment of the oocyte. We hypothesized that developmental competence and embryo quality would be reduced when oocytes are matured in an inflammatory environment. Bovine mural granulosa cells were exposed to either 1 μg/mL of lipopolysaccharide or medium alone for 24 h to produce a conditioned medium. Inflammatory responses of mural granulosa cells were confirmed by increased expression of CXCL8, IL1B, IL6, and TNF. Bovine cumulus-oocyte complexes were matured for 22 ± 1 h in a medium supplemented with either 1 μg/mL of lipopolysaccharide, 10% v/v conditioned medium of granulosa cells treated with either lipopolysaccharide (LCM) or medium alone, or no supplementation. In addition, polymyxin B (20 μg/mL) was added to the maturation medium to sequester LPS. Following maturation, cumulus-oocyte complexes were fertilized and cultured for 7.5 days with no further treatment. Oocyte maturation using lipopolysaccharide or LCM impaired development to the blastocysts stage, reduced the number of total and CDX2-negative blastomeres, and increased TUNEL-positive cells in blastocysts. Polymyxin B could rescue these effects in the lipopolysaccharide group but not in the LCM group, indicating factors produced by granulosa cells and not lipopolysaccharide alone compromised oocyte development. These findings suggest that the inflammatory milieu produced by granulosa cells in response to lipopolysaccharide impairs oocyte competence and the quality of resultant blastocyst-stage embryos.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"420-433"},"PeriodicalIF":3.1,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811999","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":"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}
Joanna Jaworska, Dawid Tobolski, Shebl E Salem, Anne Kahler, Izabela Wocławek-Potocka, Amanda M de Mestre
{"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}