BMP system expression in GCs from polycystic ovary syndrome women and the in vitro effects of BMP4, BMP6, and BMP7 on GC steroidogenesis

Abstract

Background: The bone morphogenetic proteins (BMPs) are growth factors involved in the folliculogenesis. Alteration in their expression may compromise the reproductive process in disease such as the polycystic ovary syndrome (PCOS). This study investigated the expression and role of granulosa cell (GC) BMP from normal cycling and PCOS women. Methods and results: This prospective study was performed in GCs obtained from 14 patients undergoing IVF: i) six women with normal ovulatory cycles and tubal or male infertility and ii) eight women with PCOS. BMP2, BMP4, BMP5, BMP6, BMP7, and BMP8A and their receptors BMPR1A, BMPR1B, and BMPR2 were identified by RT-PCR in GCs from normally cycling and PCOS women. BMP4, BMP6, and BMP7 expressions were confirmed by immunohistochemistry. Quantitative transcript analysis showed the predominant expression of BMP6. In GCs from PCOS women, an overexpression of BMP6 (P!0.01) and BMPR1A mRNA (P!0.05) was observed. GC culture experiments demonstrated that basal estradiol (E 2 ) production was threefold higher but FSH-induced E 2 increment was twofold lower in PCOS compared with controls. In PCOS, BMP6 and BMP7 exerted a stimulatory effect on basal E 2 production while BMP4 and BMP6 inhibited FSH-induced E 2 production. FSH receptor and aromatase expression were not different between both groups. Conclusion: The BMP system is expressed in human GCs from normal cycling and PCOS women. The BMP may be involved in reproductive abnormalities found in PCOS.

BMP2, 4 and 6 and BMPR1B are altered from early stages of bovine cystic ovarian disease development

“…In this sense, Fatehi et al (2005) found no BMP4 protein expression in granulosa cells of growing follicles, despite having shown mRNA expression in granulosa and theca of antral follicles less than 8 mm in diameter. However, Glister et al (2010) and Kayani et al (2009) showed BMP4 mRNA expression and immunoreactive protein in both theca and granulosa cells, although BMP4 transcripts were more abundant in theca than in granulosa cells, in agreement with earlier immunocytochemical evidence in cattle (Glister et al 2004) and other species (Khalaf et al 2013).…”

Oocyte–somatic cell interactions in the human ovary—novel role of bone morphogenetic proteins and growth differentiation factors

“…The expression of BMP/GDF ligands and their receptors in human ovarian tissues is listed in Table III. In the human ovary, BMP2, BMP4, BMP5, BMP6, BMP7 and BMP8A are expressed in the GCs from normally cycling and polycystic ovary syndrome (PCOS) women (Khalaf et al ., 2013). In concert with this study, a study using isolated human pre-antral follicles that compared the expression levels of BMPs in five size-matched populations demonstrated that BMP6 and BMP15 are the most abundantly expressed ligands (Kristensen et al ., 2014).…”

“…(2002)Luteinized GCmRNA & ProteinRT-PCR, Western blotHuang et al . (2009)FF (0.83–53.9 ng/ml)ProteinELISAALK2Luteinized GCmRNART-qPCRKhalaf et al . (2013)ALK3Luteinized GCmRNA & ProteinRT-qPCR, IHCKhalaf et al .…”

“…Previous research has documented the expression of the mRNA and protein of BMP receptors in various follicular compartments of pre-antral and antral follicles of the human ovary (Khalaf et al ., 2013; Kristensen et al ., 2014). Among these receptors, BMPR2 is the most abundantly expressed type II receptor (Kristensen et al ., 2014).…”

Bone Morphogenetic Proteins are Significantly Reduced in the Follicular Fluid of Han Chinese Polycystic Ovary Syndrome Patients

“…In PCOS patients, Khalaf et al reported an over expression of BMP-6 and BMPR1A in granulosa cells. They showed that BMP-6 and BMP-7 exerted a stimulatory effect on basal E2 production while BMP-4 and BMP-6 inhibited FSH-induced E2 production [20]. It is now well recognized that BMPs play an important regulatory role in the mammalian ovary, central to follicular recruitment and selection mechanisms.…”