With aging, female rats exhibit a gradual loss of regular estrous cyclicity and decline in fertility (% of females with successful pregnancy) and fecundity (litter size). Our studies have provided evidence suggesting reproductive decline in aging female rats caused by pre-implantation failures and/or early post-implantation losses. Among the factors which influnce successful implantation during early gestation are the ovulation of healthy occytes, successful fertilization and development of these zygotes, and appropriate hormonal support for blastocyst development and implantation. This grant proposal outlines systematic approaches: 1) to examine the oocyte quality by assessing its cell viability, protein composition and fertilization rate in 4- to 14-month-old rats displaying regular estrous cyclicity, irregular estrous cyclicity, or persistent estrus (resulting from chronic anovulation); 2) to assess the cell viability and protein composition of developing embryos during Days 2-5 of pregnancy; 3) to examine the effects of aging and estrous cycle patterns on early embryonic development, and to determine the relation of plasma prolactin, progesterone and estradiol levels to blastocyst development and implantation success; 4) to determine the specific effects of estrous cycle patterns on reproductive function in aging female rats following experimental manipulations and a transient resumption of regular estrous cyclicity; 5) to examine the effects of progesterone-treatment early in life on subsequent oocyte quality, and on the patterns of embryonic development and hormone secretion during early pregnancy. The overall objective of this grant proposal is to understand the potential impact of ovarian and plasma progesterone and estradiol levels (as influenced by prolactin and gonadotropins) on folliculogenesis, oocyte and zygote quality, blastocyst development and implantation success in aging female rats displaying different estrous cycle patterns. We believe that the information gained from these proposed studies will provide important foundation for understanding the hormonal regulation of oocyte maturation, early embryogenesis, and blastocyst implantation in mammals. Such findings may be relevant to human reproduction, particularly for the in vitro fertilization and embryo transfer programs.
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