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CLONING, CHARACTERIZATION AND GENE REGULATION OF SODIUM HYDROGEN EXCHANGER DOMAIN CONTAINING PROTEIN-1 (NHEDC1) AND ROLE OF EPITHELIAL SODIUM CHANNEL ALPHA (ENaC a) IN SPERM CAPACITATION

Kumar, Priya Lava
http://rave.ohiolink.edu/etdc/view?acc_num=miami1416474059

Abstract Details

2014, Doctor of Philosophy, Miami University, Zoology.
In the mammalian sperm, regulation of intracellular pH (pHi) is essential for normal motility. Sodium hydrogen exchangers (NHEs) are integral membrane proteins that catalyze the electroneutral exchange of one extracellular Na+ for an intracellular H+ and are therefore important regulators of pHi. Of the several recognized NHE isoforms, NHE1, NHE5, NHE10 and the more recently identified NHEDC1 are known to be localized to the mature sperm flagellum. The focus of the first part of this dissertation is on NHEDC1, which was first partially characterized in humans. Subsequent studies in the mouse suggest that NHEDC1 is important for normal sperm motility and fertility. However, the characterization of NHEDC1 as a functional NHE has not been reported therefore the second chapter of this dissertation focuses on the gene cloning and functional characterization of the human orthologue of NHEDC1. Moreover, we demonstrate the existence of the rat orthologue of NHEDC1 and determine its and tissue distribution. Furthermore, since no studies have been done to determine the gene regulatory mechanisms of NHEDC1, the third chapter of this dissertation focuses on elucidating whether the epigenetic mechanism of DNA methylation plays a role in the regulation of NHEDC1 expression. The second part of this dissertation focuses on determining the role of ENaC a in sperm capacitation. Using the relatively non-specific inhibitors 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and amiloride to inhibit ENaC, previous studies have been interpreted to show that a decrease in Na+ permeability as a result of closure of ENaC is responsible for capacitation-associated hyperpolarization. However, these compounds can also inhibit other Na+ transporters in sperm. Therefore, using a mouse model with ENaC a alleles deleted only in the sperm we sought to categorically determine the role of ENaC a in sperm capacitation. Studying the role of Na+ ion transporters in sperm physiology is important as it may be possible to exploit them as targets for design of novel male factor contraceptive agents or for treatment of male infertility.
Paul James (Advisor)
108 p.
Biology; Molecular Biology; Physiology
Intracellular pH; sperm motility; sperm capacitation; DNA methylation; gene regulation; male infertility

Recommended Citations

Citations

  • Kumar, P. L. (2014). CLONING, CHARACTERIZATION AND GENE REGULATION OF SODIUM HYDROGEN EXCHANGER DOMAIN CONTAINING PROTEIN-1 (NHEDC1) AND ROLE OF EPITHELIAL SODIUM CHANNEL ALPHA (ENaC a) IN SPERM CAPACITATION [Doctoral dissertation, Miami University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=miami1416474059

    APA Style (7th edition)

  • Kumar, Priya. CLONING, CHARACTERIZATION AND GENE REGULATION OF SODIUM HYDROGEN EXCHANGER DOMAIN CONTAINING PROTEIN-1 (NHEDC1) AND ROLE OF EPITHELIAL SODIUM CHANNEL ALPHA (ENaC a) IN SPERM CAPACITATION . 2014. Miami University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=miami1416474059.

    MLA Style (8th edition)

  • Kumar, Priya. "CLONING, CHARACTERIZATION AND GENE REGULATION OF SODIUM HYDROGEN EXCHANGER DOMAIN CONTAINING PROTEIN-1 (NHEDC1) AND ROLE OF EPITHELIAL SODIUM CHANNEL ALPHA (ENaC a) IN SPERM CAPACITATION ." Doctoral dissertation, Miami University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=miami1416474059

    Chicago Manual of Style (17th edition)

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This open access ETD is published by Miami University and OhioLINK.