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Jacob R. Maxon J Maxon, Neuroscience Program, University of Illinois System, Urbana, United States

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Megan M. Mahoney M Mahoney, Comparative biosciences, University of Illinois System, Urbana, 61802, United States

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Sexual reproduction—from both physiological and behavioral perspectives—is dependent upon appropriate connections between a diverse, hormone-modulated network of neural regions. Importantly, these substrates are regulated by hormones across the lifespan from early development to adulthood, making them targets of endocrine-disrupting chemicals (EDCs). Rodents, such as mice and rats, are invaluable to the characterization of EDCs because of their sex-specific, stereotyped appetitive and consummatory reproductive behaviors. Phthalates, bisphenol A (BPA), and EDC mixtures pose a salient risk to the health of humans, wildlife, and livestock because these synthetic compounds are ubiquitous due to their widespread use in mass production of consumer and industrial goods. This review outlines how the hypothalamic-pituitary-gonadal axis regulates male and female sexual behaviors, and how phthalates and BPA can perturb appetitive and consummatory behaviors and impact neural substrates that modulate reproductive behavior. We will then discuss how to progress toward a clearer understanding of the reproductive and neurobiological changes that occur due to EDC exposure.

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Aileen F. Keating A Keating, Animal Science, Iowa State University of Science and Technology, Ames, United States

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Jason W Ross J Ross, Animal Science, Iowa State University of Science and Technology, Ames, United States

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Lance Baumgard L Baumgard, Animal Science, Iowa State University of Science and Technology, Ames, United States

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Heat stress (HS) in mammals results from an imbalance in heat accumulation and dissipation. Fertility impairments consequential to HS have been recognized for decades in production animals, and more recently, observations have been extended to other species including women. There are several systemic impacts of HS that can independently affect reproduction including metabolic endotoxemia, reduced plane of nutrition and endocrine disruption. At the level of the ovary, molecular pathways are altered by HS such as inflammation, JAK-STAT, PI3K, oxidative stress, cell death and heat shock response. Taken together, impaired ovarian function contributes to seasonal infertility that results from HS. This review paper describes physiological and endocrine systemic impacts of HS that may independently and collaboratively impair fertility in the porcine model. The review then details ovarian intracellular events that are altered during HS and finally determine futures needs in this area of research.

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Azar Sheikholeslami Department of Mesenchymal Stem Cells, Academic Center for Education, Culture, and Research (ACECR), Qom Branch, Qom, Iran

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Faezeh Davoodi Asl Department of Mesenchymal Stem Cells, Academic Center for Education, Culture, and Research (ACECR), Qom Branch, Qom, Iran

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Hoda Fazaeli Department of Mesenchymal Stem Cells, Academic Center for Education, Culture, and Research (ACECR), Qom Branch, Qom, Iran

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Mohsen Sheykhhasan Department of Mesenchymal Stem Cells, Academic Center for Education, Culture, and Research (ACECR), Qom Branch, Qom, Iran

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Naser Kalhor Department of Mesenchymal Stem Cells, Academic Center for Education, Culture, and Research (ACECR), Qom Branch, Qom, Iran

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Leila Naserpour Department of Reproductive Biology, Academic Center for Education, Culture, and Research (ACECR), Qom Branch, Qom, Iran

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In brief

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).

Abstract

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.

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Min Zhang College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an City, P. R. China

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Jia-Shun Wu College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an City, P. R. China

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Xiao Han College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an City, P. R. China

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Rui-Jie Ma College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an City, P. R. China

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Jia-Li Xu College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an City, P. R. China

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Ming-Tao Xu College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an City, P. R. China

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Hong-Jie Yuan College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an City, P. R. China

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Ming-Jiu Luo College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an City, P. R. China

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Jing-He Tan College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an City, P. R. China

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In brief

Genes expressed in cumulus cells might be used as markers for competent oocytes/embryos. This study identified and validated a new group of cumulus expansion and/or apoptosis-regulating genes, which may be used for selection of quality oocytes/embryos.

Abstract

Studies on the mechanisms behind cumulus expansion and cumulus cell (CC) apoptosis are essential for understanding the mechanisms for oocyte maturation. Genes expressed in CCs might be used as markers for competent oocytes and/or embryos. In this study, both in vitro (IVT) and in vivo (IVO) mouse oocyte models with significant difference in cumulus expansion and CC apoptosis were used to identify and validate new genes regulating cumulus expansion and CC apoptosis of mouse oocytes. We first performed mRNA sequencing and bioinformatic analysis using the IVT oocyte model to identify candidate genes. We then analyzed functions of the candidate genes by RNAi or gene overexpression to select the candidate cumulus expansion and CC apoptosis-regulating genes. Finally, we validated the cumulus expansion and CC apoptosis-regulating genes using the IVO oocyte model. The results showed that while Spp1, Sdc1, Ldlr, Ezr and Mmp2 promoted, Bmp2, Angpt2, Edn1, Itgb8, Cxcl10 and Agt inhibited cumulus expansion. Furthermore, Spp1, Sdc1 and Ldlr inhibited CC apoptosis. In conclusion, by using both IVT and IVO oocyte models, we have identified and validated a new group of cumulus expansion and/or apoptosis-regulating genes, which may be used for selection of quality oocytes/embryos and for elucidating the molecular mechanisms behind oocyte maturation.

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Wen Zheng Laboratory of Clinical Proteomics and Metabolomics, Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, PR China
Metabolomics and Proteomics Technology Platform, West China Hospital, Sichuan University, Chengdu, PR China

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Liang Zhang Chengdu Research Base of Giant Panda Breeding, Chengdu, PR China

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Kailai Cai Chengdu Research Base of Giant Panda Breeding, Chengdu, PR China

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Kongju Wu Chengdu Research Base of Giant Panda Breeding, Chengdu, PR China

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Ge Liang Metabolomics and Proteomics Technology Platform, West China Hospital, Sichuan University, Chengdu, PR China

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Lu Zhang Metabolomics and Proteomics Technology Platform, West China Hospital, Sichuan University, Chengdu, PR China

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Lihui Liao Chengdu Research Base of Giant Panda Breeding, Chengdu, PR China

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Fujun Shen Chengdu Research Base of Giant Panda Breeding, Chengdu, PR China

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Wenping Zhang Chengdu Research Base of Giant Panda Breeding, Chengdu, PR China

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Li Wang Chengdu Research Base of Giant Panda Breeding, Chengdu, PR China

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Yan Li Chengdu Research Base of Giant Panda Breeding, Chengdu, PR China

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Ye Wang Chengdu Research Base of Giant Panda Breeding, Chengdu, PR China

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Jie Kou Chengdu Research Base of Giant Panda Breeding, Chengdu, PR China

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Yi Zhong Metabolomics and Proteomics Technology Platform, West China Hospital, Sichuan University, Chengdu, PR China

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Xin Li Laboratory of Clinical Proteomics and Metabolomics, Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, PR China

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Jingqiu Cheng Laboratory of Clinical Proteomics and Metabolomics, Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, PR China

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Meng Gong Laboratory of Clinical Proteomics and Metabolomics, Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, PR China

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Rong Hou Chengdu Research Base of Giant Panda Breeding, Chengdu, PR China

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In brief

The metabolic processes of the gestation period in pandas remain poorly understood. Our study comprehensively characterizes the metabolism of giant pandas during gestation and proposes arginine and histidine as potential novel biomarkers for detecting the pregnancy state of giant pandas.

Abstract

There has been remarkable progress in the conservation and reproduction of giant pandas. However, the physiology of the gestation period in pandas remains poorly understood. The metabolic processes from estrus to pregnancy are dynamic and precisely regulated, playing a crucial role in pregnancy and related dysfunctions. In this study, we conducted a metabolomic analysis of 37 blood samples collected from pandas in estrus, acyclic, and potential pregnant states, employing rigorous screening to minimize the influence of diet. Our findings suggest that a reduced appetite can serve as an indicator for evaluating implantation time, representing a characteristic response to pregnancy and aiding in the prediction of delivery time in pregnant pandas. Metabolomic results indicate great metabolism variation from estrus to pregnancy, highlighting the association between amino acid metabolism and pregnancy outcomes. Compared to other pandas, individuals who successfully bred exhibit significantly elevated levels of arginine and histidine, even 2 months before experiencing a reduced appetite. Furthermore, the lipid profile undergoes distinct dynamic changes only in estrus samples. In summary, our study comprehensively characterizes the metabolism of giant pandas during gestation and proposes arginine and histidine as potential novel biomarkers for detecting the pregnancy state of giant pandas.

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Chatchanan Ausavarungnirun C Ausavarungnirun, Department of pathology and Laboratory Medicine, University of Chicago NorthShore, Chicago, United States

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Kyle E. Orwig K Orwig, University of Pittsburgh School of Medicine, Ob/Gyn and Reproductive Sciences, Pittsburgh, United States

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Transgender individuals who pursue alignment with their gender identity, through medical treatments or surgery face challenges to family building because the medical community lacks the understanding or infrastructure to serve the reproductive needs of transgender or non-binary people. Fertility preservation (FP) offers a crucial opportunity for the transgender community, enabling individuals to exercise autonomy over their reproductive choices. While fertility preservation has been extensively studied in other populations such as cancer patients, the unique biology and clinical care of the transgender and gender non-binarydiverse (TGD) individuals has challenged direct translation of what can be offered for cisgender individuals. Additionally, the FP services in transgender communities are reportedly under-utilized, despite the prevalent desire of TGD individuals to have children. This review aims to provide up-to-date information on the current standard of care and experimental FP options available to TGD individuals and their potential reproductive outcomes. We will also discuss the barriers to the success of FP utilization, from both the biology/medical aspect and the perspectives of TGD population. By recognizing the unique family building challenges faced by TGD people and potential areas of improvement, appropriate adjustments can be made to better support fertility preservation in the TGD community.

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Hannah B McDowell Department of Pediatrics, Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

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Nathaniel F Henning Departments of Chemistry and Molecular Biosciences, Northwestern University, Evanston, Illinois, USA

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Monica M Laronda Department of Pediatrics, Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
Stanley Manne Children’s Research Institute, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois, USA
Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

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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.

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Eva Held-Hoelker Institute of Animal Sciences, Animal Breeding and Husbandry group, Rheinische Friedrich-Wilhelms-Universitat Bonn, Endenicher Allee, Bonn, Germany
Department of Animal Science, Biotechnology and Reproduction of Farm Animals, Georg-August-University Goettingen, Burckhardtweg, Göttingen, Germany.

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Jessica Kurzella Institute of Animal Sciences, Animal Breeding and Husbandry group, Rheinische Friedrich-Wilhelms-Universitat Bonn, Endenicher Allee, Bonn, Germany

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Dessie Salilew-Wondim Institute of Animal Sciences, Animal Breeding and Husbandry group, Rheinische Friedrich-Wilhelms-Universitat Bonn, Endenicher Allee, Bonn, Germany
Department of Animal Science, Biotechnology and Reproduction of Farm Animals, Georg-August-University Goettingen, Burckhardtweg, Göttingen, Germany.

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Franca Rings Institute of Animal Sciences, Animal Breeding and Husbandry group, Rheinische Friedrich-Wilhelms-Universitat Bonn, Endenicher Allee, Bonn, Germany

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Dawit Tesfaye Department of Biomedical Sciences, Animal Reproduction and Biotechnology Laboratory, Colorado State University, Fort Collins, USA

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Ernst Tholen Institute of Animal Sciences, Animal Breeding and Husbandry group, Rheinische Friedrich-Wilhelms-Universitat Bonn, Endenicher Allee, Bonn, Germany

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Christine Grosse-Brinkhaus Institute of Animal Sciences, Animal Breeding and Husbandry group, Rheinische Friedrich-Wilhelms-Universitat Bonn, Endenicher Allee, Bonn, Germany

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Michael Hoelker Department of Animal Science, Biotechnology and Reproduction of Farm Animals, Georg-August-University Goettingen, Burckhardtweg, Göttingen, Germany.

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In brief

In the present study the sustainable effect of L-carnitine during the culture period on the post-transfer development was investigated. Taken together, we uncovered direct effects of L-carnitine on the bioenergetic profile of day 7 blastocysts along with sustainable effects on mtDNA copy numbers and transcriptome profile of bovine day 14 embryos.

Abstract

L-Carnitine (LC) is known to play key roles in lipid metabolism and antioxidative activity, implicating enhanced cryotolerance of bovine blastocysts. However, sustainability of LC supplementation during culture period on preimplantation development beyond the blastocyst stage has not been investigated so far. Therefore, all embryos were cultured under fatty acid-free conditions, one group with LC (LC embryos) and the control group without LC (control) supplementation. Transfer to recipients was conducted on day 6. Elongation-stage embryos were recovered on day 14; metrics of embryo recollection, developmental rates as regards early elongation-stage as well as mean embryo length did not differ between the groups. Gene expression analyses via NGS revealed 341 genes to be differentially regulated between elongation-stage embryos derived from LC supplementation compared to controls. These played mainly a role in molecular functions and biological processes like oxidoreductase activity, ATP-dependent activity, cellular stress, and respiration. Pathways like oxidative phosphorylation and thermogenesis, extracellular matrix receptor signaling, PI3K-Akt, and focal adhesion were affected by differentially regulated genes. Moreover, all DEGs located on the mitochondria were significantly downregulated in LC embryos, being in line with lower mitochondrial copy number and mtDNA integrity compared to the control group. Finally, we uncovered alterations of the bioenergetic profile on day 7 as a consequence of LC supplementation for the first time, revealing significantly higher oxygen consumption rates, ATP linked respiration and spare capacity for LC embryos. In summary, we uncovered direct effects of LC supplementation during the culture period on the bioenergetic profile along with sustainable effects on mtDNA copy numbers and transcriptome profile of bovine day 14 embryos.

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Wenqian Xiong Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

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Jie Jin Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Department of Obstetrics and Gynecology, Guangzhou Women and Children’s Medical Center, Guangzhou, China

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Yi Liu Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

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In brief

Failure to induce mesenchymal–epithelial transition (MET) during stromal cell decidualization can lead to consequences such as impaired fertility in patients with endometriosis. METTL3-mediated m6A modification plays an important role in attenuating MET and defective decidualization of endometrial stromal cells and contributes to the development of reduced endometrial receptivity in endometriosis.

Abstract

Mesenchymal–epithelial transition (MET)-mediated endometrial decidualization is pivotal for achieving endometrial receptivity and successful pregnancy. We observed blockade of MET in the eutopic secretory endometrium of patients with endometriosis, but the underlying mechanism is unknown. In this study, real-time PCR was used to detect PRL and IGFBP1 expression, whereas western blotting was used to detect the expression of MET markers and METTL3. Phalloidin staining was used to identify changes in cell morphology. M6A levels were quantified using a colorimetric method and m6A dot blots, and functional analysis was performed using spheroid adhesion assays. We first found that increased E-cadherin expression was accompanied by decreased vimentin and Slug expression in the eutopic secretory endometrium of individuals with endometriosis. We also detected a significant increase in both the m6A level and the expression of the related methyltransferase METTL3. Finally, METTL3 expression was negatively correlated with PRL, IGFBP1, and MET markers expression. Collectively, our findings suggest that METTL3 mediates m6A modification, thereby inhibiting MET formation within the eutopic secretory endometrium of patients with endometriosis. Increased METTL3-mediated m6A modification plays a crucial role in attenuating MET formation and decidualization impairment in endometrial stromal cells, ultimately contributing to compromised endometrial receptivity in individuals with endometriosis. These insights could lead to the identification of potential therapeutic targets for improving both endometrial receptivity and pregnancy rate among individuals affected by endometriosis.

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Todd Rosen Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA

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Bingbing Wang Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA

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In Brief

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.

Abstract

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.

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