Microscopic and Macroscopic Investigations of Male Development Anatomy and Fertility, and the Role of Y Chromosome Genes

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2016-08
Authors
Ruthig, Victor
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[Honolulu] : [University of Hawaii at Manoa], [August 2016]
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There have been decades of work on the Y chromosome and how it relates to maleness and male reproduction. In light of the increasing decline of human male fertility and dependence on assisted reproduction more knowledge about the causes behind male infertility is needed to find more solutions for affected men. This dissertation details histological investigations aiming to elucidate function of Y chromosome genes in male development and fertility using a mouse model. The testis and the seminiferous tubules within were explored and spermatogenesis was quantitatively assessed. Males lacking Y chromosome and transgenic for either the key Y-derived transgenes (Sry and Eif2s3y) or transgenes of their non Y-derived homologues (Sox9 and Eif2s3x) were shown to produce haploid germ cells that could be used for assisted reproduction technologies (ART) and yield live offspring. Another Y chromosome gene, Zfy2, was identified as a gene allowing for transformation of round spermatids into sperm. While in males with only two Y chromosome genes, Sry and Eif2s3y, spermatogenesis progressed to round spermatid stage, addition of Zfy2 allowed for complete spermatogenesis and formation of sperm capable of generating offspring with ART. Investigations into the testicular abnormalities in mice with limited Y chromosome gene contribution showed relationship between the number of Y genes present and the severity and distribution of cellular abnormalities in the seminiferous epithelium and defects of the testis interstitium. Human spermatogenesis was also histologically investigated utilizing testis biopsies from normal and infertile men, some with Y chromosome azoospermic factor (AZF) deletions, validating mice with Y chromosome deficiencies as a model for human male Y-linked infertility. Gross anatomy investigations into human male urogenital anatomy were also undertaken using a novel dissection method in order to grow the repository of male urogenital teaching tools at the medical school. Both examined specimens had common male genital pathologies (direct inguinal hernia, varicocele) and so also showcase physical abnormalities that can affect male reproductive health.
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Ph.D. University of Hawaii at Manoa 2016.
Includes bibliographical references.
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Y chromosome, spermatogenesis, male development, male fertility, male anatomy, testis histology
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Theses for the degree of Doctor of Philosophy (University of Hawaii at Manoa). Anatomy, Biochemistry & Physiology
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