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Extracellular vesicle-encapsulated MiR-25-3p promotes Epithelial-Mesenchymal transition and migration of endometrial epithelial cells by inducing macrophage polarization Mol. Hum. Reprod. (IF 4.0) Pub Date : 2024-02-23 Yue Hu, Ming Yuan, Lei Cheng, Le Xu, Guoyun Wang
The pathogenesis of adenomyosis is closely related to the epithelial-mesenchymal transition and macrophages. MicroRNAs have been extensively investigated in relationship to the epithelial-mesenchymal transition in a range of malignancies. However, there is a paucity of research on extracellular vesicles derived from the eutopic endometrium of adenomyosis and their encapsulated microRNAs. In this study
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The number of nuclei in compacted embryos, assessed by optical coherence microscopy, is a non-invasive and robust marker of mouse embryo quality Mol. Hum. Reprod. (IF 4.0) Pub Date : 2024-02-22 Aleksandra Sobkowiak, Monika Fluks, Ewa Kosyl, Robert Milewski, Marcin Szpila, Szymon Tamborski, Maciej Szkulmowski, Anna Ajduk
Optical coherence microscopy (OCM) visualizes nuclei in live, unlabeled cells. As most cells are uninucleated, the number of nuclei in embryos may serve as a proxy of the cell number, providing important information on developmental status of the embryo. Importantly, no other non-invasive method currently allows for the cell number count in compacted embryos. We addressed the question of whether OCM
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Sperm DNA methylation defects in a new mouse model of the 5,10-methylenetetrahydrofolate reductase 677C>T variant and correction with moderate dose folic acid supplementation Mol. Hum. Reprod. (IF 4.0) Pub Date : 2024-02-17 Edgar Martínez Duncker Rebolledo, Donovan Chan, Karen E Christensen, Alaina M Reagan, Gareth R Howell, Rima Rozen, Jacquetta Trasler
5,10-Methylenetetrahydrofolate reductase (MTHFR) is an enzyme that plays a key role in providing methyl groups for DNA methylation, including during spermatogenesis. A common genetic variant in humans (MTHFR 677C>T) results in reduced enzyme activity and has been linked to various disorders, including male infertility. A new animal model has been created by reproducing the human equivalent of the polymorphism
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O-GlcNAcylation orchestrates porcine oocyte maturation through maintaining mitochondrial dynamics and function Mol. Hum. Reprod. (IF 4.0) Pub Date : 2024-01-24 Wen-Jie Xiong, Xin-Le Lai, Jie Lu, Li-Shu Li, Jin-Xin Zhang, Xing Duan
O-GlcNAc modification exists widely in cells, and the signaling pathways involved in the regulation of important biological processes such as transcription, translation, metabolism and cell cycle. O-GlcNAc modification is an inducible reversible dynamic protein post-translational modification, which regulates complex cellular activities through transient glycosylation and deglycosylation. O-GlcNAc
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Addition of rapamycin or co-culture with cumulus cells from younger reproductive age women does not improve rescue in vitro oocyte maturation or euploidy rates in older reproductive age women Mol. Hum. Reprod. (IF 4.0) Pub Date : 2024-01-05 Marga Esbert, Xin Tao, Agustín Ballesteros, Raziye Melike Yildirim, Richard T Scott, Emre Seli
Both spontaneously conceived pregnancies and those achieved using assisted reproduction decline with advancing maternal age. In this study, we tested if rapamycin and/or cumulus cells (CCs) from young donors could improve oocyte maturation and euploidy rates of germinal vesicle (GV) stage oocytes obtained from older women of reproductive age. A total of 498 GVs from 201 women >38yrs (40.6 ± 1.8, mean
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Endometrial stromal cell autophagy-dependent ferroptosis caused by iron overload in ovarian endometriosis is inhibited by the ATF4-xCT pathway Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-12-19 Xiaoyu Dong, Le Xu, Shuang Wang, Xue Jiao, Shumin Yan, Yufei Huang, Ming Yuan, Guoyun Wang
Ferroptosis is an iron-dependent programmed cell death process characterised by the accumulation of lethal oxidative damage. Localised iron overload is a unique clinical phenomenon in ovarian endometriosis. However, the role and mechanism of ferroptosis in the course of ovarian endometriosis remain unclear. Traditionally, autophagy promotes cell survival. However, a growing body of research suggests
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Human placental vascular and perivascular cell heterogeneity differs between first trimester and term, and in pregnancies affected by fetal growth restriction Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-12-07 Anna L Boss, Lawrence W Chamley, Anna E S Brooks, Joanna L James
Growth-restricted placentae have a reduced vascular network, impairing exchange of nutrients and oxygen. However, little is known about the differentiation events and cell types that underpin normal/abnormal placental vascular formation and function. Here we used 23-colour flow cytometry to characterise placental vascular/perivascular populations between first trimester and term, and in fetal growth
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Aggregated chromosomes/chromatin transfer: a novel approach for mitochondrial replacement with minimal mitochondrial carryover—the implications of mouse experiments for human aggregated chromosome transfer Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-12-01 R Okamoto, W Xiao, H Fukasawa, S Hirata, T Sankai, H Masuyama, J Otsuki
Nuclear transfer techniques, including spindle chromosome complex (SC) transfer and pronuclear (PN) transfer, have been employed to mitigate mitochondrial diseases. Nevertheless, the challenge of mitochondrial DNA (mtDNA) carryover remains unresolved. Previously, we introduced a method for aggregated chromosome (AC) transfer in human subjects, offering a potential solution. However, the subsequent
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GM-CSF improves endometrial receptivity in a thin endometrium rat model by upregulating HOXA10 Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-11-27 Wei Wei, Na Wang, Yanwen Zhu, Maokun Liao, Bian Wang, Tong Du, Jie Zhang, Xiaoyan Mao
Endometrial receptivity is a prerequisite for the success of assisted reproduction., Patients with a consistently thin endometrium frequently fail to conceive, owing to low endometrial receptivity, and there are currently very few therapeutic options available. Our previous study demonstrated that intrauterine granulocyte-macrophage colony-stimulating factor (GM-CSF) administration resulted in a significant
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Advanced maternal age leads to changes within the insulin/IGF system and lipid metabolism in the reproductive tract and preimplantation embryo—insights from the rabbit model Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-11-23 Juliane Trohl, Maria Schindler, Maximilian Buske, Johanna de Nivelle, Alicia Toto Nienguesso, Anne Navarrete Santos
Reproductive potential in women declines with age. The impact of aging on embryo-maternal interactions is still unclear. Rabbits were used as a reproductive model to investigate maternal age-related alterations in reproductive organs and embryos on day 6 of pregnancy. Blood, ovaries, endometrium, and blastocysts from young (16-20 weeks) and advanced maternal age phase (>108 weeks, old) rabbits were
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Intracellular fraction of zona pellucida protein 3 is required for the oocyte-to-embryo transition in mice Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-11-06 Steffen Israel, Julia Seyfarth, Thomas Nolte, Hannes C A Drexler, Georg Fuellen, Michele Boiani
In oocyte biology the zona pellucida has long been known to operate three extracellular functions downstream of the secretory pathway, namely, encasing the oocytes in ovarian follicles, mediating sperm-oocyte interaction and preventing premature embryo contact with oviductal epithelium. The present study uncovers a fourth function that is fundamentally distinct from the other three, being critical
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Human follicular fluid elicits select dose- and age-dependent effects on mouse oocytes and cumulus-oocyte complexes in a heterologous in vitro maturation assay. Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-11-01 Shweta S Dipali,Chanakarn Suebthawinkul,Joanna E Burdette,Mary Ellen Pavone,Francesca E Duncan
Follicular fluid (FF) is a primary microenvironment of the oocyte within an antral follicle. Although several studies have defined the composition of human FF in normal physiology and determined how it is altered in disease states, the direct impacts of human FF on the oocyte are not well understood. The difficulty of obtaining suitable numbers of human oocytes for research makes addressing such a
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Electroacupuncture alleviates intrauterine adhesion through regulating autophagy in rats. Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-11-01 Jingyu Liu,Qian Zhu,Yan Pan,Sainan Hao,Zhaoxian Wang,Chuting Cui,Junwei Li,Yueying Huang,Liangjun Xia,Tiancheng Xu,Jie Cheng,Jie Shen,Youbing Xia
Autophagy is a well-conserved metabolic system that maintains homeostasis by relying on lysosomal breakdown. The endometrium of patients with intrauterine adhesion (IUA) and an animal model exhibits impaired autophagy. Autophagy is negatively correlated with inflammation. Activation of autophagy can inhibit the inflammatory response, while defects in autophagy will activate the inflammatory response
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Hsa_circRNA_BECN1 acts as a ceRNA to promote polycystic ovary syndrome progression by sponging the miR-619-5p/Rab5b axis Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-10-25 Hairui Fan, Dongjie Zhou, Xiaomei Zhang, Min Jiang, Xiang Kong, Tongmin Xue, Lingling Gao, Dan Lu, Chenyue Tao, Liping Wang
Polycystic ovarian syndrome (PCOS) is a common reproductive endocrine disease that affects women of reproductive age. It is also a significant cause of infertility. Circular RNAs (CircRNAs) have been found to have a crucial role in the development and progression of reproductive system diseases. In this study, we focused on circ_BECN1 and aimed to investigate its role and mechanism in PCOS, providing
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Inflammasomes in human reproductive diseases Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-10-03 Yun Chen, Chenyun Miao, Ying Zhao, Liuqing Yang, Ruye Wang, Dan Shen, Ning Ren, Qin Zhang
Inflammasomes are multi-protein complexes localized within immune and non-immune cells that induce caspase activation, proinflammatory cytokine secretion, and ultimately pyroptosis—a type of cell death. Inflammasomes are involved in a variety of human diseases, especially acute or chronic inflammatory diseases. In this review, we focused on the strong correlation between the NLRP3 inflammasome and
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Upregulated TIMP1 facilitates and coordinates myometrial contraction by decreasing collagens and cell adhesive capacity during human labor Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-09-29 Junjie Bao, Xiaodi Wang, Lina Chen, Bolun Wen, Qiu Gao, Xiuyu Pan, Yunshan Chen, Kaiyuan Ji, Huishu Liu
Myometrial contraction is one of the key events involved in parturition. Increasing evidence suggests the importance of the extracellular matrix in this process, in addition to the functional role of myometrial smooth muscle cells, and our previous study identified an upregulated tissue inhibitor of metalloproteinase 1 (TIMP1) in human laboring myometrium compared to nonlabor samples. This study aimed
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Ovarian stimulation with excessive FSH doses causes cumulus cell and oocyte dysfunction in small ovarian reserve heifers Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-09-13 Kaitlin R Karl, Peter Z Schall, Zaramasina L Clark, Meghan L Ruebel, Jose Cibelli, Robert J Tempelman, Keith E Latham, James J Ireland
Excessive FSH doses during ovarian stimulation in the small ovarian reserve heifer (SORH) cause premature cumulus expansion and follicular hyperstimulation dysgenesis (FHD) in nearly all ovulatory-size follicles with predicted disruptions in cell-signaling pathways in cumulus cells and oocytes (before ovulatory hCG stimulation). These observations support the hypothesis that excessive FSH dysregulates
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Treatment with cholesterol just after thawing maintains the fertility of bull sperm Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-08-31 Mazharul Md Islam, Takashi Umehara, Natsumi Tsujita, Masanori Koyago, Masayuki Shimada
Freezing and thawing diminish sperm motility and fertility by disrupting the cholesterol balance in sperm plasma and organelle membranes. The aim of this study was to elucidate the mechanisms through which cholesterol enhances the quality of frozen-thawed bull sperm. The incorporation of cholesterol was investigated using boron-dipyrromethene (BODIPY)-cholesterol, and BODIPY signals were detected not
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'Human and Animal Model Reproductive Epigenetics' special collection: (un)intended marks on fertility. Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-08-30 Michele Boiani,Francesca E Duncan
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Maternal age and gonadotrophin elevation cooperatively decrease viable ovulated oocytes and increase ootoxicity, chromosome-, and spindle-misalignments: “2-Hit” and “FSH-OoToxicity” mechanisms as new reproductive aging hypotheses Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-08-28 Lori R Bernstein, Amelia C L Mackenzie, Keith Durkin, Duane C Kraemer, Charles L Chaffin, Istvan Merchenthaler
While there is consensus that advanced maternal age (AMA) reduces oocyte yield and quality, the notion that high FSH reduces oocyte quality and causes aneuploidy remains controversial, perhaps due to difficulties controlling the confounding variables of age and FSH levels. Here, contributions of age and gonadotrophin elevation were separately controlled using a mouse model of human female reproductive
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TRPV2, a novel player in the human ovary and human granulosa cells Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-08-22 Katja Eubler, Karolina M Caban, Gregory A Dissen, Ulrike Berg, Dieter Berg, Carola Herrmann, Nicole Kreitmair, Astrid Tiefenbacher, Thomas Fröhlich, Artur Mayerhofer
The cation channel ‘transient receptor potential vanilloid 2’ (TRPV2) is activated by a broad spectrum of stimuli, including mechanical stretch, endogenous and exogenous chemical compounds, hormones, growth factors, reactive oxygen species and cannabinoids. TRPV2 is known to be involved in inflammatory and immunological processes, which are also of relevance in the ovary. Yet neither the presence nor
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Control of mitochondrial integrity influences oocyte quality during reproductive aging Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-08-18 Shaihla A Khan, Laura Reed, William B Schoolcraft, Ye Yuan, Rebecca L Krisher
Reduced quality in oocytes from women of advanced maternal age is associated with dysfunctional mitochondria. The objective of this study was to investigate the mechanisms controlling mitochondrial quality during maternal aging in mouse and human oocytes. We first evaluated the expression of proteins involved in the mitochondrial unfolded protein response (UPRmt) and mitophagy in in-vivo matured metaphase
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CircKDM5B sponges miR-128 to regulate porcine blastocyst development by modulating trophectoderm barrier function Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-07-20 Di Gao, Xin Wang, Ye-Lian Yan, Chao Li, Yong-Peng Tan, Qiu-Chen Liu, Meng-Ya Zhang, Jian V Zhang, Qing-Yuan Sun, Zu-Bing Cao, Yun-Hai Zhang
Circular RNAs (circRNAs), which exert critical functions in the regulation of transcriptional and posttranscriptional gene expression, are found in mammalian cells but their functions in mammalian preimplantation embryo development remain poorly understood. Here, we showed that circKDM5B mediated miRNA128 to regulate porcine early embryo development. We screened circRNAs potentially expressed in porcine
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Extravillous trophoblast cell derived exosomes induce vascular smooth muscle cell apoptosis via a mechanism associated with miR-143-3p Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-06-27 Hanbo Liu, Miaojuan Chen, Fen Ning, Yixin Ye, Qinsheng Lu, Shenjiao Lu, Yaoyun Duan, Xiaowen Gan, Mingguang Zhao, Kaimin Guo, Gendie E Lash
The remodeling of uterine spiral arteries is a complex process requiring the dynamic action of various cell types. During early pregnancy, extravillous trophoblast cells (EVT) differentiate and invade the vascular wall, replacing the vascular smooth muscle cells (VSMCs). Several in vitro studies have shown that EVT cells play an important role in promoting VSMC apoptosis, however the mechanism underlying
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Return of the forgotten hero: the role of Y chromosome-encoded Zfy in male reproduction Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-06-24 Hayden Holmlund, Yasuhiro Yamauchi, Victor A Ruthig, Julie Cocquet, Monika A Ward
The Y-linked zinc finger gene ZFY is conserved across eutherians and known to be a critical fertility factor in some species. The initial studies of the mouse homologues, Zfy1 and Zfy2, were performed using mice with spontaneous Y chromosome mutations and Zfy transgenes. These studies revealed that Zfy is involved in multiple processes during spermatogenesis, including removal of germ cells with unpaired
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Genetic variants underlying developmental arrests in human preimplantation embryos Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-06-19 Saffet Ozturk
Developmental arrest in preimplantation embryos is one of the major causes of assisted reproduction failure. It is briefly defined as a delay or a failure of embryonic development in producing viable embryos during ART cycles. Permanent or partial developmental arrest can be observed in the human embryos from 1-cell to blastocyst stages. These arrests mainly arise from different molecular biological
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Safety of multiple administrations of spermicidal LL-37 antimicrobial peptide into the mouse female reproductive tract Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-06-16 Seung Gee Lee, Wongsakorn Kiattiburut, Stephanie C Burke Schinkel, Jonathan Angel, Nongnuj Tanphaichitr
We have previously demonstrated spermicidal activity of LL-37 antimicrobial peptide on mouse/human sperm and its contraceptive effects in female mice. With its microbicidal action against Neisseria gonorrhoeae, LL-37 warrants development into a multipurpose prevention technology (MPT) agent for administering into the female reproductive tract (FRT). However, it is important to verify that multiple
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Genome-wide analysis of histone modifications that underlie the dynamic changes in gene expression during decidualization in human endometrial stromal cells Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-06-13 Isao Tamura, Amon Shiroshita, Taishi Fujimura, Yumiko Tanaka-Doi, Yuichiro Shirafuta, Ryo Maekawa, Toshiaki Taketani, Shun Sato, Norihiro Sugino
Human endometrial stromal cells (hESCs) undergo a differentiation process with dramatic changes in cell functions during the menstrual cycle, which is called decidualization. This is an important event for implantation of the embryo and successful pregnancy. Defective decidualization can cause implantation failure, miscarriage, and unexplained infertility. A number of genes are up-regulated or down-regulated
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Progesterone signaling in regulation of luteal steroidogenesis Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-06-08 Kayhan Yakin, Francesko Hela, Ozgur Oktem
The corpus luteum is the major source of progesterone, the essential hormone for female reproductive function. While progesterone activity has been the subject of extensive research for decades, characterization of noncanonical progesterone receptor/signaling pathways provided a new perspective for understanding the complex signal transduction mechanisms exploited by the progesterone hormone. Deciphering
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Specific processing of meiosis-related transcript is linked to final maturation in human oocytes Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-05-31 Sara Pietroforte, Montserrat Barragan Monasterio, Anna Ferrer-Vaquer, Manuel Irimia, Elena Ibáñez, Mina Popovic, Rita Vassena, Filippo Zambelli
Human meiosis in oocytes entails an intricate regulation of the transcriptome to support late oocyte growth and early embryo development, both crucial to reproductive success. Currently, little is known about the co- and post-transcriptional mRNA processing mechanisms regulating the last meiotic phases, which contribute to transcriptome complexity and influence translation rates. We analyzed gene expression
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Systematic assessment of hexavalent chromium-induced damage to male fertility and the preventive role of melatonin: a longitudinal study from the translational point of view Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-05-26 Tianjiao Li, Yinghua Lv, Zhili Wu, Ming Guo, Ruifang Liu, Wenxian Zeng, Yi Zheng
Chromium (Cr) and its compounds are closely associated with individuals’ lives and extensively used in industry. Excessive exposure to hexavalent chromium (Cr (VI)) induces oxidative damage of various organs including the testes, posing a serious threat to male reproductive fitness. As an endogenous antioxidant, melatonin holds potent antioxidative and anti-inflammatory properties, becoming a potential
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Loss-of-function mutations in IQCN cause male infertility in humans and mice owing to total fertilization failure. Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-06-30 Yulin Wang,Guoyong Chen,Zhenzhen Tang,Xiaoyan Mei,Chunli Lin,Jingyi Kang,Jianqing Lian,Jun Lu,Yun Liu,Fenghua Lan,Wujian Huang,Duo Zhang
Fertilization failure is a significant manifestation of unexplained male infertility. Previous work has suggested a genetic origin. In this study, we report on a man with unexplained infertility from a large consanguineous marriage family. Whole-exome sequencing and Sanger sequencing identified a homozygous frameshift variation of the IQ motif containing N (IQCN; GenBank: NM_001145304.1; c.1061_1062delAT;
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Androgen signalling in the ovaries and endometrium Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-05-12 Abbey C Lissaman, Jane E Girling, Lynsey M Cree, Rebecca E Campbell, Anna P Ponnampalam
Currently, our understanding of hormonal regulation within the female reproductive system is largely based on our knowledge of estrogen and progesterone signalling. However, while the important functions of androgens in male physiology are well known, it is also recognised that androgens play critical roles in the female reproductive system. Further, androgen signalling is altered in a variety of gynaecological
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Cyclic processes in the uterine tubes, endometrium, myometrium, and cervix: pathways and perturbations. Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-04-29 Sarah J Holdsworth-Carson,Ellen Menkhorst,Jacqueline A Maybin,Anna King,Jane E Girling
This review leads the 2023 Call for Papers in MHR: 'Cyclical function of the female reproductive tract' and will outline the complex and fascinating changes that take place in the reproductive tract during the menstrual cycle. We will also explore associated reproductive tract abnormalities that impact or are impacted by the menstrual cycle. Between menarche and menopause, women and people who menstruate
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Call for papers: cyclical function of the female reproductive tract. Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-04-29 Michele Boiani,Francesca E Duncan
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SKF96365 modulates activity of CatSper channels in human sperm Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-04-27 Elis Torrezan-Nitao, Sean Brown, Linda Lefievre, Jennifer Morris, Joao Correia, Claire Harper, Stephen Publicover
Exposure of human sperm to progesterone (P4) activates cation channel of sperm (CatSper) channels, inducing an intracellular Ca2+ concentration ([Ca2+]i) transient followed by repetitive [Ca2+]i activity (oscillations), which are believed to be functionally important. We investigated the potential significance of store-operated Ca2+-entry in these oscillations using the inhibitor SKF96365 (30 µM; SKF)
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Escherichia coli inhibits endometriosis by inducing M1 polarity of peritoneal macrophages and the IL-1 signaling pathway Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-04-20 S M Yan, Y F Huang, L Xu, X Y Dong, S Wang, X Jiao, M Yuan, G Y Wang
The development of endometriosis is closely linked to macrophages, and the type M1 macrophage has been hypothesized to play an inhibitory role in its progression. Escherichia coli induces macrophage polarization toward M1 in numerous diseases and differs in the reproductive tract of patients with and without endometriosis; however, its specific role in endometriosis development remains unknown. Therefore
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A long-acting recombinant FSH supports high-quality mouse follicle development and oocyte maturation in vitro by co-ordinating somatic and germ cell transcriptomes Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-04-17 Shao-Yuan Liu, Yan-Chu Li, Xin-Yi Tian, Yong Zhou, Kang-Ping Guo, Heng-Yu Fan, Xing-Wei Liang, Xiang-Hong Ou, Qian-Qian Sha
Strategies to maximize individual fertility chances are constant requirements of ART In vitro folliculogenesis may represent a valid option to create a large source of immature ovarian follicles in ART. Efforts are being made to set up mammalian follicle culture protocols with suitable FSH stimuli. In this study, a new type of recombinant FSH (KN015) with a prolonged half-life is proposed as an alternative
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Functional analysis of rare anti-Müllerian hormone protein-altering variants identified in women with PCOS Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-04-02 L Meng, A McLuskey, A Dunaif, J A Visser
Recently rare heterozygous AMH protein-altering variants were identified in women with PCOS, causing reduced anti-Müllerian hormone (AMH) signaling. However, the exact functional mechanism remains unknown. Here, we analyzed the processing, secretion and signaling of these AMH variants. Functional analysis of six PCOS-specific AMH variants (V12G, P151S, P270S, P352S, P362S, H506Q) and one control-specific
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Semaphorin 4C regulates ovarian steroidogenesis through RHOA/ROCK1-mediated actin cytoskeleton rearrangement Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-03-09 Dan Chen, Chuqing Wu, Simin Wei, Yican Guo, Meng Wu, Su Zhou, Fangfang Fu, Weicheng Tang, Liru Xue, Jinjin Zhang, Yan Li, Jun Dai, Yuanyuan Li, Shuangmei Ye, Shixuan Wang
Semaphorins are a family of evolutionarily conserved morphogenetic molecules that were initially found to be associated with axonal guidance. Semaphorin 4C (Sema4C), a member of the fourth subfamily of semaphorins, has been demonstrated to play multifaceted and important roles in organ development, immune regulation, tumour growth and metastasis. However, it is completely unknown whether Sema4C is
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Dynamics of extracellular vesicle-coupled microRNAs in equine follicular fluid associated with follicle selection and ovulation. Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-04-03 Samuel Gebremedhn,Ahmed Gad,Ghassan M Ishak,Nico G Menjivar,Melba O Gastal,Jean M Feugang,Radek Prochazka,Dawit Tesfaye,Eduardo L Gastal
Innumerable similarities in reproductive cyclicity and hormonal alterations highlight the considerable utility of the mare to study aspects of follicular dynamics and reproductive function in view of the largely constricted, human research subjects. The bi-directional communication between the growing oocyte and the surrounding somatic cells embodies the hallmark of mammalian follicular development
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Basolateral secretions of human endometrial epithelial organoids impact stromal cell decidualization Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-02-23 Harriet C Fitzgerald, Andrew M Kelleher, Chaman Ranjit, Danny J Schust, Thomas E Spencer
Uterine glands and, by inference, their secretions impact uterine receptivity, blastocyst implantation, stromal cell decidualization, and placental development. Changes in gland function across the menstrual cycle are primarily governed by the steroid hormones estrogen (E2) and progesterone (P4) but can also be influenced by extrinsic factors from the stroma. Using a human endometrial epithelial organoid
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MALDI mass spectrometry imaging shows a gradual change in the proteome landscape during mouse ovarian folliculogenesis Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-02-02 Giulia Fiorentino, Andrew Smith, Giovanna Nicora, Riccardo Bellazzi, Fulvio Magni, Silvia Garagna, Maurizio Zuccotti
Our knowledge regarding the role proteins play in the mutual relationship among oocytes, surrounding follicle cells, stroma, and the vascular network inside the ovary is still poor and obtaining insights into this context would significantly aid our understanding of folliculogenesis. Here, we describe a spatial proteomics approach to characterise the proteome of individual follicles at different growth
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Testis-Specific Actin-Like 7A (ACTL7A) is an indispensable protein for subacrosomal associated F-actin formation, acrosomal anchoring, and male fertility Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-02-02 P Ferrer, S Upadhyay, M Ikawa, T M Clement
Formation of the acrosome during spermiogenesis is an essential process for creating fertilization competent sperm. Of the numerous aspects required for acrosome biogenesis, adherence of the acrosomal outer membrane to the nuclear surface is mediated by the subacrosomal perinuclear theca. However, the cellular dynamics and congruent functions pertaining to these acrosomal anchoring factors are not
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Multiomics Approach to Profiling Sertoli Cell Maturation during Development of the Spermatogonial Stem Cell Niche Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-01-23 A L Voigt, R Dardari, N L M Lara, T He, H Steele, A Dufour, K E Orwig, I Dobrinski
Spermatogonial stem cells (SSCs) are the basis of spermatogenesis, a complex process supported by a specialized microenvironment, called the SSC niche. Postnatal development of SSCs is characterized by distinct metabolic transitions from prepubertal to adult stages. An understanding of the niche factors that regulate these maturational events is critical for the clinical application of SSCs in fertility
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Men who inject opioids exhibit altered tRNA-Gly-GCC isoforms in semen Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-01-19 Germán Gornalusse, Ryan M Spengler, Erin Sandford, Yeseul Kim, Claire Levy, Muneesh Tewari, Florian Hladik, Lucia Vojtech
In addition to their role in protein translation, tRNAs can be cleaved into shorter, biologically active fragments called tRFs. Specific tRFs from spermatocytes can propagate metabolic disorders in second generations of mice. Thus, tRFs in germline cells are a mechanism of epigenetic inheritance. It has also been shown that stress and toxins can cause alterations in tRF patterns. We were therefore
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Preconception Paternal Alcohol Exposure Decreases IVF Embryo Survival and Pregnancy Success Rates in a Mouse Model Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-01-12 Alexis N Roach, Katherine N Zimmel, Kara N Thomas, Alison Basel, Sanat S Bhadsavle, Michael C Golding
Increasingly, couples struggling with fertility turn to assisted reproductive techniques, including in vitro fertilization (IVF), to have children. Despite the demonstrated influence of periconception male health and lifestyle choices on offspring development, studies examining IVF success rates and child health outcomes remain exclusively focused on maternal factors. Using a physiologically relevant
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Comprehensive molecular analysis identifies eight novel variants in XY females with disorders of sex development Mol. Hum. Reprod. (IF 4.0) Pub Date : 2023-01-05 Vinayak Kulkarni, Selvaa Kumar Chellasamy, Somprakash Dhangar, Jagdish Ghatanatti, Babu Rao Vundinti
Disorders of sex development (DSD) are a group of clinical conditions with variable presentation and genetic background. Females with or without development of secondary sexual characters and presenting with primary amenorrhea (PA) and a 46, XY karyotype are one of the classified groups in DSD. In this study, we aimed to determine the genetic mutations in 25 females with PA and a 46, XY karyotype to
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Pre-implantation mouse embryo movement under hormonally altered conditions Mol. Hum. Reprod. (IF 4.0) Pub Date : 2022-12-28 Hannah Lufkin, Diana Flores, Zachary Raider, Manoj Madhavan, Madeline Dawson, Anna Coronel, Dhruv Sharma, Ripla Arora
Pre-implantation embryo movement is crucial to pregnancy success, but the role of ovarian hormones in modulating embryo movement is not understood. We ascertain the effects of altered hormonal environment on embryo location using two delayed implantation mouse models: natural lactational diapause (ND); and artificially induced diapause (AD), a laboratory version of ND generated by ovary removal and
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WDR87 interacts with CFAP47 protein in the middle piece of spermatozoa flagella to participate in sperm tail assembly Mol. Hum. Reprod. (IF 4.0) Pub Date : 2022-12-26 Hong-Qing Liao, Zi-Yi Guo, Li-Hua Huang, Gang Liu, Jin-Feng Lu, Yun-Fei Zhang, Xiao-Wei Xing
Spermatogenesis is a complex process that includes spermatogonia self-renewal, spermatocyte meiosis and spermatozoa assembly. Recent studies have revealed that WD40-repeat domain-containing (WDR) proteins play important roles in spermatocyte division, spermatozoa flagella assembly and head shaping. In this study, we investigated the expression pattern of WDR87 and found that it was highly expressed
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In vivo promotion of primordial follicle activation by stem cell factor treatment in mice with premature ovarian insufficiency and advanced age Mol. Hum. Reprod. (IF 4.0) Pub Date : 2022-12-07 Yibo Wang, Jiawei Zhang, Jing Liang, Longzhong Jia, Shudong Niu, Kaixin Cheng, Chen Yang, Zining Lu, Lu Mu, Xuebing Yang, Yan Zhang, Hua Zhang
Dormant primordial follicles (PFs) are the most abundant reproductive resource in mammalian ovaries. With advances in the mechanism of study of the regulation of PF activation, PFs have been used to improve fertility in clinical practice. As a central controlling element of follicle activation signaling, the pre-granulosa cell-secreted stem cell factor (SCF; also known as KIT ligand, KITL), which initiates
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Segmental aneuploid hotspots identified across the genomeconcordant on re-analysis Mol. Hum. Reprod. (IF 4.0) Pub Date : 2022-12-02 Keelee J McCarty, Mary E Haywood, Rachel Lee, Lauren Henry, Alison Arnold, Susanna McReynolds, Blair McCallie, Bill Schoolcraft, Mandy Katz-Jaffe
The aim of this study was to characterize a large set of full segmental aneuploidies identified in trophectoderm (TE) biopsies and evaluate concordance in human blastocysts. Full segmental aneuploid errors were identified in TE biopsies (n=2,766) from preimplantation genetic testing for aneuploid (PGT-A) cycles. Full segmental deletions (n=1,872; 66.1%) presented twice as many times as duplications
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Senescent endometrial stromal cells transmit reactive oxygen species to the trophoblast-like cells and impair spreading of blastocyst-like spheroids Mol. Hum. Reprod. (IF 4.0) Pub Date : 2022-11-12 P I Deryabin, J S Ivanova, A V Borodkina
Successful implantation requires a fine-tuned dialog between the invading embryo and the maternal endometrium. Recently we discovered that premature senescence of endometrial stromal cells (EnSC) might mediate improper decidual transformation of endometrial tissue and impair endometrial-blastocyst interaction. Here we show that senescent EnSC are characterized by elevated intracellular reactive oxygen
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Host defense functions of the epididymal amyloid matrix Mol. Hum. Reprod. (IF 4.0) Pub Date : 2022-11-09 Caitlyn Myers, Mary Catherine Hastert, Gail A Cornwall
The epididymal lumen is an immunologically distinct environment. It maintains tolerance for the naturally antigenic spermatozoa to allow their maturation into functional cells while simultaneously defending against pathogens that can ascend the male tract and cause infertility. We previously demonstrated that a nonpathological amyloid matrix that includes several CRES (cystatin-related epididymal spermatogenic)
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Metabolic and secretory recovery of slow frozen-thawed human ovarian tissue in vitro Mol. Hum. Reprod. (IF 4.0) Pub Date : 2022-11-04 Rebekka Einenkel, Andreas Schallmoser, Nicole Sänger
Within the options available for fertility preservation, cryopreservation of ovarian cortical tissue has become an important technique. Freezing and thawing procedures have been optimized to preserve tissue integrity and viability. However, the improvement of the tissue retransplantation is currently of great interest. Rapid angiogenesis is needed at the retransplantation site to accomplish sufficient
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Mitochondrial aggregation caused by cytochalasin B compromises the efficiency and safety of three-parent embryo Mol. Hum. Reprod. (IF 4.0) Pub Date : 2022-10-18 Ying Li, Sanbao Shi, Jin Yuan, Xi Xiao, Dongmei Ji, Jianxin Pan, Zhunyuan Min, Hao Wang, Hongying Sha, Yazhong Ji
It is widely accepted that cytochalasin B (CB) is required in enucleation of the oocyte in order to stabilize the cytoplasm. However, CB treatment results in the uneven distribution of mitochondria, with aggregation towards the nucleus, which might compromise the efficiency and safety of a three-parent embryo. Here, we demonstrated that CB treatment affected mitochondrial dynamics, spindle morphology
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Predicted COVID-19 molecular effects on endometrium reveal key dysregulated genes and functions Mol. Hum. Reprod. (IF 4.0) Pub Date : 2022-10-07 I Henarejos-Castillo, A Devesa-Peiro, L de Miguel-Gomez, P Sebastian-Leon, M Romeu, A Aleman, C Molina-Gil, A Pellicer, I Cervello, P Diaz-Gimeno
COVID-19 exerts systemic effects that can compromise various organs and systems. Although retrospective and in-silico studies and prospective preliminary analysis have assessed the possibility of direct infection of the endometrium, there is a lack of in-depth and prospective studies on the impact of systemic disease on key endometrial genes and functions across the menstrual cycle and window of implantation
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Progesterone suppresses podocalyxin partly by up-regulating miR-145 and miR-199 in human endometrial epithelial cells to enhance receptivity in in-vitro models Mol. Hum. Reprod. (IF 4.0) Pub Date : 2022-09-16 Manizha Shekibi, Sophea Heng, Yao Wang, Nirukshi Samarajeewa, Luk Rombauts, Guiying Nie
Establishment of endometrial surface receptivity is crucial for the initiation of embryo implantation, yet the molecular mechanisms are not well understood especially in the human. We have recently discovered that podocalyxin (PODXL) is a critical negative regulator of human endometrial surface receptivity. PODXL is highly expressed in all epithelial and endothelial cells in the non-receptive endometrium
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Follicle isolation methods reveal plasticity of granulosa cell steroidogenic capacity during mouse in vitro follicle growth Mol. Hum. Reprod. (IF 4.0) Pub Date : 2022-09-07 Elnur Babayev, Min Xu, Lonnie D Shea, Teresa K Woodruff, Francesca E Duncan
Follicles are the functional unit of the ovary and several methods have been developed to grow follicles ex vivo, which recapitulate key events of oogenesis and folliculogenesis. Enzymatic digestion protocols are often used to increase the yield of follicles from the ovary. However, the impact of these protocols on the outermost theca and granulosa cells, and thereby follicle function, is not well
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Inhibition of YAP/TAZ-TEAD activity induces cytotrophoblast differentiation into syncytiotrophoblast in human trophoblast Mol. Hum. Reprod. (IF 4.0) Pub Date : 2022-08-22 Tetsuya Mizutani, Makoto Orisaka, Yumiko Miyazaki, Ririko Morichika, Miki Uesaka, Kaoru Miyamoto, Yoshio Yoshida
During placentation, placental cytotrophoblast (CT) cells differentiate into syncytiotrophoblast (ST) cells and extravillous trophoblast (EVT) cells. In the placenta, the expression of various genes is regulated by the Hippo pathway through a transcription complex, Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ)-TEA domain transcription factor (TEAD) (YAP/TAZ-TEAD)