Genistein Inhibits Cell Proliferation and Stimulates Apoptosis in Human Coronary Artery Endothelial Cells

Background/Aims: Isoflavone genistein is a plant-derived compound structurally similar to estradiol, which behaves weakly estrogenic or anti-estrogenic in a cell- and concentration-dependent manner. Genistein has been hypothesized to have beneficial effects on vascular diseases, although the mechanism has been unclear. Here, we investigated whether genistein may play a role in atherogenesis by regulating human coronary artery endothelial cell (HCAEC) survival. Methods: HCAECs obtained from 48- to 53-year-old women (n = 3) were used and immunocytochemistry, cell proliferation assay and apoptosis assay were carried on HCAECs treated by genistein. Results: Immunocytochemistry confirmed that HCAECs in culture express predominantly ESR2. Cell proliferation assay revealed that following 72 h of genistein treatment, HCAEC proliferation decreased in a concentration-dependent (10(-10) to 10(-6) m) manner compared to control (p < 0.01). The anti-proliferative effect of genistein is inhibited by estradiol. Genistein (10(-8) M) also induced a time-dependent increase in the number of apoptotic HCAECs after 24-, 48- and 72-hour treatments as detected by TUNEL and morphological analyses. Conclusion: These findings suggest that genistein acts as an anti-proliferative agent on HCAECs. The anti-proliferative and proapoptotic effects of genistein on vascular cells underlie the proposed anti-atherogenic and cardioprotective role of genistein. Copyright (C) 2013 S. Karger AG, Base

Genistein Inhibits Cell Proliferation and Stimulates Apoptosis in Human Coronary Artery Endothelial Cells

Background/Aims: Isoflavone genistein is a plant-derived compound structurally similar to estradiol, which behaves weakly estrogenic or anti-estrogenic in a cell- and concentration-dependent manner. Genistein has been hypothesized to have beneficial effects on vascular diseases, although the mechanism has been unclear. Here, we investigated whether genistein may play a role in atherogenesis by regulating human coronary artery endothelial cell (HCAEC) survival. Methods: HCAECs obtained from 48- to 53-year-old women (n = 3) were used and immunocytochemistry, cell proliferation assay and apoptosis assay were carried on HCAECs treated by genistein. Results: Immunocytochemistry confirmed that HCAECs in culture express predominantly ESR2. Cell proliferation assay revealed that following 72 h of genistein treatment, HCAEC proliferation decreased in a concentration-dependent (10(-10) to 10(-6) m) manner compared to control (p < 0.01). The anti-proliferative effect of genistein is inhibited by estradiol. Genistein (10(-8) M) also induced a time-dependent increase in the number of apoptotic HCAECs after 24-, 48- and 72-hour treatments as detected by TUNEL and morphological analyses. Conclusion: These findings suggest that genistein acts as an anti-proliferative agent on HCAECs. The anti-proliferative and proapoptotic effects of genistein on vascular cells underlie the proposed anti-atherogenic and cardioprotective role of genistein. Copyright (C) 2013 S. Karger AG, Base

Basic aspects of implantation

Implantation, a critical step for establishing pregnancy, requires molecular and cellular events resulting in healthy uterine growth and differentiation, blastocyst adhesion, invasion and placental formation. Successful implantation requires a receptive endometrium, a normal and functional embryo at the blastocyst stage and a synchronized dialogue between maternal and embryonic tissues. In addition to the main role of sex steroids, the complexity of embryo implantation and placentation is exemplified by the number of cytokines and growth factors with demonstrated roles in these processes. Disturbances of the normal expression and action of these cytokines result in absolute or partial failure of implantation and abnormal placental formation in mice and humans. Members of the gp 130 cytokine family, interleukin (IL)-11 and leukaemia inhibitory factor, the transforming growth factor-beta superfamily, colony-stimulating factors, and the IL-1 and IL-15 systems are all crucial for successful implantation. In addition, chemokines are important both in recruiting specific cohorts of leukocytes to the implantation site, and in trophoblast trafficking and differentiation. This review provides discussion on embryonic and uterine factors that are involved in the process of implantation in autocrine, paracrine and/or juxtacrine manners at hormonal, cellular, and molecular levels

hCG: Biological Functions and Clinical Applications

Human chorionic gonadotropin (hCG) is produced primarily by differentiated syncytiotrophoblasts, and represents a key embryonic signal that is essential for the maintenance of pregnancy. hCG can activate various signaling cascades including mothers against decapentaplegic homolog 2 (Smad2), protein kinase C (PKC), and/or protein kinase A (PKA) in several cells types by binding to luteinizing hormone/chorionic gonadotropin receptor (LHCGR) or potentially by direct/indirect interaction with transforming growth factor beta receptor (TGFβR). The molecule displays specialized roles in promoting angiogenesis in the uterine endothelium, maintaining myometrial quiescence, as well as fostering immunomodulation at the maternal-fetal interface. It is a member of the glycoprotein hormone family that includes luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and follicle-stimulating hormone (FSH). The α-subunit of hCG displays homologies with TSH, LH, and FSH, whereas the β subunit is 80–85% homologous to LH. The hCG molecule is produced by a variety of organs, exists in various forms, exerts vital biological functions, and has various clinical roles ranging from diagnosis and monitoring of pregnancy and pregnancy-related disorders to cancer surveillance. This review presents a detailed examination of hCG and its various clinical applications

Alternative splicing of the mouse embryonic poly(A) binding protein () mRNA is regulated by an exonic splicing enhancer: a model for post-transcriptional control of gene expression in the oocyte-1

<p><b>Copyright information:</b></p><p>Taken from "Alternative splicing of the mouse embryonic poly(A) binding protein () mRNA is regulated by an exonic splicing enhancer: a model for post-transcriptional control of gene expression in the oocyte"</p><p></p><p>Molecular Human Reproduction 2008;14(7):393-398.</p><p>Published online 20 May 2008</p><p>PMCID:PMC2453241.</p><p>© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: [email protected]</p

Progestins Upregulate FKBP51 Expression in Human Endometrial Stromal Cells to Induce Functional Progesterone and Glucocorticoid Withdrawal: Implications for Contraceptive- Associated Abnormal Uterine Bleeding

<div><p>Use of long-acting progestin only contraceptives (LAPCs) offers a discrete and highly effective family planning method. Abnormal uterine bleeding (AUB) is the major side effect of, and cause for, discontinuation of LAPCs. The endometria of LAPC-treated women display abnormally enlarged, fragile blood vessels, decreased endometrial blood flow and oxidative stress. To understanding to mechanisms underlying AUB, we propose to identify LAPC-modulated unique gene cluster(s) in human endometrial stromal cells (HESCs). Protein and RNA isolated from cultured HESCs treated 7 days with estradiol (E₂) or E₂+ medroxyprogesterone acetate (MPA) or E₂+ etonogestrel (ETO) or E₂+ progesterone (P4) were analyzed by quantitative Real-time (q)-PCR and immunoblotting. HSCORES were determined for immunostained-paired endometria of pre-and 3 months post-Depot MPA (DMPA) treated women and ovariectomized guinea pigs (GPs) treated with placebo or E₂ or MPA or E₂+MPA for 21 days. In HESCs, whole genome analysis identified a 67 gene group regulated by all three progestins, whereas a 235 gene group was regulated by E₂+ETO and E₂+MPA, but not E₂+P4. Ingenuity pathway analysis identified glucocorticoid receptor (GR) activation as one of upstream regulators of the 235 MPA and ETO-specific genes. Among these, microarray results demonstrated significant enhancement of FKBP51, a repressor of PR/GR transcriptional activity, by both MPA and ETO. q-PCR and immunoblot analysis confirmed the microarray results. In endometria of post-DMPA <i>versus</i> pre-DMPA administered women, FKBP51 expression was significantly increased in endometrial stromal and glandular cells. In GPs, E₂+MPA or MPA significantly increased FKBP51 immunoreactivity in endometrial stromal and glandular cells <i>versus</i> placebo- and E₂-administered groups. MPA or ETO administration activates GR signaling and increases endometrial FKBP51 expression, which could be one of the mechanisms causing AUB by inhibiting PR and GR-mediated transcription. The resultant PR and/or GR-mediated functional withdrawal may contribute to associated endometrial inflammation, aberrant angiogenesis, and bleeding.</p></div

Unfolded protein response prevents blastocyst formation during preimplantation embryo development in vitro

Objective: To study the effect of increased endoplasmic reticulum (ER) stress as a major nongenomic mechanism for arrested blastocyst development