Turner syndrome (TS) is a genetic condition affecting one in 2,500 newborn girls, resulting from missing the second X chromosome or parts thereof (referred to as “45,X” or “XO”). TS impairs multiple organ systems. Infertility is one of the most common symptoms in TS women, owing to ovarian failure, low ovarian reserve, and poor oocytes quality. Little is known about the biological mechanisms underlying TS infertility, specifically when and how ovary dysfunction begins. This makes it difficult to predict and preserve fertility in women with TS. We have engineered a rat model of TS which is the first animal model to recapitulate ovarian dysfunction seen in women with TS. We deleted the sex determining SRY gene locus by CRISPR, generating XY female rats. When mated with XY male rats, the female progenies are XX, XO, XY, or XXY. Of three XO rats set up for mating, to date, no live litters have been obtained, therefore indicating infertility. XO rat ovary histology revealed a) smaller and fewer antral follicles, b) fewer primordial follicles, c) enlarged oocytes of primary and secondary follicles and d) present corpora lutea. Altogether, this suggests that XO rats exhibits reproductive dysfunction similar to those seen in women with TS. We will investigate the biological mechanisms of TS infertility using our rat XO model. We will study the developmental origins of reduced fertility as a consequence of X chromosome loss by determining the altered methylomes, transcriptomes, and ovarian reproductive phenotypes. This will identify dosage sensitive X chromosome genes which contribute to infertility. Moreover, we will determine the developmental stages of specific ovarian dysfunction, experiments not possible in XO humans. Furthermore, in parallel experiments, we are using the XO model to investigate the developmental origins of cognitive deficits in TS using, integrating -omic approaches and cognitive testing.