{"title":"Mind the Gap: A Nationwide Audit of LGBTQ+ Inclusion in Fertility Care Providers in the United Kingdom","authors":"Chloe He, Nour Al-ma'ani, Mei Francis, Jules Sales, Isabella Marson, Neringa Karpavičiūtė, Rishabh Hariharan, Ranya Derrick, Sotirios Saravelos, Luca Sabatini, Sofia Tzouganatou, Devika Nair, Danielle Ellis, Céline Jacques, Timothy Ferrand, Tash Oakes-Monger, Teodora Popa, Francisco Vasconcelos, Cristina Hickman","doi":"10.1530/rep-24-0173","DOIUrl":"https://doi.org/10.1530/rep-24-0173","url":null,"abstract":"<p>LGBTQ+ patients comprise one of the fastest-growing user demographics in fertility care, yet they remain underrepresented in fertility research, practice, and discourse. Existing studies have revealed significant systemic barriers, including cisheteronormativity, discrimination, and gaps in clinical expertise. In this article, we present a checklist of measures clinics can take to improve LGBTQ+ inclusion in fertility care, co-created with members of the LGBTQ+ community. </p><p>This checklist focuses on three key areas: cultural competence, clinical considerations, and online presence. The cultural competence criteria encompass inclusive communication practices, a broad understanding of LGBTQ+ healthcare needs, and knowledge of treatment options suitable for LGBTQ+ individuals. Clinical considerations include awareness of alternative examination and gamete collection techniques for transgender and non-binary patients, the existence of specific clinical pathways for LGBTQ+ patients, and sensitivity to the psychological aspects of fertility care unique to this demographic. The online presence criteria evaluate provider websites for the use of inclusive language and the availability of LGBTQ+-relevant information.\u0000</p><p>The checklist was used as the foundation for an audit of fertility care providers across the UK in early 2024. Our audit identified a widespread lack of LGBTQ+ inclusion, particularly for transgender and non-binary patients, highlighting deficiencies in clinical knowledge and cultural competence. Our work calls attention to the need for further work to understand the barriers to inclusive and competent LGBTQ+ fertility care from both healthcare provider and patient perspectives. </p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":"416 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215204","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}
ReproductionPub Date : 2024-08-27Print Date: 2024-10-01DOI: 10.1530/REP-23-0463
Dongjie Zhou, Xiao-Han Li, Song-Hee Lee, Ji-Dam Kim, Gyu-Hyun Lee, Jae-Min Sim, Xiang-Shun Cui
{"title":"GRK2 is critical for the cleavage of the porcine embryo by regulating HSP90 and the AKT pathway.","authors":"Dongjie Zhou, Xiao-Han Li, Song-Hee Lee, Ji-Dam Kim, Gyu-Hyun Lee, Jae-Min Sim, Xiang-Shun Cui","doi":"10.1530/REP-23-0463","DOIUrl":"10.1530/REP-23-0463","url":null,"abstract":"<p><strong>In brief: </strong>GRK2 deficiency disrupts the early embryonic development in pigs. The regulation of GRK2 on HSP90 and AKT may also play an important role during embryo development and tumor formation.</p><p><strong>Abstract: </strong>Among the family of GPCR kinases (GRKs) that regulate receptor phosphorylation and signaling termination, G-protein-coupled receptor kinase 2 (GRK2) binds to HSP90 in response to hypoxia or other stresses. In this study, we investigated the effects of GRK2 knockdown and inhibition on porcine embryonic development from the zygote stage. Immunofluorescence and western blotting were used to determine the localization and expression, respectively, of GRK2 and related proteins. First, GRK2 and p-GRK2 were expressed in both the cytoplasm and membrane and co-localized with HSP90 on the membrane. The mRNA level of GRK2 increased until the 8C-morula stage, suggesting that GRK2 may play an essential role during the early development of the porcine embryos. GRK2 knockdown reduced porcine embryo development capacity and led to significantly decreased blastocyst quality. In addition, inhibition of GRK2 also induced poor ability of embryo development at an early stage, indicating that GRK2 is critical for embryonic cleavage in pigs. Knockdown and inhibition of GRK2 reduced HSP90 expression, AKT activation, and cAMP levels. Additionally, GRK2 deficiency increased LC3 expression, suggesting enhanced autophagy during embryo development. In summary, we showed that GRK2 binds to HSP90 on the membrane to regulate embryonic cleavage and AKT activation during embryonic development in pigs.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760680","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":"Development of a deep-learning model for detecting positive tubules during sperm recovery for nonobstructive azoospermia.","authors":"Teppei Takeshima, Jurii Karibe, Shinnosuke Kuroda, Yasushi Yumura","doi":"10.1530/REP-24-0181","DOIUrl":"10.1530/REP-24-0181","url":null,"abstract":"<p><p>To enhance surgical testicular sperm retrieval outcome for men with nonobstructive azoospermia, a deep-learning model was developed to identify positive seminiferous tubules by labeling 110 images with sperm-containing tubules sampled during microdissection testicular sperm extraction as training and validation data. After training, the model achieved an average precision of 0.60.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793366","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":"Chromosomal missegregation and aberrant embryo development in repro57 female mice with Rnf212 homozygous mutation.","authors":"Nanami Sono, Mone Takeshita, Mizuho Chikushi, Saki Nakashima, Shoko Miyawaki, Misaki Wakamatsu, Yasuhiro Fujiwara, Tetsuo Kunieda, Junko Otsuki","doi":"10.1530/REP-24-0030","DOIUrl":"10.1530/REP-24-0030","url":null,"abstract":"<p><strong>In brief: </strong>Repro57 mice, bearing an Rnf212 gene mutation, exhibit infertility in both homozygous mutant males and females, revealing arrested spermatogenesis in males and investigating unclear mechanisms in females. The study highlights aneuploidy and altered kinetochore patterns in repro57 homozygous mutant oocytes, which impact later stages of embryo development.</p><p><strong>Abstract: </strong>Repro57 mice, induced with N-ethyl-N-nitrosourea and harboring a mutation in the Rnf212 gene, exhibit infertility in both homozygous mutant males and females. Rnf212 plays a crucial role in recombination and crossover designation. In male repro57 homozygous mutants, spermatocytes often degenerate during late prophase, and mature spermatozoa are absent in the seminiferous epithelium, indicating arrested spermatogenesis as the cause of infertility. Despite reports of infertility in Rnf212-knockout female mice, the specific mechanisms underlying infertility in female repro57 homozygous mutants remain elusive. This study investigates the chromosomal and kinetochore patterns of mature oocytes and their developmental potential following in vitro fertilization in female repro57 homozygous mutant mice. While all wild-type oocytes progress to metaphase II and exhibit euploidy, all repro57 homozygous mutant mouse oocytes display aneuploidy. Additionally, kinetochore distances in repro57 homozygous mutant oocytes exceed those observed in wild-type counterparts. Although no significant differences are noted in fertilization and early embryo development rates between wild-type and repro57 homozygous mutant mice, embryos derived from repro57 homozygous mutants exhibit significantly lower morula and blastocyst rates, accompanied by frequent cytokinesis failure and vacuole formation. These findings suggest that the premature segregation of sister chromatids in repro57 homozygous mutant mice adversely impacts the later stages of embryo development.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752567","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}
ReproductionPub Date : 2024-08-27Print Date: 2024-10-01DOI: 10.1530/REP-24-0049
Edwina F Lawson, Arnab Ghosh, Christopher Grupen, Jacob Netherton, Robert John Aitken, Nathan Druery Smith, Rebecca Lim, Hannah R Drury, Russell Pickford, Zamira Gibb, Mark Baker, Pradeep Singh Tanwar, Aleona Swegen
{"title":"Investigations into the role of platelet-activating factor in the peri-conception period of the mare.","authors":"Edwina F Lawson, Arnab Ghosh, Christopher Grupen, Jacob Netherton, Robert John Aitken, Nathan Druery Smith, Rebecca Lim, Hannah R Drury, Russell Pickford, Zamira Gibb, Mark Baker, Pradeep Singh Tanwar, Aleona Swegen","doi":"10.1530/REP-24-0049","DOIUrl":"10.1530/REP-24-0049","url":null,"abstract":"<p><strong>In brief: </strong>In many mammals, the lipid platelet-activating factor (PAF) has important functions in female reproduction and fertility. This study shows that PAF is present in the reproductive tissues of mares and is involved in processes related to ovulation and early pregnancy.</p><p><strong>Abstract: </strong>Platelet-activating factor (PAF) has been implicated in a number of reproductive processes ranging from ovulation to embryo motility but has not been widely explored in the mare. To identify the presence and examine the role of PAF in the equine periconception processes, targeted mass spectrometry coupled with chromatographic separation was performed on equine follicular fluid (FF), and PAF was quantitatively detected. Subsequently, untargeted high-resolution mass spectrometry-based lipidomic analysis was carried out to quantify PAF in different-sized pre-ovulatory follicles, whereby different molecular species of PAF, PAF (14:0) and PAF (16:1), were both seen to be increasing with follicle diameter. These findings suggest that PAF within FF is increasing as preovulatory follicles approach ovulation. Additionally, immunofluorescence staining identified the PAF receptor in the luminal pericellular, apical, and basal aspect of equine oviductal epithelial cells. Lastly, an equine oviductal epithelial organoid model was generated and showed that the addition of PAF significantly increased the ciliary beat frequency (CBF) (Hz), an action consistent with a role for PAF in embryo migration. It is proposed that the local action of PAF on the ciliated cells of the oviduct propels both the oocyte and the conceptus towards the uterus. In the mare, it appears that PAF is a contributor during the periconception period, potentially being a mediator in the mechanisms of ovulation and in the dialogue of very early pregnancy.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760681","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}
ReproductionPub Date : 2024-08-22Print Date: 2024-09-01DOI: 10.1530/REP-24-0135
Hannah B McDowell, Nathaniel F Henning, Monica M Laronda
{"title":"Heterogeneity of ovarian matrisome hydrogels elucidates factors that may influence follicle growth in vitro.","authors":"Hannah B McDowell, Nathaniel F Henning, Monica M Laronda","doi":"10.1530/REP-24-0135","DOIUrl":"10.1530/REP-24-0135","url":null,"abstract":"<p><p>This work describes a valuable and reproducible method for generating optically clear bovine ovary-derived hydrogels that support in vitro murine follicle growth. These techniques are the foundation in which follicle growth dynamics and matrisome protein composition may be correlated to reveal the influence of matrisome proteins on folliculogenesis.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11341246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141420659","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}
ReproductionPub Date : 2024-08-14Print Date: 2024-09-01DOI: 10.1530/REP-23-0483
Ana Flávia B Silva, Laritza Ferreira Lima, Renata Patrícia Sousa, Renato Félix Silva, Gustavo Cardoso S Neves, Maria Acelina M Carvalho, Anna Clara A Ferreira, Ariclécio Cunha Oliveira, Benner Geraldo Alves, Ana Paula R Rodrigues, Eduardo Leite Gastal, Vilceu Bordignon, José Ricardo Figueiredo
{"title":"Stem cell-conditioned medium improves methylation patterns and quality of caprine preantral follicles.","authors":"Ana Flávia B Silva, Laritza Ferreira Lima, Renata Patrícia Sousa, Renato Félix Silva, Gustavo Cardoso S Neves, Maria Acelina M Carvalho, Anna Clara A Ferreira, Ariclécio Cunha Oliveira, Benner Geraldo Alves, Ana Paula R Rodrigues, Eduardo Leite Gastal, Vilceu Bordignon, José Ricardo Figueiredo","doi":"10.1530/REP-23-0483","DOIUrl":"10.1530/REP-23-0483","url":null,"abstract":"<p><strong>In brief: </strong>Conditioned medium from Wharton's jelly mesenchymal stem cells improved tissue and preantral follicle outcomes, preventing adverse effects of oxidative stress, apoptosis, and epigenetic changes.</p><p><strong>Abstract: </strong>This study investigated the methylation patterns of H3K4me3 and H3K9me3, as well as the mRNA expression of genes encoding the epigenetic regulators KDM1AX1, KDM1AX2, and KDM3A in goat preantral follicles developed in vivo (Uncultured control) or after in vitro culture for 7 days in either the absence (α-MEM+) or presence of conditioned medium (α-MEM+ + CM) from Wharton's jelly mesenchymal stem cells (WJ-MSCs). In the invivo setting, all follicular categories exhibited similar H3K4me3 and H3K9me3 patterns, and transcripts of KDM1AX1, KDM1AX2, and KDM3A were detected in all samples. During in vitro culture, α-MEM+ + CM enhanced several important aspects. It increased the percentage of normal growing follicles, oocyte diameters across all categories, stromal cell density, and the H3K4me3 methylation pattern in preantral follicles. Simultaneously, it decreased the levels of reduced thiols and reactive oxygen species in the spent media, diminished the presence of lipofuscin aggresomes, lowered granulosa cell apoptotic rates, and reduced the H3K9me3 methylation pattern in preantral follicles. In conclusion, the findings from this study provide compelling evidence that supplementing the in vitro culture medium (α-MEM+) with CM from WJ-MSCs has a protective effect on goat preantral follicles. Notably, CM supplementation preserved follicular survival, as evidenced by enhanced follicular and oocyte growth and increased stromal cell density when compared to the standard culture conditions in the α-MEM+ medium. Furthermore, CM reduced oxidative stress and apoptosis and promoted alterations in H3K4me3 and H3K9me3 patterns.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470497","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":"RNA-binding protein SORBS2 increases human trophoblast cell migration via stabilizing HK2 mRNA in preeclampsia.","authors":"Limin Song, Xinying Zhao, Jiaxi Chen, Hang Yin, Hongyan Tang, Lianxiu Li, Haijing Dong, Xinyue Li, Zhihai Qu, Xiaodan Chu, Man Guo","doi":"10.1530/REP-24-0093","DOIUrl":"10.1530/REP-24-0093","url":null,"abstract":"<p><strong>In brief: </strong>SORBS2, an RNA-binding protein, is identified as a regulator of aerobic glycolysis, which is essential for trophoblast migration and placental development. Reduced SORBS2 expression in preeclampsia may impair trophoblast migration by affecting mRNA stability and glycolysis, suggesting its role in the disease's pathogenesis.</p><p><strong>Abstract: </strong>Insufficient trophoblast migration and impaired uterine spiral artery remodeling are implicated in the pathogenesis of preeclampsia, contributing to inadequate placentation. However, the molecular mechanism underlying this process remains unclear. Aerobic glycolysis, which produces substantial lactate, is crucial for establishing a favorable microenvironment for early uterine preparation and supporting embryo implantation and trophoblast migration. In the present study, we have demonstrated that SORBS2, an RNA-binding protein, regulated aerobic glycolysis and significantly improved trophoblast migration in vitro. Our results showed that SORBS2 expression was significantly reduced in human PE placentas and trophoblasts during hypoxia. Overexpression of SORBS2 enhanced cell proliferation and migration, whereas knockdown of SORBS2 decreased these functions in HTR-8/SVneo cells. Mechanistic studies have demonstrated that SORBS2 directly interacts with the 3' untranslated regions (UTRs) of key glycolysis-related genes, specifically HK2. This interaction results in enhanced stability of HK2 and activation of glycolysis. Moreover, silencing HK2 abrogated the enhancement of proliferation and migration of HTR-8/SVneo cells induced by SORBS2. In conclusion, our findings suggest that the downregulation of SORBS2 may contribute to the pathogenesis of preeclampsia by regulating mRNA stability and inhibiting trophoblast migration during placentation.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141601425","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":"Exosomes of mesenchymal stem cells and PRP restore spermatogenesis in the rat model of non-obstructive azoospermia.","authors":"Azar Sheikholeslami, Faezeh Davoodi Asl, Hoda Fazaeli, Mohsen Sheykhhasan, Naser Kalhor, Leila Naserpour","doi":"10.1530/REP-23-0474","DOIUrl":"10.1530/REP-23-0474","url":null,"abstract":"<p><strong>In brief: </strong>Since available therapeutic approaches for chemotherapy-induced non-obstructive azoospermia (NOA) patients are not enough efficient, an urgent need for treatment alternatives is felt. This study shows that adipose tissue-derived mesenchymal stem cells-derived exosome (AD-Exo) treatment is more effective in ameliorating busulfan-induced NOA rat models compared to platelet-rich plasma (PRP).</p><p><strong>Abstract: </strong>Patients with non-obstructive azoospermia (NOA) are unable to have their children. Therefore, there is an urgent need for additional treatment alternatives for these patients. Recently, novel treatments based on the exosomes derived from mesenchymal stem cells (MSCs) as the agents responsible for exerting the paracrine effects and consequently biological functions of MSCs are proposed. Besides, platelet-rich plasma (PRP) as a significant blood byproduct has been therapeutically applied in several male infertility studies. In this study, we compared the effects of PRP and exosome treatment on spermatogenesis restoration in NOA rat models. Exosomes and PRP were isolated from the adipose tissue-derived MSCs (AD-MSCs) collected from conditioned medium and peripheral blood of human volunteers, respectively. Non-obstructive azoospermia (NOA) induction was done through two doses of busulfan at a 21-day interval. Thirty-five days after NOA induction, intratesticular injection of AD-MSCs-derived exosome (AD-Exo), PRP, and PBS was performed. The control group did not receive any treatment. Two months later, the rats were euthanized for further analysis. Our results revealed that both AD-Exo and PRP treatments improved the size and weight of testis, modulated the expression level of Dazl, Ddx4, Stra8, Pwil1, and Ccna1, and ameliorated the serum level of LDH, SOD, and GR enzymes in NOA rats. Moreover, the AD-Exo group showed improved testosterone, GPx, MAD, and CAT serum levels, sperm motility, and protein levels of DAZL and DDX4. This investigation verified the more efficient effects of AD-Exo treatment in comparison to PRP in ameliorating busulfan-induced NOA rat models.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141601424","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}
ReproductionPub Date : 2024-08-08Print Date: 2024-09-01DOI: 10.1530/REP-24-0053
Todd Rosen, Bingbing Wang
{"title":"A proposed model of a clock that governs the length of human pregnancy.","authors":"Todd Rosen, Bingbing Wang","doi":"10.1530/REP-24-0053","DOIUrl":"10.1530/REP-24-0053","url":null,"abstract":"<p><strong>In brief: </strong>The mechanisms that determine the length of pregnancy remain undetermined. Here, we review what has been previously published on the topic and incorporate new data to describe a molecular model in which placental stress and fetal signaling ultimately lead to labor onset in uncomplicated pregnancies.</p><p><strong>Abstract: </strong>The mechanisms that govern the length of human pregnancy have not been determined, while preterm birth remains the leading cause of death and disability in newborns worldwide. Here, we review recent data to generate a novel hypothesis about how the pregnancy clock may function to initiate human labor in uncomplicated pregnancies. In this model, placental stress induced by the growing fetus drives placental production of NFKB, which is then activated by exosomes containing platelet-activating factor and complement 4-binding protein-A from the mature fetus, to drive pro-labor genes in the placenta. A better understanding of the clock that triggers labor may lead to new, more effective therapies to prevent spontaneous preterm birth.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727715","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}