Candidate Proteins that Regulate the Progression of Mammalian Oocyte Through Meiosis
Embargo until
2022-05-01
Date
2018-04-27
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Johns Hopkins University
Abstract
Mammalian oocytes in ovarian follicles are arrested at prophase of meiosis I. With each menstrual cycle, a few ovarian follicles respond to the surge of luteinizing hormone (LH) and the prophase I-arrested oocyte residing in these follicles resumes meiosis. This resumption of meiosis is known as oocyte maturation or meiotic maturation. Maturation failure can lead to female infertility and subfertility. The cause of maturation failure in human oocyte is still largely unknown. There are several proteins that have been illustrated to be important in different pathways regulating meiotic maturation. One part of this thesis explores the role of candidate regulatory protein AKAP13 from the A-kinase anchoring protein (AKAP) family in oocytes.
A-kinase anchoring proteins (AKAPs) are scaffolding proteins that bind to and regulate Protein Kinase A (PKA) activity. PKA activity is crucial for maintenance of prophase I arrest. AKAPs tether the regulatory subunit of PKA to different cellular structures, preventing diffusion of PKA away from its substrate. AKAP13 has been shown to be expressed in oocytes and granulosa cells by immunohistochemistry on ovarian tissue, and Akap13+/- female mice are subfertile. This thesis research shows that oocytes from Akap13 oocyte-specific, Zp3-Cre-driven conditional knockout (cKO) mice have normal morphology, and progress through meiotic maturation comparable to wild-type oocytes. No abnormality was detected in spindle organization or positioning at metaphase II, or in the rate of meiosis I completion in cKO oocytes. These results suggest that AKAP13 function in female reproduction may be more important in granulosa cells.
The second part of this thesis research builds on previous works in our lab showing the contribution of p21-activated kinase 4 (PAK4) to oocyte normal morphology and meiosis. Studies here assessed the relative expression levels of PAK protein family in prophase I-arrested oocyte. Understanding the expression levels of PAKs in the oocyte will help us to design better approaches to study the role of PAK proteins in oocyte health, morphology, and reproductive function.
Description
Keywords
Meiosis, reproductive function, meiotic maturation, oocyte maturation, infertility, subfertility, P21 activated kinase, Pak4, Protein Kinase A, PKA, A-kinase anchoring protein, AKAP13, spindle morphology, actin cap, prophase I arrest, asymmetric division, meiotic abnormality,