Title

The role of steroids in the regulation of oocyte cyst breakdown and primordial follicle assembly in the neonatal mouse ovary

Author

Ying Chen

Date of Award

2008

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

Advisor(s)

Melissa E. Pepling

Keywords

Steroids, Oocyte cyst breakdown, Primordial follicle assembly, Ovary

Subject Categories

Biology

Abstract

Mouse germ cells develop in special structures called germline cysts formed by several rounds of mitosis and incomplete cytokinesis. Right after birth, cysts break down and each individual germ cell becomes enclosed in a primordial follicle, which represents the total germ cell population a female has throughout her reproductive life. At the same time, about two thirds of the germ cells die with only one third surviving. The mechanisms regulating cyst breakdown and selective oocyte loss are not completely understood. A more detailed understanding of these processes will give us more insights into normal early oocyte development and female fertility problems.

In this study, utilizing the ovary organ culture system, the role of hormone signaling on cyst breakdown is investigated. Estrogen, progesterone, as well as phytoestrogen genistein all displayed an inhibitory effect on cyst breakdown, causing large cysts to persist during culture. Primordial follicle assembly is also inhibited. Ovaries cultured in vitro cut off from their maternal estrogen supply from the mother, undergo premature cyst breakdown, oocyte death and follicle development. Adding estradiol or progesterone back to the culture media rescues this premature development. Using estrogen receptor specific agonists and antagonists, we established that both estrogen receptor a and estrogen receptor β, as well as a membrane estrogen receptor, are involved in estrogen signaling in the neonatal ovary. ICI182,780, a pure antiestrogen, can reverse the effect of estradiol on cyst breakdown. Our current working model is that before birth, the fetus is exposed to estrogen from the mother, and the relatively high estrogen level inhibits the cysts from breaking down; Right after birth, estrogen levels drop dramatically, and this triggers some oocytes to die and the cysts to break down into individual oocytes.

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