The role of T cells on the elevated blood pressure of female and male PCOS offspring

Abstract

Prenatal factors may program the immune response in offspring of women with polycystic ovary syndrome (PCOS) and contribute to their elevated cardiovascular and renal risk. For example, PCOS women might have altered T cell concentrations which could adversely affect their offspring; however, whether adult PCOS offspring have an increase in T cells remains undetermined. We hypothesize that T cells contribute to the increase in blood pressure and proteinuria in both male and female offspring from hyperandrogenemic female (HAF) rats. Female (f) and male (m) HAF offspring (HAF‐off) and placebo offspring (Pla‐off), 24 weeks old, from HAF dams (DHT pellet 7.5mg/90d starting at 4 wks of age) or placebo dams (placebo pellet/90d) were divided into 4 groups (n=4/grp): fPla‐off, fHAF‐off, mPla‐off, mHAF‐off, respectively. We measured fat mass and lean mass by ECHO MRI, body weight, proteinuria (24h urine), and mean arterial pressure (MAP) by telemetry. We also examined the circulating and intrarenal T regulatory (CD4+CD25+FOXP3+) or Th17 effector cells (CD4+CD25‐RORγ+) by flow cytometry. MAP and proteinuria were significantly higher in male and female HAF‐off than Pla‐off (mPCOS: 121±2 mmHg vs. mPla: 112±1 mmHg; p<0.05; fPCOS: 117±3 vs. fPla‐off: 109±2; p<0.05) (proteinuria: fPla‐off: 4.1±1 mg/24h vs. fHAF‐off: 9.4±1.7 mg/24h; p<0.05; mPla‐off: 20±2.2 mg/24h vs. mHAF: 43.7±6 mg/24h; p<0.05). Female and male pups of HAF dams have similar body weights as pups of control dams. However, males of HAF dams have greater body fat mass and less lean mass, than do males of control dams (mHAF‐off: 29.57±1.07 g vs. mPla‐off: 25.95±1.33 g; p<0.05, and mHAF‐off: 381.4±4.9 g vs. mPla‐off: 366.3±4.1 g; p<0.05, respectively). Females of HAF dams have similar fat mass but less lean mass than do control female offspring (LM: fPla‐off: 223.3±2.5 g vs. fHAF‐off: 214.9±2.0 g; p<0.05). Contrary to our hypothesis we did not find differences in circulating or intrarenal T cells between fPla‐off and fHAF‐off or mPla‐off and mHAF‐off. The exposure to hyperandrogenemia in utero life may not increases the T cells in PCOS offspring later in life and is not responsible for the increased BP. However, further preclinical studies are necessary to determine the role of the immune response and the possible mechanisms responsible for the increase in blood pressure and renal injury in PCOS offspring.Support or Funding InformationSupported by AHA14POST18640015 (ROM) and P20GM121334 (ROM and JFR).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.