Serum GDF9 and BMP15 as potential markers of ovarian function in women with and without polycystic ovary syndrome

Abstract

Objective Growth differentiation factor‐9 (GDF9) and bone morphogenetic protein‐15 (BMP15) are critical paracrine regulators of female fertility and are predominantly expressed by oocytes. However, it is unknown if serum concentrations reflect changes in ovarian function and/or reproductive endocrine disorders. This study aimed to determine if serum GDF9/BMP15 are associated with ovarian, pituitary, oestrogenic, androgenic and metabolic characteristics and the ovarian pathologies, polycystic ovarian morphology (PCOM) and polycystic ovary syndrome (PCOS). Design Women aged 21−45 years (n = 381) were included from a cross‐sectional study at the National University Hospital, Singapore. Patients: Participants were volunteers and patients with possible PCOS. Measurements: Anthropometric measurements, transvaginal ultrasound scans and serum sampling were performed and a questionnairecompleted. Serum GDF9 and BMP15 concentrations were matched with menstrual cycle length, ovarian protein and steroid hormone production, pituitary hormone production and metabolic assessments in women with PCOM or PCOS and those with neither (control). Results Serum GDF9 and BMP15 were detectable in 40% and 41% of women, respectively and were positively correlated with each other (r = 0.08, p = 0.003). GDF9, but not BMP15, was positively correlated with ovarian volume (p = 0.02) and antral follicle count (AFC) (p = 0.004), but not with anti‐Müllerian hormone (p = 0.05). However, serum GDF9 and BMP15 concentrations were not significantly different between control, PCOM and PCOS women, nor associated with androgenic or metabolic PCOS features. However, the relationship between GDF9 and AFC differed between control, PCOM and PCOS women (p = 0.02). Conclusions Serum GDF9 and BMP15 concentrations somewhat reflect ovarian but not androgenic or metabolic characteristics of PCOS, with increased GDF9 reflecting high AFC as seen in PCOM/PCOS.

Serum Follicular Fluid Growth Differentiation Factor 9 (GDF-9) and Bone Morphogenic Protein 15 (BMP-15) as Markers of Ovarian Reserve

“…showed that serum and follicular fluid BMP-15 but not GDF-9 decreased with the age of the female [19]. Another study showed a significant positive correlation between GDF-9 and female age [25].…”

“…The levels of both factors in the follicular fluid can be used to determine the quality (maturity) of the oocytes retrieved following stimulation. The novelty of our study is that previous researches studied serum concentrations of BMP15 and GDF9 during the in vitro fertilization (IVF) in women with reproductive pathologies and in women with PCOS and their relations to the number of produced oocytes [18,19]. Besides, others studied the correlations of serum, follicular fluid GDF-9 and BMP-15 concentration and ICSI outcome represented by oocytes, embryos number, their qualities and chemical pregnancy rate [22].…”

“…BMP-15 and GDF-9 measurements in serum could have diagnostic usefulness in predicting female fertility potential and oocyte quality, as both are specifically secreted from primordial and primary follicles and their levels can give an idea about the number of stored follicles within the follicular pool [19]. Hence, this study aims to assess the ability of serum, follicular fluid, GDF-9, and BMP-15 to predict ovarian reserve and whether they can be used as ovarian reserve tests either alone or together with AMH and AFC.…”

Comparing GDF9 in mature follicles and clinical outcomes across different PCOS phenotype

“…Studies have shown that increased GDF9 levels in FF are significantly correlated with oocyte maturation and embryo quality [ 12 , 13 ], suggesting a potential relationship between GDF9 levels and oocyte competence. GDF9 was an important biomarker for predicting oocyte development potential [ 14 ]. The FF and CCs are by-products of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) which can reflect the ovarian microenvironment to a certain extent and directly reflect the oocyte metabolism and quality [ 15 ].…”

Impact of GnRH agonist and GnRH antagonist on GDF9 and BMP15 expression in mouse ovaries and oocyte development

“…Growth differentiation facor9 (GDF9) and bone morphogenetic protein15 (BMP15) are essential proteins secreted by oocytes in the primary follicle, playing a crucial role in organizing the surrounding granulosa and theca cells into the oocyte-cumulus-follicle complex. These two factors are also associated with cumulus cell proliferation, apoptosis, metabolism, and expansion, which are fundamental for embryo developmental competency and female fertility (D'Occhio et al, 2020;Alama et al, 2013;D' Occhio et al, 2020;Riepsamen et al, 2023). Consequently, GDF9 and BMP15 have become valuable markers used to assess oocyte quality and competency in recent research (Gong et al, 2021;Kousheh et al, 2022;Yang et al, 2020).…”