Serum GDF9 and BMP15 As Potential Markers of Ovarian Function in Women with and Without Polycystic Ovary Syndrome

Overview

Journal Clin Endocrinol (Oxf)

Specialty Endocrinology

Date 2022 Nov 14

PMID 36372988

Authors

Angelique H Riepsamen

Mark W Donoghoe

Inthrani R Indran

Leah Hechtman

David M Robertson

Robert B Gilchrist

William L Ledger

Eu-Leong Yong

Affiliations

Soon will be listed here.

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.

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References

Wood J, Dumesic D, Abbott D, Strauss 3rd J . Molecular abnormalities in oocytes from women with polycystic ovary syndrome revealed by microarray analysis. J Clin Endocrinol Metab. 2006; 92(2):705-13. DOI: 10.1210/jc.2006-2123. View

Zhang Y, Yan Z, Qin Q, Nisenblat V, Chang H, Yu Y . Transcriptome Landscape of Human Folliculogenesis Reveals Oocyte and Granulosa Cell Interactions. Mol Cell. 2018; 72(6):1021-1034.e4. DOI: 10.1016/j.molcel.2018.10.029. View

Riepsamen A, Donoghoe M, Indran I, Hechtman L, Robertson D, Gilchrist R . Serum GDF9 and BMP15 as potential markers of ovarian function in women with and without polycystic ovary syndrome. Clin Endocrinol (Oxf). 2022; 98(4):567-577. PMC: 10952143. DOI: 10.1111/cen.14851. View

Luque-Ramirez M, Alpanes M, Sanchon R, Fernandez-Duran E, Ortiz-Flores A, Escobar-Morreale H . Referral bias in female functional hyperandrogenism and polycystic ovary syndrome. Eur J Endocrinol. 2015; 173(5):603-10. DOI: 10.1530/EJE-15-0646. View

Han X, McShane M, Sahertian R, White C, Ledger W . Pre-mixing serum samples with assay buffer is a prerequisite for reproducible anti-Mullerian hormone measurement using the Beckman Coulter Gen II assay. Hum Reprod. 2014; 29(5):1042-8. DOI: 10.1093/humrep/deu050. View

Hussein T, Thompson J, Gilchrist R . Oocyte-secreted factors enhance oocyte developmental competence. Dev Biol. 2006; 296(2):514-21. DOI: 10.1016/j.ydbio.2006.06.026. View

Li R, Zhang Q, Yang D, Li S, Lu S, Wu X . Prevalence of polycystic ovary syndrome in women in China: a large community-based study. Hum Reprod. 2013; 28(9):2562-9. DOI: 10.1093/humrep/det262. View

Lim A, Indran I, Kramer M, Yong E . Phenotypic spectrum of polycystic ovary syndrome and their relationship to the circadian biomarkers, melatonin and cortisol. Endocrinol Diabetes Metab. 2019; 2(3):e00047. PMC: 6613235. DOI: 10.1002/edm2.47. View

Dong J, Albertini D, Nishimori K, Kumar T, Lu N, Matzuk M . Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature. 1996; 383(6600):531-5. DOI: 10.1038/383531a0. View

10.

Teede H, Misso M, Costello M, Dokras A, Laven J, Moran L . Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod. 2018; 33(9):1602-1618. PMC: 6112576. DOI: 10.1093/humrep/dey256. View

11.

Zhu R, Lee B, Huang Z, Indran I, Li J, Shen L . Antimüllerian hormone, antral follicle count and ovarian volume predict menstrual cycle length in healthy women. Clin Endocrinol (Oxf). 2015; 84(6):870-7. DOI: 10.1111/cen.12984. View

12.

Virant-Klun I, Leicht S, Hughes C, Krijgsveld J . Identification of Maturation-Specific Proteins by Single-Cell Proteomics of Human Oocytes. Mol Cell Proteomics. 2016; 15(8):2616-27. PMC: 4974340. DOI: 10.1074/mcp.M115.056887. View

13.

de Resende L, Vireque A, Santana L, Moreno D, Japur de Sa Rosa E Silva A, Ferriani R . Single-cell expression analysis of BMP15 and GDF9 in mature oocytes and BMPR2 in cumulus cells of women with polycystic ovary syndrome undergoing controlled ovarian hyperstimulation. J Assist Reprod Genet. 2012; 29(10):1057-65. PMC: 3492567. DOI: 10.1007/s10815-012-9825-8. View

14.

Qiao J, Feng H . Extra- and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence. Hum Reprod Update. 2010; 17(1):17-33. PMC: 3001338. DOI: 10.1093/humupd/dmq032. View

15.

. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2003; 19(1):41-7. DOI: 10.1093/humrep/deh098. View

16.

Palomba S, Daolio J, La Sala G . Oocyte Competence in Women with Polycystic Ovary Syndrome. Trends Endocrinol Metab. 2016; 28(3):186-198. DOI: 10.1016/j.tem.2016.11.008. View

17.

Neubronner S, Indran I, Chan Y, Thu A, Yong E . Effect of body mass index (BMI) on phenotypic features of polycystic ovary syndrome (PCOS) in Singapore women: a prospective cross-sectional study. BMC Womens Health. 2021; 21(1):135. PMC: 8017849. DOI: 10.1186/s12905-021-01277-6. View

18.

Gong Y, Chin H, Lim L, Loy C, Obbard J, Yong E . Clustering of sex hormone disruptors in Singapore's marine environment. Environ Health Perspect. 2003; 111(12):1448-53. PMC: 1241645. DOI: 10.1289/ehp.6139. View

19.

Gilchrist R, Lane M, Thompson J . Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality. Hum Reprod Update. 2008; 14(2):159-77. DOI: 10.1093/humupd/dmm040. View

20.

Allen S, POTTER H, Azziz R . Prevalence of hyperandrogenemia among nonhirsute oligo-ovulatory women. Fertil Steril. 1997; 67(3):569-72. DOI: 10.1016/s0015-0282(97)80089-1. View