Differentiation of human embryonic stem cells into granulosa cells: potential application in polycystic ovary syndrome and investigation of genetic mechanisms
Date Issued
2014
Date
2014
Author(s)
Lan, Chen-Wei
Abstract
Ovarian granulosa cells are important for the development of oocytes. Recent studies have suggested that the dysfunction of granulosa cells may lead to disorders of ovarian function, such as polycystic ovary syndrome (PCOS).
Human embryonic stem cells (hESCs) have an unlimited capacity and can differentiate into all cell types. Through multi-step approaches comprising in vitro treatments with cocktails of growth factors, gene expression analyse the progress of hESCs to primitive streak–mesendoderm, intermediate plate mesoderm, and finally to functional granulosa-like cells that expressed the granulosa cell-specific forkhead transcription factor FOXL2, CYP19A1, anti-Müllerian hormone, the type 2 AMH receptor, and the follicle stimulating hormone receptor. The granulosa cells are capable of producing AMH and aromatizing testosterone to estradiol. This developmental system will provide a model to elucidate granulosa cell development.
In order to understand PCOS disease on the granulosa cells, we use cDNA microarray technology to compare differential gene expressions in granulosa cells: including 6 women with normal ovulatory and 6 with PCOS. A total of 243 genes were showed to have differential expressions in the PCOS granulosa cells when compared with normal. These differentially expressed genes are involved in reproductive system development and involved in the mitogen-activated protein kinase/ extracellular regulated kinase (MAPK/ERK) signaling pathways. Western blot analyses confirmed that MAP3K4 and phospho-ERK1/2 was decreased in PCOS granulosa cells. The molecular mechanisms will help us to understand the pathogenesis for PCOS disease.
Subjects
人類胚胎幹細胞
卵巢顆粒細胞
濾泡生成
抗穆氏管荷爾蒙
多囊性卵巢症候群
MAPK/ERK訊號傳遞路徑
SDGs
Type
thesis
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