CHARACTERIZATION OF NOVEL TESTIS SPECIFIC ACTRT2 AND ACTRT3 IN MAMMALIAN SPERMATOGENESIS AND TOXICOLOGICAL PROFILE OF REMDESIVIR IN MALE FERTILITY OUTCOMES USING ANIMAL MODEL

Abstract

Spermatogenesis is a crucial process that generates fertile sperm, and it is a complex process that involves a remarkable number of proteins and molecules. However, the disruption of spermatogenesis at any stage can lead to infertility, which is a significant contributor to infertility in men. The prevalence of infertility is on the rise, and it is estimated that up to 15% of couples in American societies experience fertility issues, with approximately 50% of these cases being attributed to male infertility. The aim of this dissertation was to investigate genetic and environmental factors that impact male fertility. The focus was on two main areas, testis-toxic pharmaceuticals and actin-related proteins (ARPs). Chapter 2 evaluated the safety profile of the antiviral drug Remdesivir in mice through IP and IV exposure routes and determined its effects on spermatogenesis and fertility. This information will be valuable in understanding the off-target effects of pharmaceuticals and their impact on male fertility. Chapters 3 and 4 explored the role of ARPs in male fertility. Specifically, the focus was on two novel testis-specific ARPs, ACTRT2 and ACTRT3. These studies used genetically modified mouse models to investigate the reproductive effects of these novel ARP variations. These findings will provide new insights into the molecular mechanisms affecting male fertility and the role of actin-related proteins in the testis. In conclusion, this dissertation provides valuable information on the factors impacting male fertility. The results of this research may assist in the development of effective contraceptives and improve our understanding of the mechanisms involved in male infertility. These findings may help identify pathways that male infertility susceptible individuals can use to improve their ability to conceive and maintain reproductive health.