Intrafollicular Concentrations of the Oocyte-secreted Factors GDF9 and BMP15 Vary Inversely in Polycystic Ovaries

J Clin Endocrinol Metab. 2022 Jul 14;107(8):e3374-e3383. doi: 10.1210/clinem/dgac272.

Abstract

Context: The oocyte-secreted factors growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) play essential roles in follicle development and oocyte maturation, and aberrant regulation might contribute to the pathogenesis of polycystic ovary syndrome.

Objective: Are there measurable differences in concentrations of GDF9, BMP15, and the GDF9/BMP15 heterodimer in small antral follicle fluids from women with and without polycystic ovaries (PCO)?

Design and setting: Follicle fluids (n = 356) were collected from 4- to 11-mm follicles in unstimulated ovaries of 87 women undergoing ovarian tissue cryopreservation for fertility preservation.

Patients: Twenty-seven women with PCO were identified and 60 women without PCO-like characteristics (non-PCO women) were matched according to age and follicle size.

Main outcome measures: Intrafollicular concentrations of GDF9, BMP15, GDF9/BMP15 heterodimer, anti-Mullerian hormone (AMH), inhibin-A and -B, total inhibin, activin-B and -AB, and follistatin were measured using enzyme-linked immunosorbent assays.

Results: The detectability of GDF9, BMP15, and the GDF9/BMP15 heterodimer were 100%, 94.4%, and 91.5%, respectively, and concentrations were significantly negatively correlated with increasing follicle size (P < 0.0001). GDF9 was significantly higher in women with PCO (PCO: 4230 ± 189 pg/mL [mean ± SEM], n = 188; non-PCO: 3498 ± 199 pg/mL, n = 168; P < 0.03), whereas BMP15 was lower in women with PCO (PCO: 431 ± 40 pg/mL, n = 125; non-PCO: 573 ± 55 pg/mL, n = 109; P = 0.10), leading to a significantly higher GDF9:BMP15 ratio in women with PCO (P < 0.01). Significant positive associations between BMP15 and AMH, activins, and inhibins in non-PCO women switched to negative associations in women with PCO.

Conclusions: Intrafollicular concentrations of GDF9 and BMP15 varied inversely in women with PCO reflecting an aberrant endocrine environment. An increased GDF9:BMP15 ratio may be a new biomarker for PCO.

Keywords: BMP15; GDF9; PCOS; antral follicle; cumulin; follicle fluid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Mullerian Hormone / analysis
  • Anti-Mullerian Hormone / metabolism
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Bone Morphogenetic Protein 15* / analysis
  • Bone Morphogenetic Protein 15* / metabolism
  • Female
  • Follicular Fluid* / chemistry
  • Growth Differentiation Factor 9* / analysis
  • Growth Differentiation Factor 9* / metabolism
  • Humans
  • Inhibins / metabolism
  • Oocytes* / metabolism
  • Polycystic Ovary Syndrome* / diagnosis
  • Polycystic Ovary Syndrome* / metabolism
  • Transforming Growth Factor beta / metabolism

Substances

  • BMP15 protein, human
  • Biomarkers
  • Bone Morphogenetic Protein 15
  • GDF9 protein, human
  • Growth Differentiation Factor 9
  • Transforming Growth Factor beta
  • Inhibins
  • Anti-Mullerian Hormone