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Compromised Cumulus-Oocyte Complex Matrix Organization and Expansion in Women with PCOS

  • Infertility: Original Article
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Abstract

The cumulus-oocyte complex (COC) matrix plays a critical role in the ovulation and fertilization process and a major predictor of oocyte quality. Proteomics studies of follicular fluid showed differential expression of COC matrix proteins in women with polycystic ovary syndrome (PCOS), indicating altered COC matrix in these women. In the present study, we aimed to understand COC matrix gene induction in humans and its probable dysfunction in women with PCOS. Animal studies have shown that amphiregulin (AREG) and growth differentiation factor-9 (GDF-9) are important in the induction of COC matrix genes which are involved in cumulus expansion. The effects of AREG and GDF-9 on expression of tumor necrosis factor alpha induced protein 6 (TNFAIP6) and hyaluronan synthase 2 (HAS2) on human cumulus granulosa cells (CGCs) and murine COC expansion were evaluated. Further time-dependent effects of growth factor supplementation on these gene expressions in CGCs from PCOS and control women were compared. Follicular fluid from PCOS showed reduced COC matrix expansion capacity, using murine COCs. Expression of COC matrix genes TNFAIP6 and HAS2 were significantly reduced in CGCs of PCOS. Treatment of CGCs with AREG and GDF-9 together induced expression of both these genes in controls and could only restore HAS2 but not TNFAIP6 expression in PCOS. Our results suggest that the reduced potential of follicular fluid to support COC expansion, altered expression of structural constituents, and intrinsic defects in granulosa cells of women with PCOS may contribute to the aberrant COC organization and expansion in PCOS, thus affecting fertilization.

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Acknowledgements

The authors would like to thank all study participants, late Dr. Kusum Zaveri, Dr. Veena Bangera, Ms. Leena Mukadam, and Ms. Pushpa Dharwadkar (P.D. Hinduja National Hospital and Medical Research Centre, Mumbai) for collecting samples and providing data records of OPU. The authors appreciate Ms. Aditi Ambekar for her help in designing the study. The authors acknowledge NIRRH (RA/415/09-2016) and ICMR for providing necessary support. We would like to acknowledge the financial assistance provided by CSIR, Government of India, to KP for pursuing her doctoral studies.

Funding

This study was partially funded by the Department of Biotechnology (DBT), Government of India (BT/PR10574/MED/12/394/2008).

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Authors and Affiliations

  1. Department of Molecular Endocrinology, National Institute for Research in Reproductive Health, Indian Council of Medical Research, Mumbai, 400012, India

    Krutika Patil, Gayatri Shinde & Srabani Mukherjee

  2. P.D, Hinduja National Hospital and Medical Research Centre, Mumbai, 400004, India

    Indira Hinduja

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  1. Krutika Patil
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Contributions

SM: concept and design, interpretation of the data, and final approval for manuscript submission. KP: design and completion of the experiments, analysis of the results, and drafting of the manuscript. GS: carried out animal experiments. IH: provided clinical samples and approved the final version of the manuscript.

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Correspondence to Srabani Mukherjee.

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This study has been approved by Institutional Ethics Committee and written informed consents were obtained from all study participants. This study was also approved by Animal Ethics Committee of the institute. All animal experiments were in accordance with institutional ethics committee guides. Ethics approval number is 139/2007.

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Patil, K., Shinde, G., Hinduja, I. et al. Compromised Cumulus-Oocyte Complex Matrix Organization and Expansion in Women with PCOS. Reprod. Sci. 29, 836–848 (2022). https://doi.org/10.1007/s43032-021-00775-0

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