Essential roles and mechanisms of seipin in mouse reproduction
El Zowalaty, Ahmed Ezat
MetadataShow full item record
Reproduction is essential for the continuation of every species. During PhD, I studied reproductive biology and reproductive toxicology. The study of reproductive biology is essential to understand the mechanism of action of the male and female reproductive system at the molecular level to help physicians treat infertility. This dissertation also provides basic information essential to understand how some reproductive toxins work at the cellular and molecular levels to protect human/animals and the environment from the deleterious effects. The dissertation explained the molecular mechanism of seipin in male and female infertility using Bscl2-deficient mice. Bscl2 is required for adipocyte differentiation but its role in reproduction was not known. Bscl2 is highly and specifically expressed in round spermatids in the testis and deletion of Bscl2 led to impaired male fertility, DNA damage in spermatocytes and spermatids, fragmented chromocenter in round spermatids, and defective mitochondrial function in sperm leading to male infertility. These findings open new avenues to understand human infertility and treat infertile males. In addition, Bscl2-deficient female mice have defect during parturition and delivery of pups. The Bscl2-deficient females die during delivery, or fail to deliver pups on day of delivery and they have slightly longer gestation period. Bscl2 is highly expressed in the uterus and in the myometrium. Bscl2 is also essential for mammary gland development during lactation. Bscl2 is also highly and specifically expressed in mammary luminal epithelium cells, and Bscl2-deficient females fail to nurse their pups. Loss of Bscl2 leads to upregulation of cleaved caspase-3 and cell death in the mammary glands. There was upregulation of endoplasmic reticulum stress protein disulfide-isomerase (PDI), indicating that this mechanism potentially contributed to increased cell death and failure of lactation. In this dissertation, Bscl2 function in reproduction has been studied in the uterus, mammary gland and in the testis.