Biology of Reproduction最新文献

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From sperm to offspring: epigenetic markers for dairy herd fertility. 从精子到后代:奶牛繁殖力的表观遗传标记。
IF 3.1 2区 生物学
Biology of Reproduction Pub Date : 2025-03-29 DOI: 10.1093/biolre/ioaf056
Ying Zhang, Marc André Sirard
{"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}
引用次数: 0
Activity of KNDy Neurons and the Melanocortin System During Pubertal Development in Female Sheep.
IF 3.1 2区 生物学
Biology of Reproduction Pub Date : 2025-03-28 DOI: 10.1093/biolre/ioaf074
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
{"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}
引用次数: 0
Early identification of bovine pregnancy status and embryonic mortality†.
IF 3.1 2区 生物学
Biology of Reproduction Pub Date : 2025-03-28 DOI: 10.1093/biolre/ioaf066
Jeanette V Bishop, Aydin Guzeloglu, Tom Scheller, Joshua J Docheff, Carolina L Gonzalez-Berrios, Hana Van Campen, Terry M Nett, Abigail L Zezeski, Thomas W Geary, William W Thatcher, Thomas R Hansen
{"title":"Early identification of bovine pregnancy status and embryonic mortality†.","authors":"Jeanette V Bishop, Aydin Guzeloglu, Tom Scheller, Joshua J Docheff, Carolina L Gonzalez-Berrios, Hana Van Campen, Terry M Nett, Abigail L Zezeski, Thomas W Geary, William W Thatcher, Thomas R Hansen","doi":"10.1093/biolre/ioaf066","DOIUrl":"https://doi.org/10.1093/biolre/ioaf066","url":null,"abstract":"<p><p>Interferon-tau (IFNT) is produced by the trophectoderm cells in the bovine conceptus as early as Day 12 following fertilization. It was hypothesized that IFNT detection in blood, milk and/or cervical secretions could be used to diagnose pregnancy in lactating cows. Recombinant bovine (rb) IFNT was generated to produce goat and rabbit anti-rbIFNT polyclonal antibodies and an enzyme-linked immunosorbent assay (ELISA) for bIFNT was developed using these reagents. The IFNT ELISA did not cross-react with other type I or II IFNs and had a limit of detection of 50-100 pg/ml. The IFNT ELISA detected IFNT in external os cervical swabs from Days 15 to 25 post-AI, but did not detect IFNT in serum, plasma, or milk. The time for most accurately detecting IFNT in cervical fluid was Days 16-19 after AI. A custom bovine swab device used to collect cervical secretions reduced false negative rates to 5.5% (94.5% Sensitivity) in dairy cows on Day 17 and 0 to 3.4% (100 and 96.6% Sensitivity) in beef cows on Days 18 or 16, respectively. In summary, the detection of IFNT in cervical fluid by ELISA provides an accurate indication of pregnancy status in lactating dairy cows. Early identification of the non-pregnant cow allows re-insemination on Day 21 compared to waiting until ultrasound on Day ~32-39. Also, the detection of IFNT on Day 17 followed by loss of pregnancy detected by ultrasound on Day 32 provides a novel research tool for studying pregnancy loss caused by embryonic mortality.</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":"143741863","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}
引用次数: 0
Ovochymase 2 is a key regulatory factor modulating proteolytic pathways and sperm maturation in the mammalian epididymis. 输精管酶 2 是哺乳动物附睾中调节蛋白水解途径和精子成熟的关键调节因子。
IF 3.1 2区 生物学
Biology of Reproduction Pub Date : 2025-03-28 DOI: 10.1093/biolre/ioaf069
Katarzyna Kent, Kaori Nozawa, Antrix Jain, Anna Malovannaya, Thomas X Garcia, Martin M Matzuk
{"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}
引用次数: 0
Metformin alters liver metabolism to sustain egg production in the reproductively aging broiler breeder hen. 二甲双胍可改变肝脏代谢,以维持繁殖力衰老的肉用种鸡的产蛋量。
IF 3.1 2区 生物学
Biology of Reproduction Pub Date : 2025-03-28 DOI: 10.1093/biolre/ioaf072
Evelyn Anne Weaver, Nathan Patrick Connolly, Tae Hyun Kim, Ramesh Ramachandran
{"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}
引用次数: 0
Endoplasmic reticulum stress: an emerging therapeutic target for preeclampsia. 内质网应激:子痫前期的新兴治疗靶点。
IF 3.1 2区 生物学
Biology of Reproduction Pub Date : 2025-03-28 DOI: 10.1093/biolre/ioaf071
Mengting Chen, Yafang Jin, Xiaohui Cao
{"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}
引用次数: 0
Testing the function of PPP-family phosphatases modified by luteinizing hormone signaling in mouse ovarian follicles: an update. 测试小鼠卵泡中被黄体生成素信号改变的 PPP 家族磷酸酶的功能:最新进展。
IF 3.1 2区 生物学
Biology of Reproduction Pub Date : 2025-03-28 DOI: 10.1093/biolre/ioaf076
Jeremy R Egbert, Corie M Owen, Tracy F Uliasz, Deborah Kaback, Siu-Pok Yee, Laurinda A Jaffe
{"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}
引用次数: 0
RNA Splicing and Alternative Polyadenylation Profile during Sheep Zygotic Genome Activation.
IF 3.1 2区 生物学
Biology of Reproduction Pub Date : 2025-03-28 DOI: 10.1093/biolre/ioaf068
Mingtian Deng, Hua Yang, Ying Chen, Nasser Ghanem, Yingnan Yang, Xiaowei Chen, Zhang JinHao, Feng Wang, Liqin Wang, Yanli Zhang
{"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}
引用次数: 0
The role of cholesterol/ALKBH1/ITGA2B in thrombosis in the placental vessels of preeclampsia. 胆固醇/ALKBH1/ITGA2B在子痫前期胎盘血管血栓形成中的作用。
IF 3.1 2区 生物学
Biology of Reproduction Pub Date : 2025-03-28 DOI: 10.1093/biolre/ioaf067
Yingying Zhang, Eryun Zhang, Ling Li, Yongwei Ren, Jinqiu Zhang, Qiutong Zheng, Minya Sun, Shaojie Zhao, Yugui Cui, Ying Gu, Zhice Xu
{"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}
引用次数: 0
The role(s) of HE4 and other WAP factors for sperm functions and male urogenital diseases.
IF 3.1 2区 生物学
Biology of Reproduction Pub Date : 2025-03-26 DOI: 10.1093/biolre/ioaf063
Xiaolun Xu, Huaiyun Tang, Shuai Zhang, Lingjin Tuo, Lisha Tang, Shi-Wen Jiang
{"title":"The role(s) of HE4 and other WAP factors for sperm functions and male urogenital diseases.","authors":"Xiaolun Xu, Huaiyun Tang, Shuai Zhang, Lingjin Tuo, Lisha Tang, Shi-Wen Jiang","doi":"10.1093/biolre/ioaf063","DOIUrl":"https://doi.org/10.1093/biolre/ioaf063","url":null,"abstract":"<p><p>HE4 (human epididymis protein 4) is a secretory glycoprotein with protease inhibitor activity. HE4 is constitutively expressed in the epididymis, testis, prostate, and other male urogenital organs. By its overexpression in the lesion and serum of cancer patients, HE4 is used as a biomarker for patient triage prognosis and recurrent surveillance of gynecologic malignancies. Elevated seminal plasma levels of HE4 have been correlated to oligoasthenozoospermia, and genetic overexpression of HE4 gene in mice led to the development of small testis, Leydig cell hyperplasia, structural anomalies of seminiferous tubules, elevated serum testosterone level, and decreased male fecundity. Since proteases and their endogenous inhibitors are deeply involved in semen liquefaction and sperm maturation/capacitation, motility, acrosomal reaction and fertilization, HE4 and other WAP domain protease inhibitors may participate in the regulation of various sperm functions and male fertility. In addition, increasing data have implicated HE4 and other WAP domain factors such as SLPI in innate immunity and inflammation, and these factors may play a role(s) in male urogenital inflammatory disorders such as epididymitis, testitis and prostatitis. This review summarizes relevant observations from in vitro, in vivo and clinical studies, and analyzes the potential role(s) of HE4 in male infertility and other urogenital diseases. Critical issues concerning HE4 physiopathological functions, mechanisms as well as the current/future research efforts, are raised and discussed.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717917","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}
引用次数: 0
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