Date of Completion

6-8-2020

Embargo Period

6-5-2020

Keywords

ovary, follicle, electron microscopy, 3D EM, TZPs

Major Advisor

Mark Terasaki

Associate Advisor

Laurinda Jaffe

Associate Advisor

Ann Cowan

Associate Advisor

Siu-Pok Yee

Associate Advisor

Kimberly Dodge-Kafka

Field of Study

Biomedical Science

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Throughout follicle development, oocytes and somatic granulosa cells depend on each other for proper development. Granulosa cells provide nutrients and other small molecules that govern the meiotic cycle of the oocyte. cGMP, produced by the natriuretic peptide receptor 2 (NPR2) in the granulosa cells, diffuses through gap junctions across the many cell layers of the follicle until it reaches the oocyte. High levels of cGMP in the oocyte keep it in meiotic arrest until luteinizing hormone, which binds to its receptor expressed on the outer-most granulosa cells, inactivates NPR2, causing cGMP levels to drop and meiosis to resume in the oocyte. Without proper communication of these cells, the oocyte does not develop properly and meiosis resumes spontaneously. Transzonal projections (TZPs) are thin cytoplasmic extensions sent by cumulus cells that traverse the zona pellucida and become the means for direct communication between the somatic cells and the oocyte. In this dissertation, we used large-volume three-dimensional electron microscopy to analyze TZPs in antral follicles. This study revealed the intricate network that TZPs make to connect with each other and with the oocyte. We also localized the LH receptor and NPR2 proteins in-vivo and provide new ideas for how these two proteins interact with each other across cells. Intercellular communication in the ovarian follicle is crucial for various functions that ultimately lead to a healthy fertilizable oocyte. Uncovering the mechanisms for this communication is vital for our understanding of human reproduction.

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