A Nuclear and Cytoplasmic Characterization of Bovine Oocytes Reveals That Cysteamine Partially Rescues the Embryo Development in a Model of Low Ovarian Reserve

Decreased oocyte quality is a major determinant of age-associated fertility decline. Similarly, individuals affected by early ovarian aging carry low-quality oocytes. Using an established bovine model of early ovarian aging, we investigated key features of ‘quality’ oocyte maturation, associated with the onset of egg aneuploidy and reproductive aging, such as histone modifications, mitochondria distribution and activity, reduced glutathione (GSH) content, and gap junction functionality. Bovine ovaries were classified according to the antral follicle count (AFC), and the retrieved oocytes were processed immediately or matured in vitro. We observed alterations in several cellular processes, suggesting a multifactorial etiology of the reduced oocyte quality. Furthermore, we performed a rescue experiment for one of the parameters considered. By adding cysteamine to the maturation medium, we experimentally increased the free radical scavenger ability of the ‘low competence’ oocytes and obtained a higher embryo development. Our findings show that adopting culture conditions that counteract the free radicals has a positive impact on the quality of ‘compromised’ oocytes. Specifically, cysteamine treatment seems to be a promising option for treating aging-related deficiencies in embryo development. Simple Summary Women’s reproductive performance starts declining in the mid-30s, and by age 40–45, the possibility of becoming pregnant becomes very small. Reproductive aging is a physiological process of fertility decline characterized by a decrease in quality and stockpile of eggs (also called ovarian reserve) in most mammals. However, young individuals too can show an accelerated reproductive aging that similarly results in a low ovarian reserve and hypofertility. This syndrome, called premature ovarian failure (POF), is becoming a relevant problem due to the general tendency to postpone the first pregnancy. In this study, we used bovine ovaries that were classified in two categories, according to the number of follicles visible on the ovarian surface, and analyzed some parameters of egg maturation. We observed that eggs from the ‘aging-like’ ovaries carry several defects that impair maturation. However, one of the parameters was improved upon supplementation with a scavenger of free radicals, providing a proof of concept that in-depth knowledge of the cellular mechanisms is essential to find solutions to everyday-life problems.