Date of Award

2015

Degree Name

Biological Sciences

College

College of Science

Type of Degree

M.S.

Document Type

Thesis

First Advisor

Guo-Zhang Zhu

Second Advisor

Gary Schultz

Third Advisor

Marcia Harrison-Pitaniello

Abstract

In mammals, spermatogenesis is a biological process inside the testis to produce spermatozoa from spermatogonia. This process is governed by both genetic and epigenetic mechanisms and thus is a powerful system for epigenetic research. Methylation of histone 3 lysine 4 (H3K4) is an epigenetic mark, which has been found to be dynamically modulated in mouse male germ cells during spermatogenesis. Pax2 Transactivation domain Interaction Protein (PTIP) has been recently identified as part of a H3K4 methyltransferase complex. In this study, I hypothesize that PTIP is an essential epigenetic regulator in mouse spermatogenesis. To test this hypothesis, I first established a transgenic mouse model with conditional knockout of PTIP in postnatal male germ cells. Then I performed in vivo fertility assay, in vitro sperm assay, testis histology and Western blot. I found that PTIP conditional knockout males were as healthy as wild-type males, but they were infertile, had small testes, and did not produce sperm. In addition, our data demonstrated that H3K4 methylation was decreased in PTIP knockout testes. Taken together, our results validate my original hypothesis. Information collected from this study improves our understanding of male germ cell epigenome, offers novel insights into idiopathic infertility in men, and may provide new strategies for male contraception and assisted reproduction.

Subject(s)

Spermiogenesis in animals -- Research.

Male infertility -- Research.

Male contraception -- Research.