Reproduction最新文献

{"title":"Elevated expression and reduced phosphorylation of uterine RIG-I protein in a murine model of pathogenic preterm labor.","authors":"Ayushi Vaidhya, G Ravi Prakash, Dhaval J Kamothi, Ghanshyam Sahu, Laxmi Singh Rathore, Manjit Panigrahi, M Karikalan, Karuna Irungabam, V A Aneesha, Madhu C Lingaraju, Thakur Uttam Singh, Subhashree Parida","doi":"10.1530/REP-24-0299","DOIUrl":"10.1530/REP-24-0299","url":null,"abstract":"<p><strong>In brief: </strong>Preterm labor (PTL) is strongly associated with maternal inflammation, an innate immune response. This study demonstrates that the RIG-I-like receptor (RLR) pathway, a key element of innate immunity, is specifically activated in cases of pathogenic PTL.</p><p><strong>Abstract: </strong>Unlike TLRs, the regulation of RLRs in PTL is not well understood. It is unclear if the RLR pathway is activated in uterine tissue during PTL and whether this activation is specific to pathogenic agents. This study aimed to elucidate the regulation of the RLR pathway in two PTL models. On gestation day 16, PTL was induced in mice using lipopolysaccharide (LPS) for pathogenic inflammation and RU486, a progesterone antagonist, for nonpathogenic inflammation. PTL and fetal viability rates were assessed, and uterine tissue was collected for ELISA, real-time PCR, immunohistochemistry for RIG-I, and Western blot analysis of RIG-I and downstream proteins. Spontaneous and agonist-induced uterine contractility were also evaluated. PTL was induced 8-10 h after LPS and 16-18 h after RU486 administration. Histopathological analysis showed inflammatory changes and neutrophilic infiltration in uterine tissues. Peripheral leukocyte count, TNFα, and IL-6 levels were significantly higher in both LPS- and RU486-treated groups. Agonist-induced uterine contractility was notably reduced in LPS-treated mice. RIG-I mRNA and protein expressions were significantly elevated in LPS-treated animals, with decreased RIG-I phosphorylation, while RU486 treatment did not affect these parameters. IRF3 expression and its phosphorylation demonstrated significant upregulation in both PTL models. In addition, interferon-β and lactate levels were elevated in both groups. The findings suggest that the RLR pathway is activated specifically in the pathogenic model of murine PTL through increased RIG-I expression and decreased phosphorylation.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining core signaling pathways for supporting in vitro maintenance of pig extraembryonic endoderm (XEN) cells.","authors":"Jinsol Jeong, Dong-Kyung Lee, Kwang-Hwan Choi, Dong-Wook Kim, Seokjong Lee, Jong-Nam Oh, Yelim Ahn, Chang-Kyu Lee","doi":"10.1530/REP-24-0393","DOIUrl":"10.1530/REP-24-0393","url":null,"abstract":"<p><p>Extraembryonic endoderm (XEN) cells can be derived from blastocyst primitive endoderm (PrE), becoming a useful tool for studying mammalian development, including early lineage segregation and embryo patterning. Establishment of stem cells representing the respective lineages in blastocysts has been robustly attempted in domestic animals, especially pigs, to reconstitute embryogenesis in vitro for comparative studies. Therefore, we developed a serum-free culture system for pig XEN cells by dissecting the signals governing the core gene network of the PrE lineage. The FGF, LIF and WNT signaling pathways and B27 supplements are essential for maintaining a rapid proliferation rate in pig XEN cells. These cells recapitulated the molecular features and differentiation capacity of the PrE lineage. Especially, the XEN cells incorporated into normal development, retaining cellular identity and contributing to the PrE lineage when injected into in vitro-produced porcine blastocysts. In addition, species-specific characteristics of pigs were observed, including the involvement of lipid metabolism and NANOG/GATA co-expression in XEN cells. Taken together, our findings can contribute to the expansion of the understanding of developmental biology and its biomedical applications by enabling reproducible and homogeneous porcine XEN cell culture.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes to the reproductive microbiome of the brood pouch during male pregnancy in seahorses (Hippocampus abdominalis).","authors":"Jenny Wang, Zoe M G Skalkos, Catherine E Grueber, Camilla M Whittington","doi":"10.1530/REP-24-0159","DOIUrl":"10.1530/REP-24-0159","url":null,"abstract":"<p><strong>In brief: </strong>Reproductive microbiomes contribute to the successful embryogenesis of offspring but are poorly studied in non-mammalian species that exhibit pregnancy. This study characterises the male pregnant seahorse brood pouch microbiome and identifies potential microbial maternal contributions to the pouch, providing insights into the sources and adaptive value of the embryonic microbial environment.</p><p><strong>Abstract: </strong>Seahorses demonstrate an unusual reproductive strategy, in which males incubate embryos inside a complex 'brood pouch' until parturition, analogous to mammalian viviparity. In many species, a 'normal' reproductive microbiome ensures successful embryogenesis and enables parents (usually mothers) to provide their offspring with their initial microbiome. In male-pregnant seahorses, embryos may receive microbiomes from both parents: from the paternal brood pouch and from the maternal eggs. Using the pot-bellied seahorse (Hippocampus abdominalis), we employed 16S rRNA sequencing to explore the reproductive microbiome. We aimed to compare the microbiome of the male pregnant pouch to the male non-pregnant pouch and external skin, and to identify bacterial taxa found exclusively in the pregnant pouch that could be derived maternally from the microbiome of eggs. Our findings demonstrate that the pregnant brood pouch microbiome is compositionally distinct from the non-pregnant pouch and external skin. The pouch microbiome also has characteristics of resistance to colonisation by pathogens, including a low species richness, high species evenness and diversity and very low abundance of Vibrio, a genus that includes fish skin pathogens. Thirteen bacterial taxa appear exclusively in the pregnant pouch, relative to the non-pregnant pouch, and seven of these overlapped with taxa present in or on the eggs. The possible supplementation of brood pouch microbiome with egg-associated micro-organisms hints at a maternal microbial contribution to male pregnancy. This characterisation of the pregnant seahorse pouch microbiome provides a platform for further research into its function and possible adaptive value during male pregnancy.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mammalian heat shock protein A4 family ortholog Hsc70Cb is required for two phases of spermatogenesis in D. melanogaster.","authors":"Brendan J Houston, Joseph Nguyen, Richard Burke, André Nogueira Alves, Gary R Hime, Moira K O'Bryan","doi":"10.1530/REP-24-0458","DOIUrl":"10.1530/REP-24-0458","url":null,"abstract":"<p><strong>In brief: </strong>Hsc70Cb is essential for spermatogonia survival and sperm individualisation in Drosophila. This study highlights the conserved roles of the HSPA4 family across animals and the utility of flies as a model organism for male fertility research.</p><p><strong>Abstract: </strong>Heat shock proteins play essential roles as molecular chaperones, enacting protein folding and preventing protein aggregation. In a previous study, a homozygous non-synonymous genetic variant that was predicted to be damaging was detected in an infertile man in the heat shock protein gene HSPA4L. Here, we used RNA interference in Drosophila melanogaster to explore the role of the heat shock protein A member 4 family (HSPA4) family in male fertility. Expression of the fly orthologue of the mammalian HSPA4 and HSPA4L genes, Hsc70Cb, was reduced in the male germline using two RNAi lines driven by Nanos-Gal4. Robust knockdown of Hsc70Cb in male germ cells resulted in male sterility, characterised by the absence of germ cells in testes and the overproliferation of the testis soma. A less robust knockdown of Hsc70Cb in the male germline resulted in a sperm individualisation defect and a failure of sperm release into the seminal vesicle (analogous to the epididymis). When human HSPA4 or HSPA4L cDNA was introduced into infertile Hsc70Cb mutant flies, a partial rescue was observed, whereby in the robust Hsc70Cb knockdown setting, germ cells progressed to the spermatocyte stage before undergoing cell death. The absence of sperm in Hsc70Cb mutant (line 1) is consistent with the clinical presentation of the infertile man harbouring a homozygous HSPA4L genetic variant, supporting the hypothesis that HSPA4L is required for male fertility in humans and flies. This study also highlights the utility of the fly as a model of human spermatogenesis.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A lack of commensal microbiota influences the male reproductive tract intergenerationally in mice.","authors":"Natalie A Trigg, Simon K Zhou, Jordan C Harris, Madeline N Lamonica, Molly A Nelson, Michael A Silverman, Taku Kambayashi, Colin C Conine","doi":"10.1530/REP-24-0204","DOIUrl":"10.1530/REP-24-0204","url":null,"abstract":"<p><strong>In brief: </strong>Germ-free mice display epididymal transcriptomic changes that were also evident in their conventionalized male offspring and mice lacking T and B cells. This paper demonstrates the role of microbiota and immune cells in the epididymis.</p><p><strong>Abstract: </strong>The microbiome encompasses the array of microorganisms inhabiting various niches in the body and is necessary for numerous physiological processes, including normal metabolism and a functioning immune system. Not only does the absence of a microbiome in mice impact the exposed animals but also inherited phenotypes in successive generations of progeny, suggesting that the absence of a microbiome impacts the germline and gametes. Indeed, recent research has identified a role of the gut microbiome in contributing to male fertility, in both healthy and disease states. While this link is beginning to be established, the impact of the microbiome on the male reproductive tract remains understudied. Here, we utilized a germ-free mouse model to examine the influence of the absence of microbes on the male reproductive tract. In contrast to mice with an established microbiome, germ-free mice display decreased testicular weight and the prevalence of an epididymitis-like inflammation phenotype. These histopathological changes are accompanied by transcriptomic dysregulation in the reproductive tract of germ-free mice, particularly in the cauda epididymis. Moreover, these transcriptomic changes are transmitted to the next generation with high correlation of gene expression in the cauda epididymis between germ-free mice and their conventionalized (microbiome-restored) male offspring, when compared to control mice. Ultimately, our findings identify the reproductive sequalae of males without a functional microbiome and additionally in their conventionalized offspring, suggesting that the paternal microbiota is an underappreciated contributor to male reproductive function.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drosophila AK-3, a homolog of human CKMT1B, is essential for spermiogenesis.","authors":"Meng-Yan Chen, Qian Zhao, Ying-Ying Wang, Yue Ren, Zhi-Xian Cao, Bin Mao, Hao-Lin Wang, Yu-Feng Wang","doi":"10.1530/REP-24-0358","DOIUrl":"10.1530/REP-24-0358","url":null,"abstract":"<p><strong>In brief: </strong>The assembly and maintenance of axonemal microtubules during spermatogenesis is essential for production of functional sperm. This study shows that arginine kinase 3 (AK-3) (human ortholog CKMT1B) is necessary for Drosophila spermiogenesis and its biological function is conserved from flies to humans.</p><p><strong>Abstract: </strong>Spermatogenesis is a conserved process across animals, involving the proliferation and maintenance of germ stem cells, haploid spermatid production via meiosis and the generation of mature sperm with unique shapes. Our previous studies revealed that after ocnus (ocn) knockdown in germlines, the male flies Drosophila melanogaster were sterile, and the expression levels of many proteins were significantly changed. Among these proteins, CG4546 (arginine kinase 3, AK-3) was drastically downregulated, implying its crucial role in fly spermatogenesis. Here, we demonstrate that AK-3 was highly expressed in Drosophila testes. Knockdown of the AK-3 in testes leads to scattered nuclear bundles, loss of the central paired microtubule in the flagellar axoneme, disrupted individualization complexes, lack of mature sperm in seminal vesicles and thus resulting in male complete infertility. Notably, Drosophila AK-3 shares homology with human CKMT1B. Expression of human CKMT1B can rescue the defects in late spermatogenesis and male sterility caused by AK-3 knockdown in flies, indicating that this gene is evolutionarily and functionally conserved. These results suggest that AK-3 contributes to the regulation of spermiogenesis, especially the assembly and stabilizing of the axonemal microtubules during the sperm elongation. These data substantiate the importance of arginine kinase during spermatogenesis and its evolutionary conservation, and might provide fundamental information for studying the function of CKMT1B in male fertility in humans.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uterine stromal but not epithelial PTGS2 is critical for murine pregnancy success.","authors":"Noura Massri, Ripla Arora","doi":"10.1530/REP-24-0408","DOIUrl":"10.1530/REP-24-0408","url":null,"abstract":"<p><p>The use of non-steroidal anti-inflammatory drugs that target prostaglandin synthase (PTGS) enzymes has been implicated in miscarriage. Further, PTGS2-derived prostaglandins are reduced in the endometrium of patients with a history of implantation failure. However, in the mouse model of pregnancy, peri-implantation PTGS2 function is controversial. Some studies suggest that Ptgs2 -/- mice display deficits in ovulation, fertilization and implantation, while other studies suggest a role for PTGS2 only in ovulation but not implantation. Further, the uterine cell type responsible for PTGS2 function and the role of PTGS2 in regulating implantation chamber formation are not known. To address this, we generated tissue-specific deletion models of Ptgs2. We observed that PTGS2 ablation from the epithelium alone in Ltf cre/+ ; Ptgs2 f/f mice and in both the epithelium and endothelium of the Pax2 cre/+ ; Ptgs2 f/f mice does not affect embryo implantation. Further, deletion of PTGS2 in the ovary, oviduct and uterus using Pgr cre/+ ; Ptgs2 f/f does not disrupt pre-implantation events but instead interferes with post-implantation chamber formation, vascular remodeling and decidualization. While all embryos initiate chamber formation, more than half of the embryos fail to transition from blastocyst to epiblast stage, resulting in embryo death and resorbing decidual sites at mid-gestation. Thus, our results suggest no role for uterine epithelial PTGS2 in early pregnancy but instead highlight a role for uterine stromal PTGS2 in modulating post-implantation embryo and implantation chamber growth. Overall, our study provides clarity on the compartment-specific role of PTGS2 and provides a valuable model for further investigating the role of stromal PTGS2 in post-implantation embryo development.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of chronic inflammation on female fertility.","authors":"Stephen Ameho, Michael Klutstein","doi":"10.1530/REP-24-0197","DOIUrl":"10.1530/REP-24-0197","url":null,"abstract":"<p><strong>In brief: </strong>Chronic inflammation causes serious medical conditions in many organs and tissues, including female fertility. Here we review the current literature, showing that chronic inflammation has a negative impact on oocyte quality, folliculogenesis, hormone production, immune signaling and other processes that affect fertility in females.</p><p><strong>Abstract: </strong>Inflammation has key biological roles in the battle against pathogens and additional key processes in development and tissue homeostasis. However, when inflammation becomes chronic, it can become a serious medical concern. Chronic inflammation has been shown to contribute to the etiology and symptoms of serious medical conditions such as ulcerative colitis, cardiovascular diseases, endometriosis and various cancers. One of the less recognized symptoms associated with chronic inflammation is its effect on reproduction, specifically on female fertility. Here we review the current literature, showing that chronic inflammation has a negative impact on oocyte quality, folliculogenesis, hormone production, immune signaling and other processes that affect fertility in females. We discuss several factors involved in the etiology of chronic inflammation and its effect on female fertility. We also discuss possible mechanisms by which these effects may be mediated and how interventions may mitigate the effect of chronic inflammation. Finally, we discuss the notion that in many cases, the effect of chronic inflammation is tightly correlated with and resembles the effect of aging, drawing interesting parallels between these processes, possibly through the effect of aging-associated inflammaging.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11896653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IGF2BP1 stabilizes Akt2 mRNA to promote glucose metabolism and maintain spermatogonial proliferation.","authors":"Yanan Liu, Yuanyuan Chen, Jiahui Fan, Ziqian Min, Xiaowen Liu, Zenghui Mao, Anji Chen, Min Liu, Rong Xia, Lifang Yang, Dan Li","doi":"10.1530/REP-24-0202","DOIUrl":"10.1530/REP-24-0202","url":null,"abstract":"<p><strong>In brief: </strong>The dysregulation of spermatogonial proliferation is one of the causes of male infertility. Using mice as an animal model, this study reveals the function and mechanism of m6A methylation reader insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) and its target Akt2 in spermatogonia.</p><p><strong>Abstract: </strong>IGF2BP1, as a newly identified N6-methyladenosine (m6A) methylation reader, plays a key role in mRNA stability, alternative splicing and translation. However, the function of IGF2BP1 and its target genes in the development of male germ cells remains unclear. In the present study, Western blotting, immunofluorescence and other cellular methods were used to confirm that IGF2BP1 is expressed throughout the male germline with high abundance in spermatogonia of mice, and that its downregulation inhibits spermatogonia proliferation in vitro. Through RNA sequencing, dual luciferase reporter assays, RIP-qPCR and mRNA stability experiments, it was identified that Akt2 is one of the target genes of IGF2BP1. By stabilizing Akt2 mRNA in an m6A-dependent manner, IGF2BP1 maintains spermatogonial proliferation. Furthermore, co-immunoprecipitation and mass spectrometry analyses revealed that PABPC1, DDX5 and FXR1 interact with IGF2BP1, and that the interaction between IGF2BP1 and PABPC1 promotes AKT2 expression. Finally, following the knockdown of both IGF2BP1 and AKT2, glucose and ATP levels in C18-4 and GC-1 spermatogonia cells were found to be reduced, indicating that IGF2BP1 regulates glucose metabolism homeostasis by stabilizing Akt2 expression, thereby influencing spermatogonia proliferation. In addition, analysis of the cryptorchidism database from NCBI revealed that the expression of IGF2BP1 and AKT2 is significantly downregulated in cryptorchid patients with oligospermia or azoospermia. In conclusion, our study elucidates the role and underlying mechanism of IGF2BP1 in spermatogonia, providing a candidate target for male infertility.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potent and sustained enhancement of human sperm motility using novel cyclic AMP upregulators.","authors":"Natalia Oscoz-Susino, Guillermina M Luque, Florencia Minotti, Patricia Otero, Mariano Lavolpe, Mariana Ferrulli, Dario Krapf, Mariano G Buffone, Clara I Marín-Briggiler","doi":"10.1530/REP-24-0448","DOIUrl":"10.1530/REP-24-0448","url":null,"abstract":"<p><strong>In brief: </strong>The cyclic adenosine monophosphate (cAMP) pathway is essential for maintaining sperm physiology. This study examines a cAMP analog and a phosphodiesterase inhibitor that effectively enhance human sperm motility, thereby improving the efficiency of in vitro sperm selection.</p><p><strong>Abstract: </strong>cAMP plays a central role in sperm physiology. Various cAMP upregulators, both cAMP analogs and phosphodiesterase (PDE) inhibitors, have been used in handling human sperm in vitro, although conflicting results and variable responses among patients have been reported. This study aims to evaluate the ability of two compounds - Sp-5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole 3'-5'-cyclic monophosphothioate (cBiMPs), a cAMP analog, and TAK-063, a specific PDE10A inhibitor - to enhance human sperm motility parameters and, consequently, improve sperm preparation procedures. Our results showed that both cBiMPs and TAK-063 significantly enhanced human sperm motility and hyperactivation compared to the control (dimethyl sulphoxide). They also increased protein phosphorylation levels without inducing premature acrosomal exocytosis or DNA fragmentation. The enhancement of sperm motility persisted for 4 h after their removal, surpassing the effects of known cAMP analogs (8-bromo-adenosine-3', 5'-cAMP (8-Br-cAMP) or dibutyryl cAMP (db-cAMP)) or PDE inhibitors (3-isobutyl-1-methylxanthine (IBMX) or pentoxifylline (PTX)). Furthermore, the presence of cBiMPs or TAK-063 during sperm selection resulted in higher recovery rates in comparison to the control, and these compounds effectively improved sperm motion in both fresh and cryopreserved samples with impaired motility. In conclusion, cBiMPs and TAK-063 exhibit potent and sustained effects on human sperm motility, enhancing the efficiency of sperm preparation techniques. The ability to improve sperm motility holds significant implications for male infertility treatment, facilitating the use of low complexity techniques such as intrauterine insemination or in vitro fertilization, and may also aid in selecting viable testicular sperm for intracytoplasmic sperm injection.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}