GDF9 and BMP15 Expressions and Fine Structure Changes During Folliculogenesis in Polycystic Ovary Syndrome

Abstract

Background:Polycystic ovary syndrome is the most frequently seen endocrine disorder in women of reproductive age with a prevalence of about 10%.Aims:To investigate the efficiency of growth differentiation factor 9 and bone morphogenetic protein 15 during folliculogenesis in a dehydroepiandrosterone-induced mouse Polycystic ovary syndrome model.Study Design:Animal experimentation.Methods:Mice were divided into 3 groups: control, vehicle and Polycystic ovary syndrome. Polycystic ovary syndrome model mice were developed by the injection of dehydroepiandrosterone dissolved in 0.1 mL of sesame oil. Ovarian tissues were examined for growth differentiation factor 9 and bone morphogenetic protein 15 using immunofluorescent labelling and electron microscopic examinations.Results:The immunoreactivity of growth differentiation factor 9 and bone morphogenetic protein 15 proteins decreased (p<0.05) in the Polycystic ovary syndrome group (27.73±8.43 and 24.85±7.03, respectively) compared with the control group (33.72±11.22 and 31.12±11.05, respectively) and vehicle group (33.95±10.75 and 29.99±10.72, respectively). Apoptotic changes were observed in granulosa cells, lipid vacuoles increased in Theca cells and thickening and irregularities were noted in the basal lamina of granulosa cells. An increased electron density in the zona pellucida in some of the multilaminar primary and secondary follicles in the Polycystic ovary syndrome model was also observed at the ultrastructural level.Conclusion:These results suggest that the decrease in the growth differentiation factor 9 and bone morphogenetic protein 15 expression initiated at the primary follicle stage effect the follicle development and zona pellucida structure and may cause subfertility or infertility in Polycystic ovary syndrome.

Alteration of TGFB1, GDF9, and BMPR2 gene expression in preantral follicles of an estradiol valerate-induced polycystic ovary mouse model can lead to anovulation, polycystic morphology, obesity, and absence of hyperandrogenism

“…In this study, the expression level of GDF9 was lower in preantral PCOS follicles. Karagul et al [ 6 ] also found reduced levels of GDF9 expression in primary follicles. Teixeira Filho et al [ 52 ] also reported the aberrant expression of GDF9 in oocytes of women with PCOS.…”

“…Folliculogenesis is fundamentally based on the secretion of various types of growth factors (GFs) by ovarian somatic cells [ 5 ]. Two major types of GFs are growth differentiation factor-9 (GDF9) and transforming growth factor-beta1 (TGF-β1) [ 6 , 7 ], which are necessary for folliculogenesis and cell proliferation, respectively. Bone morphogenetic protein (BMP)-15 is involved in folliculogenesis, including the growth and maturation of ovarian follicles, regulation of the sensitivity of granulosa cells to follicle-stimulating hormone (FSH), determination of the number of ovulated follicles, and prevention of granulosa cells from apoptosis.…”

Association between polymorphism in BMP15 and GDF9 genes and impairing female fecundity in diabetes type 2

“…Nonetheless, the BMP15 and GDF9 play a critical role in follicle development, oocyte maturation, ovulation, and embryo development [61]. However, the in vivo and in vitro studies have suggested that GDF9 and BMP15 polymorphism contribute to the formation of the pathogenesis of PCOS [3,62]. The A-G transition at position 704 of the BMP15 gene results in a nonconserved substitution of Y235C in the pro region of BMP15 proprotein that was associated with hypergonadotropic ovarian failure in women [4].…”

Ovarian Biomechanics: From Health to Disease

“…The follicles of patients with PCOS have polycystic ovaries with an increase in matrix hypertrophy; the granular cell substrate is thickened, and the electron density in the zona pellucida formed by secondary follicles increases. Ovarian drilling is often used for clinical treatment, and the mechanical forces generated in the process cause changes in the ovarian endocrine level, especially an luteinizing hormone decline (97,98). Presently, a mechanobiology-based treatment that ruptures the ovarian cortex through in vitro activation (IVA) temporarily interrupts the Hippo pathway and promotes the secondary development of follicles.…”