Rehma Saeed
Pronouns: She/Her
Research Mentor(s): Vasantha Padmanabhan
Research Mentor School/College/Department: Pediatrics / Medicine
Program: UROPF
Session: Session 6 (3:40pm – 4:30pm)
Authors: Rehma Saeed, Vasantha Padmanabhan, Nadia Saadat
Abstract
Excess exposure to testosterone during pregnancy can lead to a multitude of metabolic and reproductive changes due to a change in the steroid levels within both the pregnant mother and the fetus (1). Since the Padmanabhan lab has previously established a prenatal-T phenotype in which the effect of excess testosterone on the metabolic environment has been investigated through insulin, glucose, and progesterone levels, the effect of excess testosterone on steroid levels is yet another mechanism that could contribute to maternal adverse health outcomes (2). Insulin, glucose, and progesterone are all vital in the growth and development of fetuses; however, exposure to testosterone led to intrauterine growth restriction (IUGR) in the phenotype, leading to smaller fetuses (2). Steroidogenesis includes the production of cholesterol leading to either gonadal steroids known as hormones or adrenal steroids known as corticosteroids that arise as a result of enzymatic transformations (3). Testosterone is a steroid involved in both the gonadal and the adrenal pathway. As such, excess testosterone has the potential to influence the steroidogenesis of gonadal steroids such as 17-OH Pregnenolone, 17-OH Alllopregnenolone, Progesterone, 16-OH Progesterone, 17-OH Progesterone, Pregnenolone, Allopregnanolone, DHEA, Testosterone, Androstenedione, Androstenediol, Androsterone as well as adrenal steroids such as 18-Hydroxycortisol, 11-OH Androstendione, 11-Deoxycortisol, 11-DOC, Cortisone, Cortisol and Corticosterone. It is predicted that excess testosterone exposure will lead to a decrease in both the gonadal and adrenal pathways due to the negative feedback mechanisms, meaning increased testosterone would signal that further steroidogenesis would not be necessary. To study the mechanisms involved in the adverse effects of maternal and fetal health after excess testosterone exposure during pregnancy, an animal model with high translational relevance was used. Specifically, a sheep model was used as previous studies have provided support for the idea that sheep are an effective model for humans, especially during pregnancy, as the development of lamb fetuses is most similar to human fetuses as lambs similarly spend a prolonged period in gestation (4). As such, the Padmanabhan lab has successfully based the previously described prenatal-T phenotype using a sheep model (2). A total of 17 pregnant sheep were the subjects of this study. 12 of the sheep were a part of the experimental group and 5 sheep were in the control group. The experimental group was injected intramuscularly from day 30 to day 90 of the 147-day gestation period with 100mg of T-propionate in 2 mL of corn oil. While the control group was injected intramuscularly from day 30 to day 90 of 147-day gestation period with 2 mL of corn oil. Following the treatment, plasma samples were collected during pregnancy on day 127.125.32 of gestation on 03/18/2021 prior to comprehensive steroid panel collection using LC-MS/MS. The data from the comprehensive steroid panel first underwent the Shapiro-Wilk normality test in order to remove any outliers. Next, T-Tests were performed to compare the mean value of the control group and the experimental group in order to determine if the excess testosterone led to significant differences between both groups. Finally, bar graphs were generated with 2SEM error bars as a way to verify significance determined by the T-Tests.
