OR04-04 Sexually Dimorphic Impact Of Gestational Hyperandrogenism On Offspring Growth Trajectory

Disclosure: E. Topaktas: None. A.B. Ghnenis: None. J.N. Ciarelli: None. S. Domke: None. V. Padmanabhan: None. A.K. Vyas: None. Gestational hyperandrogenism, as seen in polycystic ovary syndrome, adversely programs birth weight and small for gestational babies. In our established sheep model of PCOS phenotype, gestational testosterone (T) excess from days 30-90 of gestation (sexually dimorphic window where male fetuses naturally are exposed to elevated T) had no effect on fetal weight in early and mid-gestation (day 65 and 90; term 147 days) but manifested in intrauterine growth restriction (IUGR) on day 140 gestation followed by catch up growth in the early postnatal period in female lambs. The impact of T excess on IUGR and postnatal catch up seen in female may not be seen in the male due the elevated T it is naturally exposed to. We hypothesized that gestational T excess will have sexually dimorphic impact on late gestational fetal weights, a period of maximal fetal growth and the postnatal growth trajectory. Pregnant ewes were injected with T propionate (T), or oil-vehicle (CON), 100 mg I.M. twice weekly from gestational day 30 to 90 to obtain CON female (CF), T females (TF), CON males (CM), and T males (TM) fetuses on day 120 of gestation(GD120). In a the follow up study, lambs were delivered and weekly weights from CF, TF, CM, and TM were obtained till early adulthood. GD120 data and neonatal cytokine profile was analyzed by 2-way ANOVA and Cohen D (d) analysis while the postnatal growth data was subjected to mixed model ANOVA. T fetuses at GD120 weighed less then CON (P<0.05); prenatal T excess reduced body weight (BW in kg) in both sexes compared to CON (CM 3.38±0.15 vs.TM 2.68±0.14, p=0.001; CF 3.27±0.21 vs.TF 2.72±0.11, p=0.03). There was a large magnitude increase in IL4 (d=0.92) and moderate in IL6 (d=0.78), IL1α (d=0.74), TNFα (d=0.77) and MIPβ (d=0.74) in TF compared to CF. TF also has large magnitude increase in MIPβ (d=0.97) and moderate magnitude increase in IL36RA (d=0.78), IL6 (d=0.70) compared to TM. TM has large magnitude increase in MIPβ (d=0.99) and IL6 (d=0.80) compared to CM. In contrast, during postnatal life, a significant age x treatment interaction (p =0.029) in average weight gain over time was evident. Growth was significantly higher in CM, TM and TF than CF and did not differ between CM and TM. Presence of IUGR in both sexes in late gestation, as opposed to catchup growth in the postnatal period only in TF not TM could have implication in sex-specific impact on the cardiometabolic function in the lambs. Supported by NIH R01HL139639. Presentation: Thursday, June 15, 2023