Cellular Processes in Human Ovarian Follicles Are Regulated by Expression Profile of New Gene Markers-Clinical Approach.

Błażej Chermuła,Bogusława Stelmach,Robert Zygmunt Spaczyński,Wiesława Kranc,Hanna Piotrowska-Kempisty,Paul Mozdziak,Bartosz Kempisty,Leszek Pawelczyk,Piotr Celichowski

doi:10.3390/jcm11010073

Abstract

In the growing ovarian follicle, the maturing oocyte is accompanied by cumulus (CCs) and granulosa (GCs) cells. Currently, there remain many unanswered questions about the epithelial origin of these cells. Global and targeted gene transcript levels were assessed on 1, 7, 15, 30 days of culture for CCs and GCs. Detailed analysis of the genes belonging to epithelial cell-associated ontological groups allowed us to assess a total of 168 genes expressed in CCs (97 genes) and GCs (71 genes) during long-term in vitro culture. Expression changes of the analyzed genes allowed the identification of the group of genes: TGFBR3, PTGS2, PRKX, AHI1, and IL11, whose expression decreased the most and the group of ANXA3, DKK1, CCND1, STC1, CAV1, and SFRP4 genes, whose expression significantly increased. These genes’ expression indicates CCs and GCs epithelialization processes and their epithelial origin. Expression change analysis of genes involved in epithelization processes in GCs and CCs during their in vitro culture made it possible to describe the most significantly altered of the 11 genes. Detailed analysis of gene expression in these two cell populations at different time intervals confirms their ovarian surface epithelial origin. Furthermore, some gene expression profiles appear to have tumorigenic properties, suggesting that granulosa cells may play a role in cancerogenesis.

Highlights

The outer part of the ovary is covered by germinal epithelium and somatic granulosa cells, which are modified throughout the ovarian follicular formation process [1,2]
Human ovarian granulosa and cumulus cells long-term in vitro culture and gene expression analysis allowed us to study, on a large scale, a wide group of 168 genes belonging to ontological groups characterizing epithelial cell physiological processes
The dynamic changes in gene expression were investigated by the transcriptomic profile on the 1st, 7th, 15th, and 30th day of human CC and GC cultures

Summary

Introduction

The outer part of the ovary is covered by germinal epithelium and somatic granulosa cells, which are modified throughout the ovarian follicular formation process [1,2] These cells form a direct barrier between the oocyte and the surrounding external environment, creating the proper conditions necessary for oocyte growth and maturation [3]. As well as granulosa proliferation and differentiation, are mainly regulated by BMP15 (bone morphogenetic protein 15) and GDF9 (growth differentiation factor 9) Other regulators of these processes are paracrine factors, such as AMH (anti-Mullerian hormone), inhibin, activins, and TGFα (transforming growth factor-alpha), which are produced by the somatic cells surrounding oocytes [5]. An increase of granulosa cell FSH (follicle-stimulating hormone) and IGF1 (insulin-like growth factor 1)

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