Reproduction最新文献

{"title":"Dimethyloxaloylglycine-preconditioned Human Umbilical Cord Mesenchymal Stem Cells Protects Against Early Pregnancy Loss in Mice.","authors":"Anfeng Ning, Nansong Xiao, Xiaoqin Yu, Hu Wang, Chunyi Guan, Xu Ma, Hong-Fei Xia","doi":"10.1530/REP-24-0285","DOIUrl":"10.1530/REP-24-0285","url":null,"abstract":"<p><p>Early pregnancy loss (EPL), a common pregnancy complication, yet has few effective preventive measures currently. To investigate whether dimethyloxaloylglycine (DMOG)-preconditioned human umbilical cord mesenchymal stem cells (hUC-MSCs) can prevent EPL, we initially evaluated the effect of DMOG on hUC-MSCs in vitro. Subsequently, the DMOG-preconditioned hUC-MSCs were transplanted into the lipopolysaccharide (LPS)-induced murine abortion model for intervention, following which we conducted phenotypic analysis. It was found that DMOG treatment enhanced the mRNA expression of Hif1α, H19, and Glut1 in hUC-MSCs and augmented their migration capability (P < 0.01). Co-culture experiments showed that DMOG-treated hUC-MSCs notably reduced the mRNA levels of Il6, Il1b, and Tnfa in LPS-induced HTR-8/SVneo cells (P < 0.01). Moreover, DMOG-preconditioned hUC-MSCs remarkably decreased the fetal resorption rate and increased the embryo weight in LPS-induced abortive mice (P < 0.01). Histological analysis indicated that DMOG-preconditioned hUC-MSCs more effectively promoted their homing and inhibited LPS-induced fibrosis at the maternal-fetal interface. Apart from suppressing inflammatory factors in the serum of pregnant mice, DMOG-preconditioned hUC-MSCs can downregulate the mRNA levels of Il2, Il1b, Tnfa, Il5, and Il9 (P < 0.01), which are pro-inflammatory cytokines secreted by M1 macrophages; and simultaneously upregulate the expression of Cd206 and Pparg (P < 0.01), which serve as the cell surface and nuclear receptors of M2 macrophages, in the embryos. Immunofluorescence further verified that the transplantation of DMOG-preconditioned hUC-MSCs could increase the expression of CD206 in embryos. Therefore, DMOG-preconditioned hUC-MSCs might prevent EPL by promoting the transformation of M1 into M2 macrophages.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796233","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":"Impact of intraamniotic inflammation on tryptophan metabolism in the placenta-fetal brain axis in rats.","authors":"Cilia Abad, Ivana Musilova, Eva Cifkova, Ramon Portillo, Fiona Kumnova, Rona Karahoda, Martin Sterba, Miroslav Lisa, Marian Kacerovsky, Jaroslav Stranik, Ales Stuchlik, František Štaud","doi":"10.1530/REP-24-0378","DOIUrl":"10.1530/REP-24-0378","url":null,"abstract":"<p><p>The placenta plays a crucial role beyond nutrient transfer, acting as a dynamic endocrine organ that significantly influences maternal physiology and fetal development. It responds rapidly to even slight changes in the in utero environment to promote fetal survival. Disruptions in placental function are increasingly recognized as key contributors to the origins of neurodevelopmental disorders. In this study, we employed advanced technology to induce intrauterine inflammation through ultrasound-guided administration of LPS into gestational sacs. We then evaluated its effects on the gene expression of enzymes involved in TRP metabolism and conducted a comprehensive LC/MS analysis of the metabolome in the placenta and fetal brain of Wistar rats. Our results show that intraamniotic injection of LPS induces a robust inflammatory response leading to significant alterations in TRP metabolism, including downregulation of tryptophan hydroxylase (TPH) in the placenta, resulting in a decrease in serotonin (5-HT) levels. Similarly, in the fetal brain, exposure to LPS led to reduced TPH expression and increased monoamine oxidase expression, suggesting a decrease in 5-HT synthesis and an increase in its degradation. Furthermore, an upregulation of the kynurenine pathway was observed in both the placenta and fetal brain. Moreover, we detected a shift towards neurotoxicity, evidenced by an imbalance between neuroprotective and neurotoxic metabolites, including decreased levels of kynurenic acid and upregulation of kynurenine monooxygenase in the fetal brain. In conclusion, our findings reveal significant alterations in TRP metabolism following intrauterine inflammation, potentially contributing to neurodevelopmental disorders.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796239","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":"Histomorphometry and Sperm Quality in Male Rats Exposed to 2.45 GHz Wi-Fi.","authors":"Sivasatyan Vijay, Siti Fatimah Ibrahim, Khairul Osman, Aini Farzana Zulkefli, Mohd Farisyam Mat Ros, Norazurashima Jamaludin, Syed Muhamad Asyraf Syed Taha, Atikah Hairulazam, Farah Hanan Fathihah Jaffar","doi":"10.1530/REP-25-0048","DOIUrl":"10.1530/REP-25-0048","url":null,"abstract":"<p><p>Numerous studies have documented the effect of 2.45GHz Wi-Fi exposure on the testes and sperm quality. Nevertheless, detailed histological alterations of other male reproductive organs are underexplored. Therefore, this study aimed to evaluate detailed histological alterations of the testes, epididymis, seminal vesicle, coagulating organ, and sperms parameters following 2.45GHz Wi-Fi exposure. Eighteen adult male Sprague Dawley rats (N=18) were equally divided into three groups (n=6): Control, 4-hour, and 24-hour groups. The groups were exposed to an active router daily for 4 or 24 hours, respectively. The Control group was sham-exposed using an inactive router. The exposure lasted for eight weeks at a 20cm distance, with a power density of 0.141W/m² and a specific absorption rate (SAR) of 0.41W/Kg. Histological findings revealed vacuolation in the testes and the corpus epididymis of the 4-hour and 24-hour groups. The seminal vesicle in both exposed groups exhibited multifocal atypical hyperplasia. Besides, the seminiferous tubule diameter decreased gradually in both exposed groups, with a substantial decrease in the 24-hour group. The spermatogenesis index in 4-hour and 24-hour groups also reduced significantly. The latter result was reflected in the sperm concentration, where both groups showed a significant reduction compared to the Control group. Sperm motility also decreased significantly in the 4-hour groups. Interestingly, there was a substantial increase in sperm viability in the 24-hour group. These findings indicate that 2.45GHz Wi-Fi exposure causes changes in the histology and histomorphometry measurement and impairs important sperm parameters. This highlights the consequences following Wi-Fi exposure on male reproductive health.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796236","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":"Irisin decreases follicle development in cattle and inhibits theca cell steroidogenesis through focal adhesion kinase signaling.","authors":"Mathilde Daudon, Christelle Ramé, Marcos H Barreta, Alfredo Q Antoniazzi, Valério M Portela, Europa Meza-Serrano, Joëlle Dupont, Christopher A Price","doi":"10.1530/REP-24-0352","DOIUrl":"10.1530/REP-24-0352","url":null,"abstract":"<p><strong>In brief: </strong>Irisin is a muscle and adipose-derived hormone that is secreted in response to negative energy balance in cattle. We show here that irisin reduced follicle growth and theca cell function.</p><p><strong>Abstract: </strong>At the onset of lactation, dairy cattle are anestrous owing mainly to a state of negative energy balance. Adipose tissue is mobilized to meet the energy demands of milk production, and this alters the secretion of adipose-derived hormones, called adipokines. Irisin is a myokine/adipokine that may play a role in fertility; plasma concentrations increase in cattle postpartum, and irisin decreased progesterone and estradiol secretion from bovine granulosa cells in vitro. To our knowledge, the effects of irisin on bovine theca cell function in vitro and on follicle growth in vivo have not been reported. We hypothesized that irisin negatively affects theca cell function in vitro and causes follicle regression in vivo using well-established bovine models. Under physiological concentrations of insulin (0.2 ng/mL), irisin did not affect glucose uptake, but decreased testosterone secretion and stimulated PTK2 and MTOR phosphorylation. Inhibiting PTK2 activity abolished the ability of irisin to decrease testosterone secretion. Injection of irisin directly into a growing follicle in vivo caused follicle regression. We conclude that irisin decreases bovine theca cell steroidogenesis through PTK2 signaling, and combined effects on theca and granulosa cells cause follicle regression.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586437","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":"Nicotinamide riboside supplementation protects against maternally diabetes-associated decline in oocyte quality.","authors":"Chenlu Wei, Xinxin Zeng, Keer Wang, Mengchen Wang, Min Lei, Zhenye Zhu, Yining Xu, Yanqing Zhao, Qingling Yang, Ying-Pu Sun","doi":"10.1530/REP-24-0350","DOIUrl":"10.1530/REP-24-0350","url":null,"abstract":"<p><p>Diabetes mellitus is strongly correlated with a decline in oocyte quality, however, non-invasive and effective methods to improve this issue have yet to be fully development. Here, we demonstrate that in vivo supplementation with nicotinamide riboside (NR) 400 mg/kg/day for 14 days effectively enhances the quality of oocytes from diabetic mice induced by streptozocin 190 mg/kg by restoring nicotinamide adenine dinucleotide (NAD+) levels. NR supplementation not only improved superovulation function of diabetic mice but also improved their oocyte quality and embryonic development potential after fertilization by maintaining normal spindle structure and alleviating mitochondrial dysfunction. In addition, NR supplementation reduced ROS levels in oocytes rom diabetic mice. Overall, our findings suggest that dietary NR supplementation is a viable strategy to protect oocytes from diabetes-related deterioration, thereby enhancing reproductive outcomes in maternal diabetes and improving the efficacy of assisted reproductive technology.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664395","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":"Meiotic arrest, resumption, and TZP retraction in bovine COCs undergoing pre-IVM: lessons from a refined GV stage classification.","authors":"Helena Fabiana Reis de Almeida Saraiva, Juliano Rodrigues Sangalli, Luana Alves, Juliano Coelho da Silveira, Flávio Vieira Meirelles, Felipe Perecin","doi":"10.1530/REP-23-0235","DOIUrl":"10.1530/REP-23-0235","url":null,"abstract":"<p><p>The nuclear, cytoplasmic, and molecular maturation of the mammalian oocyte is a finely orchestrated sequence of events that relies on proper cumulus-oocyte communication. Bovine oocytes enter the in vitro maturation systems at the germinal vesicle stage (GV) exhibiting four different chromatin configurations (GV0-GV3). Herein, we associate the oocyte chromatin and nuclear lamina configurations to propose a refined GV classification (GV0, GV1.1-GV1.3, GV2.1-GV2.3, and GV3.1-GV3.3). This refined GV classification system was correlated with oocyte meiosis resumption and transzonal projections (TZPs) density of COCs submitted to three IVM systems (control IVM; and a modified IVM preceded or not by a pre-IVM step). Pre-IVM resulted in lower polar body extrusion rates at 19 h IVM, albeit ~24% of the oocytes extruded their first polar body at 9 h IVM. Pre-IVM sustained 80% of oocytes meiotically arrested but altered GV distribution, reducing GV2 and increasing GV1.3 and GV3.3 categories. Pre-IVM reduced TZP densities predominantly in pre-matured GV3 and GVBD COCs. At 9 h of IVM, both groups matured in modified IVM showed lower TZP densities compared to immature and IVM control. Gene expression supports the TZP density differences, with ERK2 and PRKACA upregulation in pre-matured cumulus and in modified IVM groups at 9 h of IVM. GDF9 and BMP15 levels were similar between treated and control groups at all time points. Our findings indicate that despite the IVM system, the initial oocyte GV stage influences pre-IVM and IVM outcomes. The refined GV classification system is a useful tool to oocyte biologists.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731340","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":"Increased plugging latency in cycling epiERα -/- (Esr1 f/- Wnt7a Cre/+ ) mice.","authors":"Jonathan Matthew Hancock, Taylor Elijah Martin, Zidao Wang, Jackson Kyle Sundgren, Xiaoqin Ye","doi":"10.1530/REP-24-0447","DOIUrl":"10.1530/REP-24-0447","url":null,"abstract":"<p><p>Wnt7a-Cre is a commonly used driver for generating uterine epithelial conditional knockout mice, such as epiERα -/- (Esr1 f/- Wnt7a Cre/+ ) and epiPR -/- (Pgr f/- Wnt7a Cre/+ ). We noticed that epiERα -/- females, but not epiPR -/- females, have prolonged plugging latency, which is the duration between continuous cohabitation and detection of the first vaginal plug (a sign of mating). Mating occurs in proestrus and/or estrus stages of the estrous cycle. Vaginal cytology detected estrous cyclicity in all mice examined, although epiERα -/- mice had leukocyte-dominant vaginal cytology throughout the estrous cycle and their estrous cyclicity appeared less regular. Estrous cyclicity and mating activity are regulated by the hypothalamic-pituitary-ovarian axis, in which kisspeptin plays essential roles. ERα and PR are expressed in the rostral periventricular area of the ventricle (RP3V) and arcuate nucleus (ARC) kisspeptin neurons in the hypothalamus. It has been reported that Esr1 f/f Kiss1-Cre mice lack estrous cyclicity, while Pgr f/f Kiss1-Cre mice have normal estrous cyclicity at two months old, and Wnt7a is highly expressed in ARC. The prolonged plugging latency in epiERα -/- mice could be contributed by the deletion of ERα in Wnt7a-positive cells in ARC. Wnt7a-Cre was also used to generate uterine epithelial RhoA-deficient mice, epiRhoA -/- (RhoA f/- Wnt7a Cre/+ ). However, both female and male RhoA f/- Wnt7a Cre/+ mice had hydrocephalus and died within a few weeks of age. Our observations of increased plugging latency in epiERα -/- mice and hydrocephalus in RhoA f/- Wnt7a Cre/+ mice exemplify unintended neuronal gene deletion using Wnt7a-Cre for uterine epithelial-specific gene deletion.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11859491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047442","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":"CD40 ligand and CD40: expression, regulation and function at the maternal-conceptus interface in pigs.","authors":"Inkyu Yoo, Soohyung Lee, Yugyeong Cheon, Tae Sub Park, Hakhyun Ka","doi":"10.1530/REP-24-0396","DOIUrl":"10.1530/REP-24-0396","url":null,"abstract":"<p><strong>In brief: </strong>The CD40 ligand-CD40 signaling system expressed at the maternal-conceptus interface in pigs is involved in regulating maternal immunity by modifying endometrial endothelial cell function during early pregnancy. This paper reveals the role of CD40 ligand-CD40 signaling at the maternal-conceptus interface in pigs.</p><p><strong>Abstract: </strong>To successfully establish and maintain pregnancy in pigs, a variety of factors must work together at the maternal-conceptus interface to form an immune environment appropriate for both the mother and the conceptus. Our transcriptomics study has shown that cluster of differentiation ligand 40 (CD40L) and its receptor CD40, which are known to play important roles in regulating cell- and antibody-mediated immunity, are expressed in the endometrium during early pregnancy. However, the roles of the CD40L and CD40 signaling system are not well understood. Therefore, we determined the expression, regulation and function of CD40L and CD40 at the maternal-conceptus interface in pigs. The endometrium expressed CD40L and CD40 mRNAs at the greatest levels on day 15 of pregnancy. The CD40L protein was localized predominantly to luminal epithelial cells on day 15 of pregnancy, and the CD40 protein was found in luminal epithelial, stromal and vascular endothelial cells in the endometrium during pregnancy. During early pregnancy, the conceptus expressed CD40 but not CD40L and chorioallantoic tissues during mid- to late pregnancy expressed both CD40L and CD40. Interferon-γ increased the expression of CD40L and CD40 in endometrial explants. CD40L increased the migration but not the proliferation of cultured porcine uterine endothelial (pENDO) cells in vitro. In addition, CD40L affected the expression of genes related to angiogenesis, cell adhesion, chemokines and immunity in pENDO cells. These results suggest that the CD40L-CD40 system might play an important role in the establishment of pregnancy in pigs by regulating endometrial endothelial cell function during the implantation period.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060457","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":"Loss of PRICKLE1 leads to subfertility, aberrant extracellular matrix and abnormal myometrial architecture in mice.","authors":"Emily R Roberts, Sornakala Ganeshkumar, Sumedha Gunewardena, Vargheese Chennathukuzhi","doi":"10.1530/REP-24-0344","DOIUrl":"10.1530/REP-24-0344","url":null,"abstract":"<p><strong>In brief: </strong>PRICKLE1, a WNT/planar cell polarity (PCP) protein that is downregulated in uterine leiomyoma, plays an important role in myometrial tissue architecture and extracellular matrix (ECM) deposition. This paper shows that myometrial-specific ablation of the mouse Prickle1 gene results in a uterine leiomyoma phenotype.</p><p><strong>Abstract: </strong>Uterine leiomyomas (ULs) are the most prevalent benign tumors of the female reproductive tract, originating from the myometrium and affecting over 75% of reproductive-age women. Symptoms of UL include pelvic pain, pressure, dysmenorrhea, menorrhagia, anemia and reproductive dysfunction. Currently, there is no effective long-term pharmacotherapy for UL, making them the leading cause of hysterectomies in the United States. The lack of treatment options is attributed to the absence of accurate animal models and a limited understanding of UL pathogenesis. Previous research has shown that the loss of repressor of element 1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) within the myometrium promotes UL pathogenesis. In addition, deletion of Rest in the mouse myometrium leads to a UL phenotype. PRICKLE1, also known as Rest-interacting LIM-domain protein (RILP), is required for nuclear localization of REST and Wnt/PCP signaling, making it a critical target for UL studies. In the context of PCP, smooth muscle cells in UL show abnormal organization, aberrant ECM structure and expression levels, potentially influenced by PRICKLE1 loss. The exact role of PRICKLE1 and Wnt/PCP in UL pathogenesis remains unclear. To explore PRICKLE1's role in UL, we deleted Prickle1 using our myometrial-specific iCre. Our findings demonstrate that Prickle1 loss in the myometrium results in a UL phenotype characterized by altered collagen expression, excessive ECM deposition, aberrant smooth muscle cell organization, increased Esr1 and Pgr expression and dysregulated Wnt/PCP signaling. This novel mouse model serves as a valuable preclinical tool for understanding UL pathogenesis and developing future pharmacotherapies.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829680","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}