Dexamethasone-induced intrauterine growth restriction modulates expression of placental vascular growth factors and fetal and placental growth
In this study, a model of growth restriction in mice was established through maternal administration of dexamethasone during late gestation. We hypothesised that GC overexposure may adversely affect placental angiogenesis and fetal and placental growth. Female BALB/c mice were randomly assigned to control or dexamethasone treatment, either left to give birth or euthanised on days 15, 16, 17 and 18 of gestation followed by collection of maternal and fetal tissue. The IUGR rate increased to 100% in the dexamethasone group (8 mg/kg body weight on gestational days 14 and 15) and pups had clinical features of symmetrical IUG...
Source: Molecular Human Reproduction - February 2, 2021 Category: Molecular Biology Source Type: research
Heparin fragments induce cervical inflammation by recruiting immune cells through Toll-like receptor 4 in nonpregnant mice
In conclusion, our findings suggest that a TLR4/IRF3-mediated innate immune response in the cervical mucosa is induced by gsHep. This low anticoagulant heparin version, a novel TLR4 agonist, could contribute to human cervical ripening during the initiation of labour. (Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - January 28, 2021 Category: Molecular Biology Source Type: research
Aspirin reduces sFlt-1-mediated apoptosis of trophoblast cells in preeclampsia
In conclusion, aspirin reverses the endothelial dysfunction a nd oxidative stress caused by sFlt-1 and thus reduces apoptosis of preeclamptic trophoblasts by inactivating NF-κB signalling pathway. (Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - January 25, 2021 Category: Molecular Biology Source Type: research
Use of selective PGE2 receptor antagonists on human endometriotic stromal cells and peritoneal macrophages
AbstractNon-hormonal therapeutic strategies for endometriosis are needed. The aim of this study was to characterize the effects of prostaglandin (PG)E2 receptor inhibitors to explore their potential as novel therapeutic strategies for endometriosis. The expression of PGE2 receptors (EP2 and EP4) in donated tissues from human ovarian endometriosis, adenomyosis and peritoneal endometriosis was examined using immunohistochemistry. Human endometriotic stromal cells (ESC) isolated from ovarian endometriotic tissue and peritoneal macrophages were treated with EP2 and EP4 antagonists. cAMP accumulation and the effect of EP antago...
Source: Molecular Human Reproduction - January 19, 2021 Category: Molecular Biology Source Type: research
Biophysical optimization of preimplantation embryo culture: what mechanics can offer ART
AbstractOwing to the rise of ART and mounting reports of epigenetic modification associated with them, an understanding of optimal embryo culture conditions and reliable indicators of embryo quality are highly sought after. There is a growing body of evidence that mechanical biomarkers can rival embryo morphology as an early indicator of developmental potential and that biomimetic mechanical cues can promote healthy development in preimplantation embryos. This review will summarize studies that investigate the role of mechanics as both indicators and promoters of mammalian preimplantation embryo development and evaluate th...
Source: Molecular Human Reproduction - January 8, 2021 Category: Molecular Biology Source Type: research
Endoplasmic reticulum stress: a key regulator of the follicular microenvironment in the ovary
ABSTRACTIntra-ovarian local factors regulate the follicular microenvironment in coordination with gonadotrophins, thus playing a crucial role in ovarian physiology as well as pathological states such as polycystic ovary syndrome (PCOS). One recently recognized local factor is endoplasmic reticulum (ER) stress, which involves the accumulation of unfolded or misfolded proteins in the ER related to various physiological and pathological conditions that increase the demand for protein folding or attenuate the protein-folding capacity of the organelle. ER stress results in activation of several signal transduction cascades, col...
Source: Molecular Human Reproduction - January 7, 2021 Category: Molecular Biology Source Type: research
The role of ATP in the differential ability of Sr2+ to trigger Ca2+ oscillations in mouse and human eggs
AbstractAt fertilization in mice and humans, the activation of the egg is caused by a series of repetitive Ca2+ oscillations which are initiated by phospholipase-C(zeta) ζ that generates inositol-1,4,5-trisphophate (InsP3). Ca2+ oscillations and egg activation can be triggered in mature mouse eggs by incubation in Sr2+ containing medium, but this does not appear to be effective in human eggs. Here, we have investigated the reason for this apparent difference using mouse eggs, and human eggs that failed to fertilize after IVF or ICSI. Mouse eggs incubated in Ca2+-free, Sr2+-containing medium immediately underwent Ca2+ osci...
Source: Molecular Human Reproduction - January 5, 2021 Category: Molecular Biology Source Type: research
Epididymosomes: the black box of Darwin ’s pangenesis?
AbstractDarwin, in the pangenesis theory, imagined particles, named as ‘gemmules’, which are released from all (‘pan’) cells of the body. By cell–cell communication and also circulation through the body, they finally reach the germ cells to participate in the generation (‘genesis’) of the new individual. It has been shown that circulatory exosomes are aff ected by environmental stressors and they can reach the parental germ cells. Therefore, in the mirror of his theory, circulatory exosomes could interact with epididymosomes: epididymis-derived exosomes which have a wide spectrum of variation in content and s...
Source: Molecular Human Reproduction - January 4, 2021 Category: Molecular Biology Source Type: research
The role of Wnt signaling in male reproductive physiology and pathology
AbstractAccumulating evidence has shown that Wnt signaling is deeply involved in male reproductive physiology, and malfunction of the signal path can cause pathological changes in genital organs and sperm cells. These abnormalities are diverse in manifestation and have been constantly found in the knockout models of Wnt studies. Nevertheless, most of the research solely focused on a certain factor in the Wnt pathway, and there are few reports on the overall relation between Wnt signals and male reproductive physiology. In our review, Wnt findings relating to the reproductive system were sought and summarized in terms of Wn...
Source: Molecular Human Reproduction - January 4, 2021 Category: Molecular Biology Source Type: research
Metformin: a novel promising option for fertility preservation during cyclophosphamide-based chemotherapy
In conclusion, concurrent metformin treatment during CP therapy could significantly preserve ovarian function and fertility and could be a promising novel fertility preserving agent during chemotherapy. The relatively acceptable cost and well-established long-term safety profiles of this old drug might prompt its further clinical application at a faster pace. (Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - January 4, 2021 Category: Molecular Biology Source Type: research
Genetic risk factors for endometriosis near estrogen receptor 1 and coexpression of genes in this region in endometrium
This study aimed to investigate hormonal and genetic regulation of genes in theESR1 region in human endometrium. Changes in serum oestradiol and progesterone concentrations and expression of hormone receptorsESR1 and progesterone receptor (PGR) were assessed in endometrial samples from 135 women collected at various stages of the menstrual cycle. Correlation between hormone concentrations, receptor expression and expression of genes in theESR1 locus was investigated. The effect of endometriosis risk variants on expression of genes in the region was analyzed to identify gene targets. Hormone concentrations and receptor expr...
Source: Molecular Human Reproduction - January 4, 2021 Category: Molecular Biology Source Type: research
Oligoasthenoteratospermia and sperm tail bending in PPP4C-deficient mice
AbstractProtein phosphatase 4 (PPP4) is a protein phosphatase that, although highly expressed in the testis, currently has an unclear physiological role in this tissue. Here, we show that deletion of PPP4 catalytic subunit genePpp4c in the mouse causes male-specific infertility. Loss of PPP4C, when assessed by light microscopy, did not obviously affect many aspects of the morphology of spermatogenesis, including acrosome formation, nuclear condensation and elongation, mitochondrial sheaths arrangement and ‘9 + 2’ flagellar structure assembly. However, the PPP4C mutant had sperm tail bending defects (head-bent-back)...
Source: Molecular Human Reproduction - December 30, 2020 Category: Molecular Biology Source Type: research
Humanin regulates oxidative stress in the ovaries of polycystic ovary syndrome patients via the Keap1/Nrf2 pathway
In this study, we investigated whether humanin expression differs in the granulosa cells (GCs) of PCOS patients versus controls, and whether humanin alleviates OS in PCOS ovaries. Sixteen PCOS patients and 28 age- and BMI-matched controls undergoing IVF were recruited, and their serum, follicular fluid and GCs were collected for humanin analysis. Dehydroepiandrosterone-induced rat PCOS models, and vitamin K3-induced OS COV434 cell lines were applied to investigate the mechanism. Humanin expression was significantly down-regulated in the ovaries of PCOS patients relative to those of non-PCOS patients. Exogenous humanin supp...
Source: Molecular Human Reproduction - December 26, 2020 Category: Molecular Biology Source Type: research
Premature ovarian ageing following heterozygous loss of Senataxin
AbstractPremature loss of ovarian activity before 40 years of age is known as primary ovarian insufficiency (POI) and occurs in ∼1% of women. A more subtle decline in ovarian activity, known as premature ovarian ageing (POA), occurs in ∼10% of women. Despite the high prevalence of POA, very little is known regarding its genetic causation. Senat axin (SETX) is an RNA/DNA helicase involved in repair of oxidative stress-induced DNA damage. Homozygous mutation ofSETX leads to the neurodegenerative disorder, ataxia oculomotor apraxia type 2 (AOA2). There have been reports of POI in AOA2 females suggesting a link between ...
Source: Molecular Human Reproduction - December 18, 2020 Category: Molecular Biology Source Type: research
Relevance of angiogenesis in autoimmune testis inflammation
AbstractExperimental autoimmune orchitis (EAO) is a useful model to study organ-specific autoimmunity and chronic testicular inflammation. This model reflects testicular pathological changes reported in immunological infertility in men. Progression of EAO in rodents is associated with a significantly increased percentage of testicular endothelial cells and interstitial testicular blood vessels, indicating an ongoing angiogenic process. Vascular endothelial growth factor A (VEGFA), the main regulator of physiological and pathological angiogenesis, can stimulate endothelial cell proliferation, chemotaxis and vascular permeab...
Source: Molecular Human Reproduction - December 12, 2020 Category: Molecular Biology Source Type: research
