Purpose To detect expression of bone morphogenetic protein 15 (and growth

Purpose To detect expression of bone morphogenetic protein 15 (and growth differentiation factor 9 (in oocytes, and their receptor type 2 receptor for BMPs (in cumulus cells in women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF), and determine if expression correlate with hyperandrogenism in FF of PCOS patients. oocyte individually and in microdissected cumulus cells from cumulus-oocyte complexes retrieved from preovulatory follicles using qRT-PCR. Chemiluminescence and RIA assays were utilized for hormone assays. Results and expression per oocyte was higher among women with PCOS than the control group. A positive correlation was found between transcripts and hyperandrogenism in FF of PCOS patients. Progesterone values in FF were lower in the PCOS group. Conclusion We inferred that and transcript levels increase in mature PCOS oocytes after COH, and might inhibit the progesterone secretion by follicular cells in PCOS follicles, preventing premature luteinization in cumulus cells. expression in PCOS cumulus cells might be regulated by androgens. and as well as their receptors (e.g.and and expression in oocytes and/or CCs of infertile PCOS women undergoing in vitro fertilization and embryo transfer (IVF-ET) [20, 21]. The established role of and in oocyte competence, and recent findings that single-nucleotide polymorphism variants in these genes seem connected with hyperstimulation syndrome and anovulation and infertility in women with PCOS, led us to evaluate the expression of these genes in single mature oocytes and the expression of in their respective cumulus cells from women with PCOS. We also evaluated gene expression in oocytes between the former and control groups undergoing COH for IVF. In addition, we analyzed the levels of sex steroids present in the follicular fluid of immature and mature follicles, and pregnancy rates of the PCOS patients. Gene expression profiles of BMP receptors in cumulus cells have only been fragmentally reported, and their results showed that is hormonally regulated [22C24]. However, evaluation of transcripts of this gene in cumulus cells from PCOS women undergoing COH for IVF has not been thoroughly examined. The TGF superfamily of ligands interact with heterotetrameric complexes of type 1 and type 2 receptors (BMPR2). Thus, GDF9 activates the type 1 receptor Rabbit Polyclonal to TDG. (TGFRI or activin-like receptor 5(ALK5) [25] and BMP15 activates the BMPRIB receptor or activin-like receptor 6 (ALK6). Following ligand binding, TGFRI or BMPRIB recruits the BMPR2 Saquinavir that results in phosporylation of the type 1 receptor, which in turn activates the intracellular-signal-mediated (Smad) proteins [16, 26, 27]. Recently, the BMPR2 has been identified as the Saquinavir receptor that primarily modulates the cooperative effects of GDF9 and BMP15 on rat granulosa cells function, with BMPR2 having the greatest effect on BMP15 suppression of FSH-induced progesterone production [28]. Furthermore, the type 2 receptor is usually appointed as the most effective in BMP15 bioactivity [29]. Because the established role of and in oocyte competence and given the important role of BMPR2 in modulate the synergistic effects of GDF9 and BMP15, the specific aims of the present study were: 1) to assess the expression of these genes in single mature oocytes and the expression of in their respective cumulus cells from women with PCOS; 2) to evaluate the gene expression in oocytes between the former and control groups undergoing COH for IVF; and 3) to analyze if sex steroids levels in the follicular fluid of immature and mature follicles correlates with transcript levels of oocyte-secreted factors in MII-oocytes and BMPR2 in CCs, and pregnancy rates of the PCOS patients. Material and methods Patients The study was approved by the Clinical Ethics Committee and informed written consent was obtained from each of the participants, who donated their surplus oocytes. A total of 365 women received intracytoplasmic sperm injection (ICSI) from December 2007 to February 2009 at the Human Reproduction Division of the Faculty of Medicine of Ribeir?o Preto, University or college of S?o Paulo. Thirty-five of these women were diagnosed with PCOS (PCOS group), 86 women with regular menstrual cycle and with male factor infertility (according to the World Health Business [30] criteria for the examination and processing of human semen, with at least 1?% normal spermatozoa) were selected for control group and 244 with other causes of infertility were excluded. Only 18 PCOS women and 35 Saquinavir control women offered surplus oocytes and CCs and fulfilled inclusion criteria and were included in the study. PCOS was diagnosed according to the Rotterdam criteria [31]. Patients with endometriosis or any other disease that would interfere with the hypothalamus-pituitary-ovary axis were excluded from the study. The distribution of the sample was homogeneous among the group with PCOS and Control group: age (PCOS?=?33??3.31 and Control?=?33??4.25), weight (PCOS?=?67??10.20 and Control?=?62.30??11.13), body mass index (PCOS?=?26??7.42 and Control?=?24.03??4.92), FSH (PCOS?=?4.59??5.37 and Control?=?6??2.21), thyroid stimulating hormone (PCOS?=?1.90??0.85 and Control?=?1.97??6.88) e Prolactin (PCOS?=?13.42??14.83 and Control?=?11.50??7.84). The results were expressed as mean and standard deviation. Controlled ovarian hyperstimulation protocol A gonadotropin releasing hormone (GnRH) agonist (Synarel, Zodiac) was utilized for IVF and followed the standard long downregulation Saquinavir protocol. Recombinant follicle stimulating hormone (rFSH), with the.


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