Abstract P167: Aging Exacerbates Increased MAP and Proteinuria in Male Rat Offspring of Hyperandrogenemic Mothers

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting 6-10 % of women, and is associated with hyperandrogenemia, oligo/anovulation and polycystic ovaries. Many women with PCOS have difficulty getting pregnant and, when they do, the infants are predisposed to preterm birth, metabolic disorders during childhood, and potential risk for the daughters to develop PCOS. The mechanisms by which the offspring of women with PCOS develop negative health outcomes are unknown. Our lab has already characterized the phenotype of young PCOS offspring showing an increased MAP and proteinuria in the males. In this study we tested the hypothesis that aging will exacerbate the negative health outcomes observed in the offspring of PCOS dams. Twelve months old female (F) and male (M) offspring of control (C) and PCOS (P) dams (SD; DHT 7.5mg/90d) were divided into 4 groups: F-C, F-P, M-C and M-P. At 12 months old, there is a significant decrease in body weight in F-P and M-P, compared to F-C and M-C, respectively (F-P: 284±4 vs. F-C: 301±5; M-P: 533±8 vs. M-C: 575±8 mg/24h, p<0.001) and the body weight remains lower until 18 months of age. Body composition analysis showed that there is a decrease in lean mass in F-P and M-P, compared to F-C and M-C, respectively (F-P: 284±4 vs. F-C: 301±5; M-P: 533±8 vs. M-C: 575±8 mg/24h, p<0.01). Proteinuria at 12 months, is higher in F-P and M-P, compared to F-C and M-C, respectively (F-P: 18±2 vs. F-C: 9±1; M-P: 169±8 vs. M-C: 108±6 mg/24h, p<0.001). This increased proteinuria is still observed at 15 months (F-P: 33±5 vs. F-C: 5±1; M-P: 143±7 vs. M-C: 103±4 mg/24h, p<0.001). Baseline mean arterial pressure (MAP, telemetry, 17 months old) was similar F-P vs. F-C (F-C: 109±2 mmHg vs. F-P: 107±1 mmHg; p=NS). However, in males, MAP was significantly higher in M-P than M-C (M-C: 114±1 mmHg vs. M-P: 127±1 mmHg; p<0.05). These results showed that aging exacerbates the increased MAP and proteinuria in males. Female offspring do not develop a PCOS phenotype with aging. Future studies will be necessary to determine the exact mechanisms responsible for the increase in blood pressure and renal injury.