FRI151 Combined Maternal Hyperandrogenemia And Maternal Western Diet Consumption Programs Hypertension In Adult Female Offspring That Is Associated With Increased Leptin Levels
Authors: Shawky Noha M , Quin Ruth M , Davenport Kacey 
Published: October 2023

Disclosure: N.M. Shawky: None. R.M. Quin: None. K. Davenport: None. Funding: P20GM121334, AHA Career Development Award 938320

Background: Polycystic ovary syndrome (PCOS) is the major cause of hyperandrogenemia and the most common endocrinopathy in women of reproductive age. There is still a great controversy on whether daughters of PCOS women develop PCOS themselves. PCOS is commonly associated with increased blood pressure (BP) and obesity. We utilize a hyperandrogenemic female (HAF) rat model that develops a 3-fold increase in androgen levels to study the cardiometabolic consequences in the offspring (off.). We have previously shown that adult female off. of HAF rats consuming regular chow do not develop hypertension (HTN) or obesity. Consumption of western diet (WD) aggravates the reproductive phenotype of PCOS. We have shown that WD consumption also promotes further increase in BP, early onset obesity and hyperleptinemia in HAF rats, an effect that was not seen in normoandrogenemic controls. The current study was performed to test the hypothesis that WD consumption in HAFs (model of PCOS with worsened cardiometabolic phenotype) will program HTN, hyperandrogenemia and obesity in adult female off. Methods: At 4 wks of age, female Sprague Dawley (SD) rats were implanted with either 5α-dihydrotestosterone (7.5 mg, s.c.; HAF) or placebo (controls; CON) pellets, that were replaced every 85 days. HAF and CON rats were alsostarted on WD (high fat and high sucrose) or control diet (CD), thus forming 4 groups; CON-CD, CON-WD, HAF-CD and HAF-WD. At 10-13 wks of age, females were paired with SD males and allowed to get pregnant and lactate their off. At 16 wks of age, body composition (EchoMRI), plasma leptin (ELISA) and serum testosterone (T) [LC/MS] were determined in female off. (n=4-12). Another set of female off. were implanted with radiotelemetry transmitters to measure mean arterial pressure (MAP) [n=4-5]. All studies were done using 1 off./litter/group. Results: Despite the similar fat mass in all groups, plasma leptin was significantly higher in female off. from HAF-WD compared to female off. from CON-WD (1.5-fold, p&lt;0.05). Serum T was significantly higher (p&lt;0.05) in female off. from HAF-CD compared to female off. from CON-CD (4-fold), CON-WD (3-fold) and HAF-WD (3-fold). MAP was significantly higher in female off. from HAF-WD compared to female off. from CON-CD and HAF-CD (113 ± 3 vs 104 ± 2 and 103 ± 5 mmHg, p&lt;0.05). Yet, MAP was similar between female off. from CON-WD, CON-CD and HAF-WD. Conclusion: Our results indicate that independent mechanisms program hyperandrogenemia and HTN in adult female off. Combined maternal hyperandrogenemia and WD could program HTN in female off. that is associated with hyperleptinemia. This suggests that daughters of PCOS women with worsened cardiometabolic phenotype could be at risk of hyperleptinemia and HTN as adults. Our future studies will aim at addressing the role of hyperleptinemia in mediating HTN in the female off.

Presentation: Friday, June 16, 2023