Proteomic Alterations in Follicular Fluid of Human Small Antral Follicles Collected from Polycystic Ovaries-A Pilot Study.

Indira Pla,Roger Appelqvist,Claus Yding Andersen,György Marko-Varga,K Barbara Sahlin,Johan Malm,Susanne Elisabeth Pors,Stine Gry Kristensen,Aniel Sanchez

doi:10.3390/life12030391

Abstract

Polycystic ovaries (PCO) contain antral follicles that arrest growing around 3–11 mm in diameter, perturbing the dominant follicle’s selection and the subsequent ovulatory process. Proteomic alterations of PCO follicular fluid (FF) (i.e., microenvironment in which the oocyte develops until ovulation) have been studied from large follicles in connection with oocyte pickup during ovarian stimulation. The present study aimed to detect proteomic alterations in FF from unstimulated human small antral follicles (hSAF) obtained from PCO. After performing deep-sequencing label-free proteomics on 10 PCO and 10 non-PCO FF samples from unstimulated hSAF (4.6–9.8 mm), 1436 proteins were identified, of which 115 were dysregulated in PCO FF samples. Pathways and processes related to the immune system, inflammation, and oxidative stress appeared to be upregulated in PCO, while extracellular matrix receptors interactions, the collagens-containing extracellular matrix, and the regulation of signaling were downregulated. The secreted proteins SFRP1, THBS4, and C1QC significantly decreased their expression in PCO FF, and this downregulation was suggested to affect future oocyte competence. In conclusion, our study revealed, for the first time, evidence of proteomic alterations occurring in the FF of PCO hSAF that may be related to the dysfunction of follicular growth and subsequent oocyte competence.

Highlights

Folliculogenesis is impaired, and follicles arrest prematurely when antral follicles reach a diameter of around 3–11 mm [2]. This phenomenon has been associated with the augmented production of androgen by theca cells, which is believed to be provoked by hormonal dysregulation, which includes an increase in gonadotropin-releasing hormone (GnRH) pulses that favor the upregulation of LH [3]
From the 38 proteins uniquely quantified in polycystic ovary (PCO) samples, thioredoxin reductase 1 (TXNRD1)
This work is, to our knowledge, the first high-throughput proteomic study performed on follicular fluid (FF) from unstimulated human small antral follicles (hSAF) (4.6–9.8 mm) of polycystic ovaries

Summary

Introduction

Polycystic ovary syndrome (PCOS) is one of the most common causes of female infertility, with a prevalence rate between 5 and 10% [1]. A polycystic ovary (PCO) is characterized by an increased number of small antral follicles (SAF) compared with normal ovaries. Folliculogenesis is impaired, and follicles arrest prematurely when antral follicles reach a diameter of around 3–11 mm [2]. This phenomenon has been associated with the augmented production of androgen by theca cells, which is believed to be provoked by hormonal dysregulation, which includes an increase in gonadotropin-releasing hormone (GnRH) pulses that favor the upregulation of LH [3]. Many studies have been carried out to understand the pathophysiology and molecular aspects of this disorder, specific causes of aberrant follicular development and the cessation of dominant follicle selection remain unclear

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Conclusion