HMGA2-induced epithelial –mesenchymal transition is reversed by let-7d in intrauterine adhesions
In this study, we demonstrate that the mRNA and protein levels of high mobility group AT-hook 2 (HMGA2) were increased by nearly 3-fold (P <  0.0001) and 5-fold (P = 0.0095) in the endometrial epithelial cells (EECs) of IUA patients (n = 18) compared to controls.In vivo andin vitro models of endometrial fibrosis also confirmed the overexpression of HMGA2 in EECs.In vitro cell experiments indicated that overexpression of HMGA2 promoted the epithelial –mesenchymal transition (EMT) while knockdown of HMGA2 reversed transforming growth factor-β-induced EMT. A dual luciferase assay confirmed let-7d microRNA do...
Source: Molecular Human Reproduction - December 11, 2020 Category: Molecular Biology Source Type: research

Placental multipotent mesenchymal stromal cell-derived Slit2 may regulate macrophage motility during placental infection
In this study, we found that human placental multipotent mesenchymal stromal cells (hPMSCs) constitutively express Slit2. Therefore, we hypothesized that Slit2 expressed by hPMSCs could be involved in macrophage migration during placental inflammation through membrane cognate Roundabout (Robo) receptor signaling. In order to develop a preclinicalin vitro mouse model of hPMSCs in treatment of perinatal infection, RAW 264.7 cells were used in this study. Slit2 interacted with Robo4 that was highly expressed in RAW 264.7 macrophages: their interaction increased the adhesive ability of RAW 264.7 cells and inhibited migration. ...
Source: Molecular Human Reproduction - December 4, 2020 Category: Molecular Biology Source Type: research

Identification of genes associated with endometrial cell ageing
In this study, we conducted a qualitative examination of age-related changes in endometrial tissues and identified candidate genes as markers for uterine ageing. Gene expression patterns were assessed by two RNA-sequencing experiments using uterine tissues from wild type (WT) C57BL/6 mice. Gene expression data obtained by RNA-sequencing were validated by real-time PCR. Genes expressing the pro-inflammatory cytokinesIl17rb and chemokinesCxcl12 andCxcl14 showed differential expression between aged WT mice and a group of mice composed of 5- and 8-week-old WT (young) animals. Protein expression levels of the above-mentioned ge...
Source: Molecular Human Reproduction - December 1, 2020 Category: Molecular Biology Source Type: research

4-Hydroxyestradiol improves mouse embryo quality, epidermal growth factor-binding capability in vitro and implantation rates
This study was designed to determine whether culture media enriched in 4-OH-E2 could improve the quality and implantation rate of embryos obtainedin vitro, using bothin vitro andin vivo models. We also analyzed its effects on the epidermal growth factor (EGF)-binding capability of the embryos. Our results showed that the presence of 4-OH-E2 in the culture media of embryos during the morula to blastocyst transition increases embryo quality and attachment to endometrial cellsin vitro. 4-OH-E2 can also improve viable pregnancy rates of mouse embryos producedin vitro, reaching success rates that are similar to those from embry...
Source: Molecular Human Reproduction - November 25, 2020 Category: Molecular Biology Source Type: research

A combination of growth factors and cytokines alter preimplantation mouse embryo development, foetal development and gene expression profiles
AbstractWithin the maternal tract, the preimplantation embryo is exposed to an array of growth factors (GFs) and cytokines, most of which are absent from culture media used in clinical IVF. Whilst the addition of individual GFs and cytokines to embryo culture media can improve preimplantation mouse embryo development, there is a lack of evidence on the combined synergistic effects of GFs and cytokines on embryo development and further foetal growth. Therefore, in this study, the effect of a combined group of GFs and cytokines on mouse preimplantation embryo development and subsequent foetal development and gene expression ...
Source: Molecular Human Reproduction - November 5, 2020 Category: Molecular Biology Source Type: research

Mice born to females with oocyte-specific deletion of mitofusin 2 have increased weight gain and impaired glucose homeostasis
In conclusion, this study suggests a link between disrupted mitochondrial/ER function in oocytes and increased risk of metabolic diseases in the progeny. Future studies should determine whether MERC architecture and function are altered in oocytes from obese females, which might contribute toward transgenerational transmission of metabolic diseases. (Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - October 28, 2020 Category: Molecular Biology Source Type: research

Two  human menopausal gonadotrophin (hMG) preparations display different early signaling in vitro
AbstractCommercial hMG drugs are marketed for the treatment of infertility and consist of highly purified hormones acting on receptors expressed in target gonadal cells. Menopur® and Meriofert® are combined preparation of FSH and hCG and are comparedin vitro herein. To this purpose, the molecular composition of the two drugs was analyzed by immunoassay. The formation of FSH receptor and LH/hCG receptor (FSHR; LHCGR) heteromer, intracellular Ca2+ and cAMP activation, β-arrestin 2 recruitment and the synthesis of progesterone and estradiol were evaluated in transfected HEK293 and human primary granulosa lutein cells treat...
Source: Molecular Human Reproduction - October 21, 2020 Category: Molecular Biology Source Type: research

A mouse model reveals the events and underlying regulatory signals during the gonadotrophin-dependent phase of follicle development
In this study, pregnant mare ’s serum GTH was used to induce GTH-dependent folliculogenesis in mice, following which the developmental events that follicles undergo, as well as the underlying regulatory signals, were investigated at both the morphological and transcriptomic level. GTH-dependent folliculogenesis consisted of t hree phases: preparation, rapid growth and decelerated growth. In the preparation phase, comprising the first 12 h, granulosa cells completed the preparations for proliferation and differentiation, shifted energy metabolism to glycolysis, and reduced protein synthesis and processing. The rapid gro...
Source: Molecular Human Reproduction - October 16, 2020 Category: Molecular Biology Source Type: research

A novel xeno-organoid approach: exploring the crosstalk between human iPSC-derived PGC-like and rat testicular cells
AbstractSpecification of germ cell-like cells from induced pluripotent stem cells has become a clinically relevant tool for research. Research on initial embryonic processes is often limited by the access to foetal tissue, and in humans, the molecular events resulting in primordial germ cell (PGC) specification and sex determination remain to be elucidated. A deeper understanding of the underlying processes is crucial to describe pathomechanisms leading to impaired reproductive function. Several protocols have been established for the specification of human pluripotent stem cell towards early PGC-like cells (PGCLC), curren...
Source: Molecular Human Reproduction - October 13, 2020 Category: Molecular Biology Source Type: research

Extracellular vesicles miRNA-21: a potential therapeutic tool in premature ovarian dysfunction
This study aims to isolate AFMSC-derived extracellular vesicles (EVs) and investigate their abundancy for the anti-apoptotic miRNA-21 as a means of ovarian restoration. Female rats were divided into healthy controls and POD-induced groups. The POD induced groups were subdivided into three groups according to the therapies they received: placebo-treated POD, AFMSC and EVs groups. Rats were assessed for serum anti-M üllerian hormone (AMH) levels, ovarian caspase 3 and PTEN protein levels in the ovarian lysate. Total follicular counts (TFCs) were estimated from stained ovarian sections. Functional recovery was investigated t...
Source: Molecular Human Reproduction - October 13, 2020 Category: Molecular Biology Source Type: research

Unscrambling the oocyte and the egg: clarifying terminology of the female gamete in mammals
AbstractMost reproductive biologists who study female gametes will agree with the 16th century anatomist William Harvey ’s doctrine: ‘Ex Ovo Omnia’. This phrase, which literally translates to ‘everything from the egg’, recognizes the centrality of the egg in animal development. Eggs are most impressive cells, capable of supporting development of an entirely new organism following fertilization or parthenogenetic activation. Not so unifo rmly embraced in the field of reproductive biology is the nomenclature used to refer to the female germ cell. What is an oocyte? What is an egg? Are these terms the same, differen...
Source: Molecular Human Reproduction - October 6, 2020 Category: Molecular Biology Source Type: research

Sex-specific epigenetic profile of inner cell mass of mice conceived in vivo or by IVF
This study was performed to evaluate the epigenetic (using whole-genome bisulfite sequencing (WGBS) and assay for transposase-accessible chromatin using sequencing (ATAC-seq)) and transcriptomic changes (using RNA-seq) occurring in the inner cell mass (ICM) of male or female mouse embryos generatedin vivo or by IVF. We found that the ICM of IVF embryos, compared to thein-vivo ICM, differed in 3% of differentially methylated regions (DMRs), of which 0.1% were located on CpG islands. ATAC-seq revealed that 293 regions were more accessible and 101 were less accessible in IVF embryos, while RNA-seq revealed that 21 genes were ...
Source: Molecular Human Reproduction - October 3, 2020 Category: Molecular Biology Source Type: research

Annexin A2 acts as an adherent molecule under the regulation of steroids during embryo implantation
AbstractWe previously showed that annexin A2 (Axna2) was transiently expressed at the embryo-uterine luminal epithelium interface during the window of implantation and was involved in mouse embryo implantation. At the same time, Axna2 was reported to be upregulated in human receptive endometrium, which was critical for embryo attachment as an intracellular molecule. Here, we identified Axna2 as a membrane-bound molecule on human endometrial epithelial cells and trophoblast cells, and the outer surface membrane-bound Axna2 was involved in human embryo attachment. In addition, physiological levels of estrogen and progesteron...
Source: Molecular Human Reproduction - October 3, 2020 Category: Molecular Biology Source Type: research

Embryonic fatty acid metabolism in diabetic pregnancy: the difference between embryoblasts and trophoblasts
In conclusion, maternal diabetes mellitus alters embryonic FA metabolism differently in EB and TB, indicating a lineage-specific metabolic adaptive response. (Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - September 26, 2020 Category: Molecular Biology Source Type: research

Revisiting the action of steroids and triterpenoids on the human sperm Ca2+ channel CatSper
In conclusion, this study supports the claim that the steroids estradiol, testosterone and hydrocortisone act agonistically on CatSper in human sperm cells, thereby mimicking the effect of progesterone, and that lupeol and pristimerin do not act as inhibitors of human CatSper. (Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - September 14, 2020 Category: Molecular Biology Source Type: research