Biology of Reproduction最新文献

{"title":"Maternal high-fat, high-sucrose diet-induced excess adiposity is linked to placental hypoxia and disruption of fetoplacental immune homeostasis in late gestation.","authors":"Christian J Bellissimo, Tatiane A Ribeiro, Erica Yeo, Patrycja A Jazwiec, Howard Luo, Jaskiran Bains, Dawn M E Bowdish, Deborah M Sloboda","doi":"10.1093/biolre/ioaf143","DOIUrl":"https://doi.org/10.1093/biolre/ioaf143","url":null,"abstract":"<p><p>Maternal excess adiposity (i.e. overweight and obesity) at conception is linked to numerous signs of malperfusion and inflammatory injury in the placenta. Previous reports have suggested that obesity-associated placental malperfusion may trigger a state of fetoplacental hypoxia, possibly contributing to adverse health outcomes within and beyond the perinatal period. However, direct comparisons of tissue oxygen saturation at the uteroplacental interface in pregnancies complicated by excess adiposity are lacking. Here, we used a mouse model of chronic preconception high-fat, high-sucrose (HFHS) diet feeding to model the impacts of an obesogenic milieu on placental oxygenation near term gestation (E17.5). We found that both placental junctional and labyrinth zone tissues were hypoxic in HFHS pregnancies compared to chow-fed controls (CON). However, this was not associated with enhanced HIF-1α expression in labyrinth tissues. Similarly, placentas from CON and HFHS dams did not exhibit any gross differences in morphology, vessel density, or pericyte coverage. However, HFHS placentas had a greater burden of histopathological lesions, including tissue calcification and fibrinoid deposition within the labyrinth zone. Calcified placental tissue coincided with the destruction of vasculosyncytial membranes and macrophage-dense foci, alongside altered expression of immunomodulatory and chemotactic cytokines within the labyrinth zone proteome, which differed in magnitude with fetal sex. While fetal growth was not markedly affected, fetuses from HFHS pregnancies exhibited higher levels of circulating IL-6, prolactin, CXCL1, and CCL2. Collectively, these data confirm that diet-induced maternal excess adiposity leads to a reduction in placental oxygen saturation, even in the absence of marked growth restriction or fetal demise. While this hypoxic state was not linked to gross morphological abnormalities, it was associated with a greater histopathological burden indicative of local malperfusion and inflammation, and an altered fetal inflammatory and endocrine milieu in late gestation. These findings provide new insight into mechanisms by which an obesogenic environment during pregnancy compromises placental function and contributes to the long-term programming of chronic disease susceptibility.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574794","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":"Progress of sex control techniques in mammals.","authors":"Hongyu Chen, Hossam E Rushdi, Juan J Loor, Zhanwei Teng, Shenhe Liu","doi":"10.1093/biolre/ioaf149","DOIUrl":"https://doi.org/10.1093/biolre/ioaf149","url":null,"abstract":"<p><p>Sex control techniques enable the production of offspring of a specific sex in animals. Methods for achieving sex control in mammals generally fall into two categories: (1) spermatozoa processing pre-fertilization and (2) early embryo sexing after fertilization. This paper reviews and compares spermatozoa processing pre-fertilization based on the physical and chemical characteristics of X and Y spermatozoa, including various sperm separation methods. Early embryo sexing techniques after fertilization are classified into invasive and non-invasive methods. These include karyotyping, polymerase chain reaction (PCR) based on Y chromosome-specific genes, loop-mediated isothermal amplification (LAMP) based on the specific sequence of Y chromosome, fluorescence in situ hybridization (FISH) based on a Y-chromosome-specific DNA probe, H-Y antigen detection, X-linked enzymes detection, metabolomics based on the spent culture medium of the embryo, and non-invasive genetic reporter labeling of sex chromosomes. The use of ligands to activate the TLR7/8 signaling pathway in the immunological separation are also reviewed as a potential method for sperm separation. Overall, novel molecular and cell biology methods are enabling the development of sex control technologies, which can positively impact animal production.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574795","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":"TULP2, a substrate of CCT8, is essential for the intraflagellar transport during spermiogenesis in mice.","authors":"Wenhua Xu, Chuan Xu, Lu Yuan, Changmin Niu, Fan Yang, Tingting Ge, Guanghua Li, Yichun Zhao, Jieyu Zhao, Ying Zheng","doi":"10.1093/biolre/ioaf147","DOIUrl":"https://doi.org/10.1093/biolre/ioaf147","url":null,"abstract":"<p><p>Male infertility is a significant global health challenge. We previously found that TUB like protein 2 (TULP2), a member of the TULPs family, is indispensable for male fertility. In this study, we demonstrate the essential role of TULP2 in sperm function, including capacitation, acrosome reaction, and fertilization. Mechanistic investigations revealed TULP2 as a critical coordinator of protein transport during spermatogenesis. Specifically, TULP2 interacts with several intraflagellar transport (IFT) components, and quantitative analyses revealed significant dysregulation of some IFT-related molecules including IFT20, IFT80, IFT70A, BBS7, DYNLT2B, and HDAC6 in Tulp2-/- mice. Furthermore, localization analyses revealed pronounced abnormalities in the distribution of IFT20 in both testicular spermatids and spermatozoa, while IFT70A and IFT80 mislocalization was specifically observed in spermatozoa of Tulp2-/- mice. Our findings reveal that the apical domain of chaperonin containing TCP1 subunit 8 (CCT8) appears to recognize and interact with TULP2. Knockdown of CCT8 results in the formation of TULP2 aggregates in the cytoplasm, thereby impairing its function in ciliogenesis. We identified a homozygous missense variant in TULP2 (c.C832>T [p.R278W]) in one individual with asthenoteratozoospermia. Interestingly, the sperm flagella of this individual exhibited abnormalities that closely resembled those observed in KO mice. Overall, we propose that TULP2, as a CCT8 substrate, is a crucial protein for sperm function and may regulate spermatogenesis through its interactions with IFT components.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558938","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 metritis and systemic antibiotic treatment on the biology and morphology of the bovine uterus at one month postpartum†.","authors":"Monica O Caldeira, Joao G N Moraes, Thao T Nguyen, Josiane C C Silva, Isabella Sellmer Ramos, Scott E Poock, Thomas E Spencer, Matthew C Lucy","doi":"10.1093/biolre/ioaf146","DOIUrl":"https://doi.org/10.1093/biolre/ioaf146","url":null,"abstract":"<p><p>The biology and morphology of the uterus was explored at approximately one month postpartum for cows that were diagnosed with metritis (uterine disease; n=18) or healthy (n=17) at 7 to 10 d postpartum and either treated or untreated with ceftiofur hydrochloride (2x2 factorial). Cows were slaughtered at one month postpartum and the uterine horns were flushed to identify cows with a purulent or clear (non-purulent) content. RNA was isolated from caruncular (CAR) and inter-caruncular (ICAR) endometrium for RNA sequencing. Light microscopy was used to quantify inflammation and scanning electron microscopy (SEM) was used to assess the closure of the luminal surface of the uterus and the morphology of uterine glands. Results were that postpartum antibiotic treatment did not affect the endpoints that were measured including gene expression and morphology of the uterus. The primary biological driver of uterine function and morphology was inflammation at one month postpartum (endometritis; purulent material in the uterine lumen). Inflammation decreased epithelial growth factor signaling pathway expression (Wnt, Hippo, and Hedgehog) and biological processes involved in the formation of ciliated cells. Based on morphology, epithelial cells closed open areas of a denuded uterine surface using a process that involved depolarization and cell movement (planar cell polarity). Non-canonical Wnt signaling drives planar cell polarity and the loss of Wnt signaling may explain the slower tissue repair in cows with endometritis. Future studies and therapeutic treatments should consider uterine involution as a process of wound repair and tissue regeneration in the face of bacterial infection.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558937","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":"miR-423-3p inhibits CTNNBIP1/WNT preventing hyperandrogenic PCOS.","authors":"Shanshan Zhang, Yajing Liu, Mingming Wang, Donata Ponikwicka-Tyszko, Slawomir Wolczynski, Li Chen, Xuan Huang, Bing Yao, Nafis A Rahman, Xiangdong Li","doi":"10.1093/biolre/ioaf116","DOIUrl":"https://doi.org/10.1093/biolre/ioaf116","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) lacks the generally accepted diagnostic biomarkers and targeted therapy. Increasing evidence indicates that microRNAs (miRNAs) play a crucial role in PCOS. Hereby, we tested the functional implications of a novel miRNA (miR-423-3p) as a mediator in the progress of hyperandrogenic PCOS, as well as its potential as a new serum biomarker and therapeutic target for the PCOS. We found significantly decreased miR-423-3p levels in serum, granulosa cells (hGCs), and follicular fluid (FF) of PCOS patients (n = 40) compared to healthy controls (n = 30), and this decrease corroborated in PCOS-like mouse models. The receiver operating characteristic (ROC) curve analysis for circulating miR-423-3p indicated high diagnostic potential as a biomarker, with an area under the curve (AUC) of 82%. miR-423-3p influenced human granulosa cell (KGN) proliferation by directly targeting CTNNBIP1 modulated WNT signaling pathway. We further proved as mechanistic role that the elevated dihydrotestosterone (DHT) inhibited the expression of miR-423-3p via the activation of the androgen receptor, and the overexpression of miR-423-3p normalized the function of androgen-induced GCs. While we overexpressed miR-423-3p, it counteracted androgen-induced dysfunction in GCs. Antiandrogen treatment restored the reproductive phenotypes in letrozole-induced PCOS-like mice and regulated miR-423-3p expression and its downstream effects. Ovarian intrabursal injection of miR-423-3p antagomir in wildtype (WT) mice induced PCOS-like phenotypes, further underscoring its functional role. Our results demonstrated that miR-423-3p emerged as a novel mediator in hyperandrogenic PCOS progression and it holds promise as both a diagnostic biomarker and a therapeutic target.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538009","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":"Control of bioenergetic balance in mouse spermatogonial stem cells by alanine metabolism.","authors":"Takehiro Miyazaki, Narumi Ogonuki, Mito Kanatsu-Shinohara, Takuya Yamamoto, Shogo Matoba, Atsuo Ogura, Takashi Shinohara","doi":"10.1093/biolre/ioaf144","DOIUrl":"https://doi.org/10.1093/biolre/ioaf144","url":null,"abstract":"<p><p>Although spermatogonial stem cells (SSCs) are considered to rely on glycolysis, they also require specific amino acids for self-renewal. Here we demonstrate a unique role of alanine in sustaining SSCs in vitro through pyruvate generation. Analysis of amino acid requirements in cultured SSCs revealed that alanine is indispensable for SSCs, even in the presence of glucose. Alanine deficiency induced Trp53-dependent apoptosis without affecting the fate commitment of SSCs. Ethanolamine rescued defective proliferation and increased pyruvate formation in alanine-deficient medium. Furthermore, alanine deficiency depleted pyruvate in cultured SSCs, indicating the necessity of alanine-to-pyruvate conversion for self-renewal. While lactate was dispensable, pyruvate maintained long-term SSC cultures through enhanced uridine metabolism. Offspring were born by microinsemination using sperm that developed from cultured SSCs sustained by supra-molar pyruvate. These results show the critical role of alanine in maintaining SSC bioenergetic balance via pyruvate production in vitro.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538008","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":"Phosphoproteomic profiling of Siberian sturgeon (Acipenser baerii Brandt, 1869) sperm: insights into cryopreservation-induced changes with DMSO and methanol†.","authors":"Mariola A Dietrich, Natalia Kodzik, Magdalena Bakun, Mirosław Szczepkowski, Andrzej Ciereszko","doi":"10.1093/biolre/ioaf128","DOIUrl":"https://doi.org/10.1093/biolre/ioaf128","url":null,"abstract":"<p><p>Semen cryopreservation is a crucial technique in aquaculture, enabling the long-term preservation of genetic material from endangered species such as the Siberian sturgeon (Acipenser baerii Brandt, 1869). While methanol (MeOH) and dimethyl sulfoxide (DMSO) similarly affect sturgeon semen quality post-thaw, DMSO significantly reduces hatching rates. Given our prior findings on cryoprotectant-specific differences in the sturgeon sperm proteome, we investigated the molecular basis of DMSO-induced dysfunction using label-free quantitative phosphoproteomics. In fresh sperm, 1649 phosphorylation sites were identified on 736 proteins, forming the most extensive database of phosphorylated sperm proteins in fish. Functional enrichment analysis showed these phosphoproteins were primarily involved in cilium organization, energy metabolism, spermatogenesis, transmembrane transport, vesicle-mediated transport, and sperm binding to the zona pellucida, predominantly localizing to cytoplasm, cilia, and mitochondria. Cryopreservation profoundly altered the phosphoproteome, with 269 phosphosites showing differential phosphorylation between fresh and cryopreserved samples. DMSO induced phosphorylation changes at 231 sites across 114 proteins, whereas MeOH affected 260 sites across 127 proteins. Distinct phosphorylation patterns were identified for each cryoprotectant, with shared alterations involving cilium assembly, glycolysis, phosphatidylinositol metabolism, chromatin structure, and ion channel regulation associated with impaired motility, membrane destabilization, and reduced acrosomal integrity. DMSO-specific changes disrupted nucleoporin structure and centriole organization while inhibiting Rho signaling, crucial for acrosomal reaction and actin filament dynamics, which likely contribute to low hatching outcomes. In contrast, MeOH uniquely enhanced AMPK signaling, promoting mitochondrial ATP buffering and energy homeostasis. This study provides the first comprehensive phosphoproteomic analysis of sturgeon sperm, linking DMSO-induced disruptions to impaired fertilization outcomes.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538010","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":"The TEX15 DUF3715 domain is required for retrotransposon silencing and male fertility†.","authors":"Fang Yang, N Adrian Leu, P Jeremy Wang","doi":"10.1093/biolre/ioaf142","DOIUrl":"https://doi.org/10.1093/biolre/ioaf142","url":null,"abstract":"","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526416","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":"Heterogeneity in somatic cell nuclear transfer embryo reprogramming across mammalian species†.","authors":"Weijian Li, Yalan Liu, Li Wang, Airixiti Dilixiati, Zhiyue Cheng, Zhanzhan Chang, Xiuling Ma, Zhi He, Yibai Liang, Yuhan Wang, Yuan Zhang, Xuguang Wang","doi":"10.1093/biolre/ioaf133","DOIUrl":"https://doi.org/10.1093/biolre/ioaf133","url":null,"abstract":"<p><p>Somatic cell nuclear transfer (SCNT) enables the reprogramming of terminally differentiated somatic cells into a totipotent state, yet whether this process is governed by conserved mechanisms across mammalian species remains poorly understood. Here, we employed low input transcriptomics to profile global transcriptional dynamics during zygotic genome activation in SCNT embryos from five species: mouse, pig, cattle, goat, and sheep. Our analysis revealed distinct genome-wide expression patterns among these species, with 70.17% of differentially expressed genes (DEGs) being species-specific, while only 9.17% were shared DEGs. Functional annotation of the shared DEGs highlighted their enrichment in processes such as mRNA transcription, translation, and carbohydrate metabolism. Notably, we observed widespread pathway overactivation in SCNT embryos from cattle, mouse, and pig, whereas goat and sheep SCNT embryos exhibited broad suppression. Furthermore, weighted gene co-expression network analysis (WGCNA) demonstrated that species-specific effects exerted a far greater influence on reprogramming outcomes than the method of embryo generation (Fertilization or SCNT). Through systematic identification of key transcription factors, signaling pathways, epigenetic markers, and alternative splicing events, we uncovered species-specific regulatory patterns underlying reprogramming. Additionally, genome browser analysis revealed regional chromosomal expression anomalies in GDF9 and BMP15 during reprogramming across species. Collectively, our findings provide critical insights into the divergent mechanisms of reprogramming in mammalian species and establish a robust theoretical foundation for future studies in this field.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526415","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 Selective Serotonin Reuptake Inhibitors (SSRI) on the Placenta†.","authors":"David T Ellenberger, Rosalind T B Herrington, Sarah E Seda, Alyssa N Lambert, Cheryl S Rosenfeld","doi":"10.1093/biolre/ioaf141","DOIUrl":"https://doi.org/10.1093/biolre/ioaf141","url":null,"abstract":"<p><p>The rate of depression in pregnant mothers has dramatically risen in the past few decades. One of the well-studied causes of depression is a deficiency of serotonin (5-HT) in the synaptic cleft of neurons in the central nervous system, called the serotonergic theory of depression. The serotonin transporter (SERT/SLC6A4) binds 5-HT such that it can no longer bind and activate its cognate receptors on the post-synaptic neurons. Greater number of pregnant women are prescribed a selective serotonin reuptake inhibitor (SSRI) drug to combat depression. These compounds act to bind to SERT, and thereby prolonging the duration 5-HT remains active within the synaptic cleft. While such treatments might be beneficial for the mother, the placenta and fetal brain can be inadvertently affected. SERT has been proposed to be the primary means by which the placenta internalizes maternal 5-HT and then transfers this neurotransmitter to the emerging brain, where it guides initial brain development. Herein, we consider evidence that SSRIs might influence the placenta-brain axis and contribute to gestational disorders, such as preeclampsia (PE), fetal growth restriction (FGR), and gestational diabetes (GDM). Current data with rodent models, in vitro approaches with human trophoblast cell lines, and human epidemiological studies are reviewed. Gaps in our current understanding and future directions are discussed. A better understanding of how SSRIs might affect the placenta is crucial as by obstructing acquisition of maternal 5-HT by the placenta and downstream alterations on fetal brain development, these treatments might impact the lifelong health of sons and daughters.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526401","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}