Abstract
Catechol-O-methyltransferase (COMT) has been shown to be a key regulator of pregnancy outcomes in mouse, and its deficiency is causative in the development of a preeclampsia-like disease process. Preeclampsia is a human pregnancy disorder associated with failure of intrauterine trophoblast cell invasion and trophoblast-guided uterine spiral artery remodeling, which are not well-developed in mouse. The purpose of this study was to investigate COMT in rat, a species with deep intrauterine trophoblast invasion. To accomplish this task, we used clustered regularly interspaced short palindromic repeats/Cas9-mediated genome editing of the rat Comt gene. A Comt null rat model was established and its fertility characterized. Comt null male and female rats were viable and fertile. COMT deficiency did not significantly impact pregnancy outcomes, including litter size, placental and fetal weights, Mendelian and sex ratios, or pregnancy-dependent adaptations to hypoxia. Collectively, our findings indicate that pregnancy-associated phenotypic outcomes of COMT deficiency are not equivalent in mouse and rat. In rat, COMT is not required for a successful pregnancy outcome.