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DMRT1 promotes oogenesis by transcriptional activation of Stra8 in the mammalian fetal ovary.

ABSTRACT: Dmrt1 belongs to the DM domain gene family of conserved sexual regulators. In the mouse Dmrt1 is expressed in the genital ridge (the gonadal primordium) in both sexes and then becomes testis-specific shortly after sex determination. The essential role of DMRT1 in testicular differentiation is well established, and includes transcriptional repression of the meiotic inducer Stra8. However Dmrt1 mutant females are fertile and the role of Dmrt1 in the ovary has not been studied. Here we show in the mouse that most Dmrt1 mutant germ cells in the fetal ovary have greatly reduced expression of STRA8, and fail to properly localize SYCP3 and ?H2AX during meiotic prophase. Lack of DMRT1 in the fetal ovary results in the formation of many fewer primordial follicles in the juvenile ovary, although these are sufficient for fertility. Genome-wide chromatin immunoprecipitiation (ChIP-chip) and quantitative ChIP (qChIP) combined with mRNA expression profiling suggests that transcriptional activation of Stra8 in fetal germ cells is the main function of DMRT1 in females, and that this regulation likely is direct. Thus DMRT1 controls Stra8 sex-specifically, activating it in the fetal ovary and repressing it in the adult testis.

SUBMITTER: Krentz AD

PROVIDER: S-EPMC3131262 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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DMRT1 promotes oogenesis by transcriptional activation of Stra8 in the mammalian fetal ovary.

Krentz Anthony D AD Murphy Mark W MW Sarver Aaron L AL Griswold Michael D MD Bardwell Vivian J VJ Zarkower David D

Developmental biology 20110520 1

Dmrt1 belongs to the DM domain gene family of conserved sexual regulators. In the mouse Dmrt1 is expressed in the genital ridge (the gonadal primordium) in both sexes and then becomes testis-specific shortly after sex determination. The essential role of DMRT1 in testicular differentiation is well established, and includes transcriptional repression of the meiotic inducer Stra8. However Dmrt1 mutant females are fertile and the role of Dmrt1 in the ovary has not been studied. Here we show in the ...[more]

PMID: 21621532

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Project description:Ovarian follicular granulosa cells surround and nurture oocytes, and produce sex steroid hormones. It is believed that during development the ovarian surface epithelial cells invaginate into the ovary and develop into granulosa cells when associating with oogonia to form follicles. Using bovine fetal ovaries (n = 53) we identified a novel cell type, termed GREL for Gonadal Ridge Epithelial-Like. Using 25 markers for GREL and other cells we conducted immunohistochemistry and electron microscopy and chronologically tracked all somatic cell types during development. Before 70 days of gestation the gonadal ridge/ovarian primordium is formed by proliferation of GREL cells at the surface epithelium of the mesonephros. Primordial germ cells (PGCs) migrate into the ovarian primordium. After 70 days, stroma from the underlying mesonephros begins to penetrate the primordium, partitioning the developing ovary into irregularly-shaped ovigerous cords composed of GREL cells and PGCs/oogonia. Importantly we identified that the cords are separated from the stroma by a basal lamina. Around 130 days of gestation as the stroma expands laterally below the GREL cells on the surface thus establishing a sub-epithelial basal lamina and an epithelial-stromal interface, and it is at this stage that a mature surface epithelium develops from the GREL cells. The stroma continues to partition the ovigerous cords into smaller groups of cells eventually forming follicles containing an oogonium/oocyte surrounded by GREL cells, which become granulosa cells. Thus in contrast to the prevailing theory, the ovarian surface epithelial cells do not invaginate into the ovary to form the granulosa cells of follicles. Microarray analysis of gene expression was conducted on different cell types cultured from fetal ovaries to identify possible markers of somatic cells during development. Two different cell types: Gonadal Ridge Epithelial-Like cells (n=2, 130 days gestation) and adult fibroblasts (n=1) were cultured from digested bovine fetal ovaries and gene expression compared with each other by Bovine Genome Affy array analysis in Partek Genomics Suite software, to identify possible markers of somatic cells during development.

Dataset Information

DMRT1 promotes oogenesis by transcriptional activation of Stra8 in the mammalian fetal ovary.

Publications

DMRT1 promotes oogenesis by transcriptional activation of Stra8 in the mammalian fetal ovary.

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