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Molecular Human Reproduction

Xin Yin, Rufei Gao, Yanqing Geng, Xuemei Chen, Xueqing Liu, Xinyi Mu, Yubin Ding, Yingxiong Wang, Junlin He
Folate deficiency has been linked to a wide range of pregnancydisorders. Most researchabout folate-deficiency has focused on the embryo itself, little attention has been paid to possible effects on theplacenta. According to our results, themorphology of the placenta, endocrine function and the expression of genes involved in placental differentiation were all abnormal in folated-deficient mice on days 10, 12 and 14 of pregnancy. Similar results were found in human placenta explants cultured in folate-deficient medium...
April 11, 2019: Molecular Human Reproduction
Q N Nguyen, N Zerafa, S H Liew, J K Findlay, M Hickey, K J Hutt
It is well established that DNA-damaging chemotherapies can cause infertility and ovarian endocrine failure by depleting the ovarian reserve of primordial follicles. Currently, no effective pharmacological therapies exist for the preservation of long-term fertility and ovarian function in female cancer patients, due to a limited understanding of the mechanisms of chemotherapy-induced follicle depletion. This study investigated the cellular targets, molecular mechanisms, and temporal course of ovarian reserve depletion following treatment with commonly used chemotherapeutic drugs...
April 6, 2019: Molecular Human Reproduction
Qian Zhou, Yan Lian, Yan Zhang, Lei Li, Hongyan Li, Di Shen, Yu Zhou, Meihua Zhang, Yuan Lu, Jing Liu, Yu Xia, X T Wang
Platelet-derived microparticles (PMPs) are a type of microparticle budding from platelets undergoing activation or apoptosis in many autoimmune diseases, including antiphospholipid antibody syndrome (APS). PMPs may also contribute to recurrent recurrent miscarriage, although the exact mechanism is unclear. The aim of this study was to determine the potential biological mechanism by which abnormal PMP activation may affect recurrent miscarriage. PMPs were counted by fluorescence-activated cell sorting (FACS) and compared between the healthy control (HC) and recurrent miscarriage/APS groups...
April 3, 2019: Molecular Human Reproduction
L C Morley, D J Beech, J J Walker, Simpson Nab
Blood flow, and the force it generates, is critical to placental development and function throughout pregnancy. This mechanical stimulation of cells by the friction generated from flow is called shear stress (SS) and is a fundamental determinant of vascular homeostasis, regulating remodelling and vasomotor tone. This review describes how SS is fundamental to the establishment and regulation of the blood flow through the uteroplacental and fetoplacental circulations. Amongst the most recent findings is that alongside the endothelium, embryonic stem cells and the villous trophoblast are mechanically sensitive...
April 1, 2019: Molecular Human Reproduction
Yao Tang, Hongjin Ji, Haiyan Liu, Jing Liu, Weirong Gu, Ting Peng, Xiaotian Li
Preterm labour is a common pregnancy complication contributing to major maternal and fetal morbidity and mortality. We have found microRNA (miR)-212-3p, a potential infection-associated molecule, was significantly over-expressed during human preterm labour. However, the mechanism remains unknown. In this study, we have adopted a lipopolysaccharide (LPS)-induced Institute of Cancer Research murine preterm model to examine the role of miR-212-3p in the infection-induced preterm labour. Myometrial miR-212-3p expression was increased by nearly 4-fold in the term labour group (P = 0...
March 20, 2019: Molecular Human Reproduction
Desiree Lucia Fend-Guella, Kathrein von Kopylow, Andrej-Nikolai Spiess, Wolfgang Schulze, Andrea Salzbrunn, Stefan Diederich, Nady El Hajj, Thomas Haaf, Ulrich Zechner, Matthias Linke
Human spermatogonial stem cells (hSSCs) have potential in fertility preservation of pre-pubertal boys or in treatment of male adults suffering from meiotic arrest. Prior to therapeutic application, in-vitro propagation of rare hSSCs is mandatory. As the published data points to epigenetic alterations in long-term cell culture of spermatogonia (SPG), an initial characterisation of their DNA methylation state is important. Testicular biopsies from five adult normogonadotropic patients were converted into aggregate-free cell suspensions...
March 20, 2019: Molecular Human Reproduction
Tomoko Hirakawa, Kaei Nasu, Yoko Aoyagi, Kanetoshi Takebayashi, Ruofei Zhu, Hisashi Narahara
A number of genes involved in the pathogenesis of endometriosis are silenced by the hypermethylation of their promoter regions. We assessed the effect and mechanism of the DNA demethylating agent 5-aza-2'-deoxycytidine (5-aza-dC) (10 μM) on the cell cycle in human endometriotic cyst stromal cells (ECSCs) and normal endometrial stromal cells (NESCs) by flow cytometry. The DNA methylation status of G2/M checkpoint regulators were investigated by methylation-specific polymerase chain reaction (PCR). The expression of ATM and the effect of 5-aza-dC on its expression were also evaluated by quantitative reverse transcription-PCR and western blotting analysis...
March 14, 2019: Molecular Human Reproduction
Anya L Arthurs, Eugenie R Lumbers, Kirsty G Pringle
In early gestation, the human placental renin-angiotensin system (RAS) is upregulated and plays a role in placental development. Among other functions, signalling through the angiotensin II type 1 receptor (AT1R) initiates proliferation. Many microRNAs (miRNAs) targeting placental RAS mRNAs are downregulated at this time. We propose that in early gestation miRNAs that target the placental RAS are downregulated, allowing for the increased RAS expression and proliferation required for adequate placentation. HTR-8/SVneo cells (an immortalized human trophoblast cell line) were used to assess the effect of nine miRNA mimics (at 0...
March 14, 2019: Molecular Human Reproduction
Elizabeth G Bromfield, Jessica L H Walters, Shenae L Cafe, Ilana R Bernstein, Simone J Stanger, Amanda L Anderson, R John Aitken, Eileen A McLaughlin, Matthew D Dun, Barend M Gadella, Brett Nixon
Oxidative stress is a major aetiology in many pathologies, including that of male infertility. Recent evidence in somatic cells has linked oxidative stress to the induction of a novel cell death modality termed ferroptosis. However, the induction of this iron-regulated, caspase-independent cell death pathway has never been explored outside of the soma. Ferroptosis is initiated through the inactivation of the lipid repair enzyme glutathione peroxidase 4 (GPX4) and is exacerbated by the activity of arachidonate 15-lipoxygenase (ALOX15), a lipoxygenase enzyme that facilitates lipid degradation...
March 13, 2019: Molecular Human Reproduction
S C Berneau, P T Ruane, D R Brison, S J Kimber, M Westwood, J D Aplin
Implantation failure is an important impediment to increasing success rates in assisted reproductive technologies. Knowledge of the cascade of morphological and molecular events at implantation remains limited. Cell surface CD44 and hyaluronate (HA) have been reported in the uterus, but a role in intercellular interaction at implantation remains to be evaluated. Mouse embryos were co-cultured with human Ishikawa endometrial epithelial monolayers over 2 days. Attachment was tenuous during the first 24 h, after which it became stable, leading to breaching of the monolayer...
March 13, 2019: Molecular Human Reproduction
Yan Li, Yungai Xiang, Yuxia Song, Lijing Wan, Guo Yu, Li Tan
It is well established that microRNA (miRNA) expression profiles are altered in patients with polycystic ovary syndrome (PCOS). In addition, abnormal transforming growth factor beta (TGFB) signaling in granulosa cells is related to the pathological conditions of PCOS. However, the function of dysregulated miRNAs in PCOS is still unclear. In this study, we aimed to elucidate the roles of specific miRNAs in PCOS. We collected follicular fluid from 46 patients with PCOS and 32 healthy controls. Granulosa cells (GCs) were separated and the levels of six candidate miRNAs were determined by quantitative RT-PCR...
March 13, 2019: Molecular Human Reproduction
D D Manavella, L Cacciottola, V L Payen, C A Amorim, J Donnez, M M Dolmans
Adipose tissue-derived stem cells (ASCs) have multilineage differentiation potential, proangiogenic properties, and the ability to enhance vascularization in xenografted human ovarian tissue. The aim of the present study was to identify the mechanisms behind the proangiogenic effects of ASCs. For this purpose, severe combined immunodeficient (SCID) mice were grafted with frozen-thawed human ovarian tissue. ASCs were labeled by lentiviral transfection for expression of enhanced green fluorescent protein (eGFP), and human ovarian tissue was grafted using a previously described two-step procedure...
March 2, 2019: Molecular Human Reproduction
Sumio Ishijima
It has been shown that sperm flagellar motility is generated and modulated by metachronal sliding and two types of synchronous sliding of the outer doublet microtubules. Metachronal sliding propagates around the axoneme circumferentially from one doublet to another along the flagellum, whereas the two types of synchronous sliding occur synchronously throughout an extended region along the doublet microtubules. Oscillatory synchronous sliding occurs between most pairs of the nine doublet microtubules, whereas non-oscillatory synchronous sliding occurs between a specific pair of the nine doublet microtubules...
March 2, 2019: Molecular Human Reproduction
Matías D Gómez-Elías, María May, María José Munuce, Luis Bahamondes, Patricia S Cuasnicú, Débora J Cohen
Ulipristal acetate (UPA) is a selective progesterone receptor modulator used for emergency contraception that has proven to be highly effective in preventing pregnancy when taken up to 120 h after unprotected sexual intercourse. Even though it may act mainly by delaying or inhibiting ovulation, additional effects of UPA on post-fertilization events cannot be excluded. Therefore, the aim of this study was to determine whether a single post-ovulatory dose of UPA could prevent pregnancy using the mouse as a pre-clinical model...
March 2, 2019: Molecular Human Reproduction
M J Freitas, J V Silva, C Brothag, B Regadas-Correia, M Fardilha, S Vijayaraghavan
In mouse and bovine sperm, GSK3 activity is inversely proportional to motility. Targeted disruption of the GSK3A gene in testis results in normal spermatogenesis, but mature sperm present a reduced motility, rendering male mice infertile. On the other hand, GSK3B testis-specific KO is fertile. Yet in human sperm, an isoform-specific correlation between GSK3A and sperm motility was never established. In order to analyze GSK3 function in human sperm motility, normospermic and asthenozoospermic samples from adult males were used to correlate GSK3 expression and activity levels with human sperm motility profiles...
March 2, 2019: Molecular Human Reproduction
S J Holdsworth-Carson, E M Colgrave, J F Donoghue, J N Fung, M L Churchill, S Mortlock, P Paiva, M Healey, G W Montgomery, J E Girling, P A W Rogers
Endometriotic lesions are composed in part of endometrial-like stromal cells, however, there is a shortage of immortalized human endometrial stromal cultures available for research. As genetic factors play a role in endometriosis risk, it is important that genotype is also incorporated into analysis of pathological mechanisms. Human telomerase reverse transcriptase (hTERT) immortalization (using Lenti-hTERT-green fluorescent protein virus) took place following genotype selection; 13 patients homozygous for either the risk or non-risk 'other' allele for one or more important endometriosis risk single nucleotide polymorphism on chromosome 1p36...
February 16, 2019: Molecular Human Reproduction
Carolyn M Mitchell, Jonathan J Hirst, Murray D Mitchell, Henry G Murray, Tamas Zakar
Inflammatory genes are expressed increasingly in the fetal membranes at late gestation triggering birth. Here we have examined whether epigenetic histone modifications contribute to the upregulation of proinflammatory genes in the amnion in late pregnancy and at labour. Amnion samples were collected from early pregnancy, at term in the absence of labour and after spontaneous birth. The expression of the labour-associated proinflammatory genes PTGS2, BMP2 and NAMPT was determined by reverse transcription-coupled quantitative real-time PCR (qRT-PCR)...
February 12, 2019: Molecular Human Reproduction
Anya L Arthurs, Eugenie R Lumbers, Sarah J Delforce, Andrea Mathe, Brian J Morris, Kirsty G Pringle
Human placental renin-angiotensin system (RAS) expression is highest in early gestation, at a time when placental oxygen tension is at its lowest (1-3%), and promotes placental development. Some miRNAs predicted to target RAS mRNAs are downregulated in early gestation. We tested the hypothesis that low oxygen suppresses expression of miRNAs that target placental RAS mRNAs, thus increasing concentrations of RAS mRNAs.HTR-8/SVneo cells were cultured in 1%, 5% and 20% oxygen for 48 h. Differences in miRNA expression were measured on an Affymetrix miRNA microarray (n = 3/group)...
February 6, 2019: Molecular Human Reproduction
Julio Buñay, Eduardo Larriba, Daniel Patiño-Garcia, Paulina Urriola-Muñoz, Ricardo D Moreno, Jesús Del Mazo
The increase in male idiopathic infertility has been associated with daily exposure to endocrine disruptors chemicals (EDCs). Nevertheless, the mechanisms of action in relation to dysregulating proteins and regulatory microRNAs are unknown.We combined proteomic and miRNome analyses of mouse testis chronically exposed to low doses of a define mixture of EDCs [phthalates: bis (2-ethylhexyl), dibutyl and benzyl-butyl; 4-nonylphenol and 4-tert-octylphenol], administered in the drinking water from conception until adulthood (post-natal day 60/75) and compared them with no-exposed control mice...
January 30, 2019: Molecular Human Reproduction
Peter Z Schall, Meghan L Ruebel, Uros Midic, Catherine A VandeVoort, Keith E Latham
The preimplantation period of life in mammals encompasses a tremendous amount of restructuring and remodeling of the embryonic genome and reprogramming of gene expression. These vast changes support metabolic activation and cellular processes that drive early cleavage divisions and enable the creation of the earliest primitive cell lineages. A major question in mammalian embryology is how such vast, sweeping changes in gene expression are orchestrated, so that changes in gene expression are exactly appropriate to meet the developmental needs of the embryo over time...
January 30, 2019: Molecular Human Reproduction
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