Biology of Reproduction最新文献

{"title":"The MMP2 and MMP9-Specific Inhibitor SB-3CT Significantly Decreases Blood Pressure in Pre-eclampsia Model Rats.","authors":"Bowei Li, Jianfang Luo, Wanxing Zhou","doi":"10.1093/biolre/ioaf075","DOIUrl":"https://doi.org/10.1093/biolre/ioaf075","url":null,"abstract":"<p><p>Although uterine matrix metalloproteinases (MMPs) are known to play a role in the development of pre-eclampsia (PE), it remains unclear whether increased levels of serum MMPs are the pathogenesis underlying pregnancy-induced hypertension (PIH). We aimed to investigate whether the serum levels of MMP2 and MMP9 play a role in PIH using a specific inhibitor, SB-3CT. Twenty-five nine-week-old pregnant rats were randomly divided into five groups: normal pregnancy (SHAM) group, PE (RUPP) group, as well as low, middle, and high-dose intervention groups. The intervention groups received continuous intraperitoneal injections of SB-3CT at 25 mg, 50 mg, or 75 mg/kg/d doses. The SHAM and RUPP groups were injected with equal doses of solvent. Seven days later, the arterial pressure was tested at the carotid artery and rats were sacrificed. Serum MMP2, MMP9, tissue inhibitor of metalloproteinase-1 (TIMP1), endothelin-1 (ET-1), angiotensin II (AngII), and endothelial nitric oxide synthase (eNOS) levels were tested by ELISA. Vascular wall changes in cross-sections of the aorta abdominalis were observed using H&E-staining and the activities of MMP2 and MMP9 in the aorta abdominalis were tested using gelatin zymography. There were significant increases in blood pressure, serum MMP2 and MMP9 levels, and activities of MMP2 and MMP9 in the aorta abdominalis, along with notable vascular remodeling in the RUPP group. After the SB-3CT intervention, increased blood pressure was relieved and vascular remodeling improved, while MMP2 and MMP9 levels and activities were reduced. In summary, specific inhibition of MMP2 and MMP9 can decrease blood pressure in a PIH model. This indicates that increased MMP2 and MMP9 in maternal serum might contribute to the pathogenesis of PIH.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750891","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":"Heat stress during maturation of bovine oocytes profoundly impacts the mitochondrial bioenergetic profile and causes ER-stress in subsequent blastocysts.","authors":"Eva Held-Hoelker, Lientje Sophie Haake, Jessica Kurzella, Maibritt Schreiber, Christina Dauben, Dessie Salilew-Wondim, Nasser Ghanem, Franca Rings, Christine Große-Brinkhaus, Ernst Tholen, Dawit Tesfaye, Michael Hoelker","doi":"10.1093/biolre/ioaf070","DOIUrl":"https://doi.org/10.1093/biolre/ioaf070","url":null,"abstract":"<p><p>In dairy cows, detrimental effects of global warming and intensive genetic selection for high milk yield on reproductive performance have become increasingly relevant in cooler regions. Based on the current knowledge we hypothesized that elevated temperature during oocyte maturation affects mitochondria and endoplasmic reticulum in parallel with mitochondrial dysfunction representing the mechanistic link between ROS and ER Stress. To proof that, the present study aimed to uncover the consequences of heat stress during oocyte maturation on mitochondrial health, cellular oxidative stress response and its implications for endoplasmic reticulum stress (ER-stress). Immature bovine oocytes were matured either under routine temperatures (38.8°C, Control) or exposed to elevated temperatures (41°C, HS). MII oocytes as well as subsequent blastocysts were analysed in terms of developmental capacity, mitochondrial membrane potential, the bioenergetic profile, ROS level as well as expression of candidate genes playing a role in oxidative stress, endoplasmic reticulum stress and apoptosis. While no effect on matured oocytes became obvious, HS embryos demonstrated typical alterations of the mitochondrial bioenergetic profile in terms of higher mitochondrial membrane potentials not going along with higher ATP-linked oxygen consumptions and significantly lower maximum respiration and spare capacity rates implicating less efficient mitochondria accompanied with significantly higher ROS levels. Moreover, gene expression of HS embryos supported the assumption that mitochondria are the mechanistic link between oxidative stress and endoplasmic reticulum stress, impairing early embryo development by promoting apoptosis. In summary, the present study contributes to the elucidation of the multiple negative effects of heat stress during the maturation process.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750889","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":"From sperm to offspring: epigenetic markers for dairy herd fertility.","authors":"Ying Zhang, Marc André Sirard","doi":"10.1093/biolre/ioaf056","DOIUrl":"https://doi.org/10.1093/biolre/ioaf056","url":null,"abstract":"<p><p>In recent years, the study of bovine sperm epigenetics has garnered increasing attention alongside research on biomarkers associated with dairy cattle fertility. Male gametes not only transmit the paternal haploid genome to the offspring through fertilization, but also convey epigenetic components, such as DNA methylation, small non-coding RNA, histone variants, and histone modifications to offspring. This epigenetic information may transmit an acquired phenotype leading to intergenerational inheritance. The ongoing worldwide decline in dairy herd fertility affecting both males and females causes significant economic losses for dairy farmers. Previous scientific efforts to address this issue primarily targeted genetic aspects, identifying numerous fertility-related QTLs (Quantitative trait locus) and SNPs (Single nucleotide polymorphisms). However, since fertility is influenced by genetic, epigenetic, and environmental factors, this review highlights the importance of identifying sperm epigenetic markers as additional tools for evaluating and predicting cattle fertility.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742022","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":"Activity of KNDy Neurons and the Melanocortin System During Pubertal Development in Female Sheep.","authors":"Eliana G Aerts, Max J Griesgraber, Ashleigh L Thomson, Malori B Brown, Elizabeth C Bowdridge, Steven L Hardy, Andrew D Seman, Robert L Goodman, Casey C Nestor, Stanley M Hileman","doi":"10.1093/biolre/ioaf074","DOIUrl":"https://doi.org/10.1093/biolre/ioaf074","url":null,"abstract":"<p><p>The increase in luteinizing hormone (LH) that elicits puberty in many species results from a decrease in sensitivity to estradiol (E2) negative feedback. The neural mechanisms underlying this change are unknown, but do not occur at the gonadotropin-releasing hormone (GnRH) neurons as they lack estrogen receptor-alpha (ERα). A potentially important area is the arcuate nucleus of the hypothalamus (ARC), where neurons coexpressing kisspeptin, neurokinin B (NKB), and dynorphin (KNDy neurons) reside. KNDy neurons express ERα and while our previous work indicated that KNDy cells were critical for puberty, immunopositive cell numbers went unchanged during development, raising the likelihood of additional neuronal inputs. Herein, we used ovariectomized ewes implanted with E2 at prepubertal, peripubertal, or postpubertal ages to examine whether activation of KNDy neurons changed in association with increased LH secretion. Further, a potential role for the melanocortin system (proopiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons) was assessed. Activation of KNDy neurons increased with increased LH secretion. POMC cell numbers were unchanged, but activation of POMC cells and number of POMC-positive contacts onto KNDy neurons increased with age. In contrast, AgRP cell numbers and activity decreased. In addition, the percentage of POMC and AgRP neurons expressing Erα did not change. Thus, puberty-related increases in LH secretion are associated with activation of KNDy neurons and POMC neurons, but reduced activation and decreased numbers of AgRP neurons. To this point, no predictable changes in ERα expression within KNDy, POMC, or AgRP cell populations have been noted.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741860","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":"Ovochymase 2 is a key regulatory factor modulating proteolytic pathways and sperm maturation in the mammalian epididymis.","authors":"Katarzyna Kent, Kaori Nozawa, Antrix Jain, Anna Malovannaya, Thomas X Garcia, Martin M Matzuk","doi":"10.1093/biolre/ioaf069","DOIUrl":"https://doi.org/10.1093/biolre/ioaf069","url":null,"abstract":"<p><p>Spermatozoa acquire fertilizing competence during epididymal transit through proteolytic, chaperone-mediated, and post-translational modifications. Ovochymase 2 (OVCH2), an epididymis-specific trypsin-like serine protease, has emerged as a central regulator of this maturation process. Here, we integrate targeted gene disruption, comprehensive proteomic profiling, and affinity-based proteome enrichment to delineate how OVCH2 influences sperm functionality. Deletion of Ovch2 disrupts the proteome of epididymal sperm, resulting in diminished levels of core fertility-related factors-including a disintegrin and metalloprotease domain 3, β-defensins, and protease-inhibitor complexes-while inducing compensatory upregulation of alternate proteases and chaperones. Interaction assays confirm direct or indirect associations of OVCH2 with sperm surface proteins critical for fertilization, highlighting both its essential protease domain and the transient, finely regulated nature of its substrates. Collectively, these findings position OVCH2 as an orchestrator of sperm surface remodeling, with broad implications for fertility diagnostics and therapeutic interventions. By revealing a multifaceted network of OVCH2-dependent pathways, this study provides a mechanistic framework for developing innovative strategies to counter idiopathic male infertility and to enhance male contraceptive design.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742024","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":"Metformin alters liver metabolism to sustain egg production in the reproductively aging broiler breeder hen.","authors":"Evelyn Anne Weaver, Nathan Patrick Connolly, Tae Hyun Kim, Ramesh Ramachandran","doi":"10.1093/biolre/ioaf072","DOIUrl":"https://doi.org/10.1093/biolre/ioaf072","url":null,"abstract":"<p><p>The liver is critical in avian reproduction as it is the primary site of de novo lipogenesis and yolk precursor synthesis. Broiler breeder hens, the parents of commercial broiler chickens, have poor reproductive efficiency due to declining egg production from 45 weeks of age. We found that metformin increases fertile egg production in the aging broiler breeder hen, which was correlated with reduced body weight, reduced fat pad weight and altered reproductive hormone profiles. This study aimed to characterize the liver transcriptome of the same broiler breeder hens supplemented with metformin in the diet at 0 or 75 mg/kg body weight for 40 weeks (25-65 weeks of age; n = 45 hens/treatment). Liver tissue was collected from a subset of hens (n = 12 hens/treatment group) at 65 weeks of age, and RNA was extracted and sequenced using next-generation sequencing. Differential gene abundance analysis revealed that metformin treatment led to significant changes in gene expression. Further transcriptomic analysis highlighted increased expression of genes related to estrogen-stimulated yolk precursor synthesis, insulin-stimulated de novo lipogenesis, and AMPK-mediated glucose homeostasis. Quantitative PCR analysis revealed increased expression of ESR1, APOB, APOV1, VTG2, ADIPOQ, ADIPOR2 and ACACA mRNA and decreased expression of PCK1 mRNA while plasma triglyceride and non-esterified fatty acid levels were lower in metformin-treated animals compared to controls. The present study suggests that metformin supplementation supports prolonged egg production in aging broiler breeder hens by sustaining yolk precursor and fatty acid synthesis that are typically diminished in aging broiler breeder hens.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742023","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":"Endoplasmic reticulum stress: an emerging therapeutic target for preeclampsia.","authors":"Mengting Chen, Yafang Jin, Xiaohui Cao","doi":"10.1093/biolre/ioaf071","DOIUrl":"https://doi.org/10.1093/biolre/ioaf071","url":null,"abstract":"<p><p>Preeclampsia (PE), a common obstetric complication during pregnancy, has a global prevalence of 5-8% and is one of the leading causes of adverse maternal and fetal outcomes, which has a lack of effective treatment other than termination of pregnancy. Endoplasmic reticulum stress (ERS) is a self-stress response of cells to alleviate misfolded and unfolded protein aggregation and calcium ion homeostasis disorders in the ER lumen by activating the unfolded protein response. Many studies have demonstrated a potential link between ERS and PE pathogenesis by mediating genetic susceptibility, placental hypoxia, oxidative stress, metabolic disorders, impaired angiogenesis and function, and inflammatory responses. This article systematically describes the ERS mechanisms and their association with the pathological progression of PE. It also emphasizes that ERS can be a potential therapeutic target for PE clinical management.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742021","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":"Testing the function of PPP-family phosphatases modified by luteinizing hormone signaling in mouse ovarian follicles: an update.","authors":"Jeremy R Egbert, Corie M Owen, Tracy F Uliasz, Deborah Kaback, Siu-Pok Yee, Laurinda A Jaffe","doi":"10.1093/biolre/ioaf076","DOIUrl":"https://doi.org/10.1093/biolre/ioaf076","url":null,"abstract":"","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742026","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":"RNA Splicing and Alternative Polyadenylation Profile during Sheep Zygotic Genome Activation.","authors":"Mingtian Deng, Hua Yang, Ying Chen, Nasser Ghanem, Yingnan Yang, Xiaowei Chen, Zhang JinHao, Feng Wang, Liqin Wang, Yanli Zhang","doi":"10.1093/biolre/ioaf068","DOIUrl":"https://doi.org/10.1093/biolre/ioaf068","url":null,"abstract":"<p><p>Zygotic genome activation (ZGA) is a critical biological step in mammalian early embryo development. However, ZGA initiation in sheep and the related sophisticated RNA metabolism remains largely unknown. Here, we observed extensive alterations in gene expression and DNA methylation patterns, along with elevated levels of RNA polymerase II (RNAPII) and its phosphorylation at serine 2 (RNAPII-Ser2P) at the 16-cell stage. Moreover, the embryos were blocked at the 16-cell stage embryo when treated with α-Amanitin, indicating that ZGA is initiated at the 16-cell stage in sheep in vitro fertilized embryos. To uncover the sophisticated RNA metabolism during ZGA, we conducted weighted gene co-expression network analysis and identified 1957 critical maternal genes, including TET3, UHRF1 and KIF2C. Using dapars analysis, we discovered 1058 and 933 lengthened alternative polyadenylation (APA) events during ZGA in sheep and mice. Specifically, genes exhibiting shorten APA were highly expressed at sheep 16-cell stage embryos and mouse 2-cell stage embryos. During ZGA in sheep and mice, 2675 and 1963 genes showed exon skipping, an alternative splicing (AS) events, which is related to RNA binding, translation, gamete generation, and reproduction. Of note, inhibition of AS led to 2-cell block in mice and 8/16-cell block in sheep. Moreover, 5-EU, RNAPII, and RNAPII-Ser2P signal were decreased in AS inhibited 2-cell embryos in mice, suggesting AS might regulate the ZGA process by crosstalk with RNAPII. In conclusion, our data confirmed ZGA initiation at the 16-cell stage embryos, and provides insights into the complex RNA metabolism during ZGA in mammals.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742025","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 role of cholesterol/ALKBH1/ITGA2B in thrombosis in the placental vessels of preeclampsia.","authors":"Yingying Zhang, Eryun Zhang, Ling Li, Yongwei Ren, Jinqiu Zhang, Qiutong Zheng, Minya Sun, Shaojie Zhao, Yugui Cui, Ying Gu, Zhice Xu","doi":"10.1093/biolre/ioaf067","DOIUrl":"https://doi.org/10.1093/biolre/ioaf067","url":null,"abstract":"<p><p>The risk of multiple placental thrombosis is significantly elevated in preeclampsia (PE), and the vascular endothelium plays a vital role in coagulation processes through the secretion of ITGA2B, vWF, and TF. However, the underlying pathological mechanisms remain unclear. In this study, placental blood vessels were collected from both PE and normal pregnancies. Protein levels of ITGA2B were found to be up-regulated in PE samples compared to controls, indicating enhanced coagulation function in PE placental tissue. Additionally, Higher cholesterol levels of plasma and lower ALKBH1 expression in placental blood vessels of PE were found, overall DNA N6-methyldeoxyadenosine (6 mA) levels were up-regulated. Interestingly, the DNA 6 mA level at the ITGA2B promoter was decreased. Cholesterol overload experiments in human umbilical vein endothelial cells (HUVECs) demonstrated that cholesterol regulates the protein expression of ALKBH1 and ITGA2B in a concentration-dependent manner. Furthermore, ITGA2B protein expression was increased following ALKBH1 knockout, but no changes were observed when cholesterol was incubated with ALKBH1 knockout cells. These findings provide critical insights into the roles of cholesterol levels, ALKBH1, and ITGA2B in coagulation function within placental blood vessels. This information may contribute to further investigations of potential therapeutic targets and early prevention strategies for placental thrombosis in PE.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742027","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}