Excess fibronectin 1 participates in pathogenesis of pre-eclampsia by promoting apoptosis and autophagy in vascular endothelial cells
AbstractPlasma fibronectin 1 (FN1) levels are elevated in individuals with pre-eclampsia (PE), which may be applied as a possible b marker for vascular endothelial injury during PE. In the present study, the possible role of FN1 in the pathogenesis of PE and regulation of apoptosis and autophagy in vascular endothelial cells was explored. Plasma FN1 levels in 80 patients with PE and 40 healthy pregnant individuals were measured using ELISA to verify its relationship with the severity of PE. pcDNA3.1-FN1 or FN1-small interfering (si) RNA was used to manipulate the expression of FN1 in human umbilical vein endothelial cells ...
Source: Molecular Human Reproduction - April 20, 2021 Category: Molecular Biology Source Type: research
Limited proteolysis by acrosin affects sperm-binding and mechanical resilience of the mouse zona pellucida
AbstractThe encounter of oocyte and sperm is the key event initiating embryonic development in mammals. Crucial functions of this existential interaction are determined by proteolytic enzymes, such as acrosin, carried in the sperm head acrosome, and ovastacin, stored in the oocyte cortical granules. Ovastacin is released upon fertilisation to cleave the zona pellucida, a glycoprotein matrix surrounding the oocyte. This limited proteolysis hardens the oocyte envelope, and thereby provides a definitive block against polyspermy and protects the developing embryo. On the other hand, acrosin, the renowned and most abundant acro...
Source: Molecular Human Reproduction - March 29, 2021 Category: Molecular Biology Source Type: research
An agenda for the year 2021 and onwards
I am honored to become the new Editor-in-Chief of MHR, which now enters its 26th year as a self-standing ESHRE Journal. I bring my experience of a number of years as Deputy Editor, my stamina and my passion into my new role, but also some trepidation, when I recall who my predecessors were —starting from Founder Editor and Nobel Laureate Robert Edwards. I wish to thank outgoing Editor-in-Chief, Keith Jones, and his immediate predecessor, Chris Barratt, who both gave me unwavering support during my tenure with them. They stewarded the Journal to its current position as a reference po int in the landscape of scholarly publ...
Source: Molecular Human Reproduction - March 23, 2021 Category: Molecular Biology Source Type: research
RNA N6-methyladenosine modification, spermatogenesis, and human male infertility
AbstractRNA N6-methyladenosine (m6A) modification is one of the main forms of posttranscriptional modification, and its dysregulation is involved in a series of pathological processes. RNA m6A regulators, which mediate dynamic RNA m6A modification, are expressed in almost all types of testicular cells, including spermatogenetic cells and somatic cells. Cumulative studies have found that knockout of RNA m6A regulators in the testis leads to abnormal metabolism of the target mRNAs, which eventually causes spermatogenetic disorders and infertility. To date, a role for dysregulated RNA m6A modification in human male infertilit...
Source: Molecular Human Reproduction - March 22, 2021 Category: Molecular Biology Source Type: research
Genetic and epigenetic changes in the eutopic endometrium of women with endometriosis: association with decreased endometrial αvβ3 integrin expression
AbstractAbout 40% of women with infertility and 70% of women with pelvic pain suffer from endometriosis. The pregnancy rate in women undergoing IVF with low endometrial integrin αvβ3 (LEI) expression is significantly lower compared to the women with high endometrial integrin αvβ3 (HEI). Mid-secretory eutopic endometrial biopsies were obtained from healthy controls (C; n=3), and women with HEI (n=4) and LEI (n=4) and endometriosis. Changes in gene expression were assessed using human gene arrays and DNA methylation data were derived using 385 K Two-Array Promoter Arrays. Transcriptional analysis revealed that LEI and...
Source: Molecular Human Reproduction - March 9, 2021 Category: Molecular Biology Source Type: research
Tofacitinib alters STAT3 signaling and leads to endometriosis lesion regression
AbstractEndometriosis is a widespread gynecologic condition affecting up to 15% of women of reproductive age. The Janus kinase/signal transducer and activator of transcription (JAK/STAT3) pathway is upregulated in endometriosis and is a therapeutic target. Here we sought to determine the effect of Tofacitinib, a JAK inhibitor in widespread clinical use, on JAK/STAT signaling in endometriosis and lesion growth. Endometriosis was surgically induced in C57BL/6 mice using homologous uterine horn transplantation. Lesions were allowed to form over 4 weeks followed by Tofacitinib (10 mg/kg) or vehicle administered by oral ga...
Source: Molecular Human Reproduction - March 9, 2021 Category: Molecular Biology Source Type: research
Regulation of endoplasmic reticulum stress and trophectoderm lineage specification by the mevalonate pathway in the mouse preimplantation embryo
AbstractEarly embryos are vulnerable to environmental insults, such as medications taken by the mother. Due to increasing prevalence of hypercholesterolemia, more women of childbearing potential are taking cholesterol-lowering medications called statins. Previously, we showed that inhibition of the mevalonate pathway by statins impaired mouse preimplantation development, by modulating HIPPO signaling, a key regulator for trophectoderm (TE) lineage specification. Here, we further evaluated molecular events that are altered by mevalonate pathway inhibition during the timeframe of morphogenesis and cell lineage specification....
Source: Molecular Human Reproduction - March 2, 2021 Category: Molecular Biology Source Type: research
Downregulation of aromatase plays a dual role in preeclampsia
In conclusion, the downregulation of aromatase has a dual role in PE, among which the induction of the disease is the main role. Our study provides a potential novel method for the early prediction and treatment of PE. (Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - February 24, 2021 Category: Molecular Biology Source Type: research
Angiopoietin 2 stimulates trophoblast invasion via a mechanism associated with JNK signaling
In conclusion, we demonstrate that Ang-2 can stimulate EVT invasion via a mechanism associated with activation of both the Tie2 receptor and integrins, which appear to work through different pathways; Tie2 through the JNK/c-JUN pathway and integrins through an as yet unidentified pathway(s). We therefore propose that any alterations in Ang-2 expression in the decidua would lead to an imbalance in pro- and anti-invasive factors, disrupting regulation of EVT invasion and spiral artery remodeling and thereby contribute to the etiology of several complications of pregnancy. (Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - February 24, 2021 Category: Molecular Biology Source Type: research
Histone demethylase KDM4A overexpression improved the efficiency of corrected human tripronuclear zygote development
AbstractHuman zygotes are difficult to obtain for research because of limited resources and ethical debates. Corrected human tripronuclear (ch3PN) zygotes obtained by removal of the extra pronucleus from abnormally fertilized tripronuclear (3PN) zygotes are considered an alternative resource for basic scientific research. In the present study, eight-cell and blastocyst formation efficiency were significantly lower in both 3PN and ch3PN embryos than in normal fertilized (2PN) embryos, while histone H3 lysine 9 trimethylation (H3K9me3) levels were much higher. It was speculated that the aberrant H3K9me3 level detected in ch3...
Source: Molecular Human Reproduction - February 18, 2021 Category: Molecular Biology Source Type: research
Guidelines for biomarker discovery in endometrium: correcting for menstrual cycle bias reveals new genes associated with uterine disorders
In conclusion, we demonstrate that menstrual cycle progression masks molecular biomarkers, provides new guidelines to unmask them and proposes a new classification that distinguishes between biomarkers of disorder or/and menstrual cycle progression. (Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - February 12, 2021 Category: Molecular Biology Source Type: research
Current mechanisms of primordial follicle activation and new strategies for fertility preservation
AbstractPremature ovarian insufficiency (POI) is characterized by symptoms caused by ovarian dysfunction in patients aged<40 years. It is associated with a shortened reproductive lifespan. The only effective treatment for patients who are eager to become pregnant is IVF/Embryo Transfer (ET) using oocytes donated by young women. However, the use of the technique is constrained by the limited supply of oocytes and ethica l issues. Some patients with POI still have some residual follicles in the ovarian cortex, which are not regulated by gonadotropin. These follicles are dormant. Therefore, activating dormant primordial...
Source: Molecular Human Reproduction - February 12, 2021 Category: Molecular Biology Source Type: research
Motility of efferent duct cilia aids passage of sperm cells through the male reproductive system
AbstractMotile cilia line the efferent ducts of the mammalian male reproductive tract. Several recent mouse studies have demonstrated that a reduced generation of multiple motile cilia in efferent ducts is associated with obstructive oligozoospermia and fertility issues. However, the sole impact of efferent duct cilia dysmotility on male infertility has not been studied so far either in mice or human. Using video microscopy, histological- and ultrastructural analyses, we examined male reproductive tracts of mice deficient for the axonemal motor protein DNAH5: this defect exclusively disrupts the outer dynein arm (ODA) comp...
Source: Molecular Human Reproduction - February 9, 2021 Category: Molecular Biology Source Type: research
Elucidating the role of long intergenic non-coding RNA 339 in human endometrium and endometriosis
ABSTRACTEndometriosis is a complex disease, influenced by genetic factors. Genetic markers associated with endometriosis exist at chromosome 1p36.12 and lead to altered expression of the long intergenic non-coding RNA 339 (LINC00339), however, the role of LINC00339 in endometriosis pathophysiology remains unknown. The aim of this work was to characterize the expression patterns ofLINC00339 mRNA in endometrium and endometriotic lesionsin situ and to determine the functional role of LINC00339 in human endometrium. We employed RNA-sequencing (RNA-seq), quantitative RT-PCR andin situ hybridization to investigate the abundance ...
Source: Molecular Human Reproduction - February 8, 2021 Category: Molecular Biology Source Type: research
Endometrial stromal cell proteomic analysis reveals LIM and SH3 protein 1 (LASP1) plays important roles in the progression of adenomyosis
In this study, we utilized two-dimensional gel electrophoresis combined with protein identification by mass spectrometry (2D/MS) proteomics analysis to compare the differential protein expression profile between the paired eutopic and ectopic ESCs (EuESCs and EcESCs) in adenomyosis, and a total of 32 significantly altered protein spots were identified. Among which, the expression of LIM and SH3 protein 1 (LASP1) was increased significantly in EcESCs compared to EuESCs. Immunohistochemical assay showed that LASP1 was overexpressed in the stromal cells of ectopic endometriums compared to eutopic endometriums; further functio...
Source: Molecular Human Reproduction - February 5, 2021 Category: Molecular Biology Source Type: research
