GATA Like Protein-1: A Somatic Cell Factor Required for Normal Ovarian Development and Function

Date

2010-09-20

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Abstract

Oogenesis and follicular maturation are processes that require organized and precisely timed communication through paracrine and endocrine signals of neighboring tissues. Deviations in the cross talk between ovarian cells, or aberrant gene expression within one of the cell populations, can lead to germ cell loss and infertility in the adult female. Expression of Glp-1 in the somatic cells of the ovary is required for normal fertility in female mice, as a deficiency for Glp-1 leads to the absence of oocytes at birth and ovarian tubular formation in the adult. However, the nature of germ cell loss and tubular adenoma formation, in the setting of a somatic cell protein deficiency, is not well understood. In this report, I characterize the embryonic germ cell loss phenotype in Glp-1LacZ null mice. Immunohistochemical analyses of Glp-1LacZ null mouse ovaries show that germ cells are appropriately specified and migrate to the nascent gonad similarly to wild type. After their arrival at the gonad, precocious loss of the germ cells begins at or around E13.5. This loss is completed by birth and is accompanied by defects in the expression of oocyte-specific genes associated with meiotic entry. Interestingly, somatic pregranulosa cells retain their ability to secrete paracrine signaling molecules to the oocyte and are still able to form the basement membrane surrounding the germline cysts. In the adult, the structure of the germline cyst persists, albeit without germ cells, and there is loss of HPG axis communication. The loss in HPG communication in Glp-1LacZ null mice can be accounted for by loss of regulated steroidogenesis through the GATA4-dependent transcriptional activation of StAR. These data imply that the somatic cell protein Glp-1 regulates 1) germ cell survival early in embryogenesis and 2) steroidogenesis through StAR promoter activation.

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Embryo, Mammalian, Gene Expression Regulation, Developmental, Oogenesis, Germ Cell

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