The effects of prenatal androgen exposure on cardiac function and tolerance to ischemia/reperfusion injury in male and female rats during adulthood

Abstract

Aims: Cardiovascular diseases may originate from suboptimal intrauterine environments. We aimed to examine the effects of prenatal androgen exposure (PAE) on heart basal hemodynamic parameters and tolerance to ischemia/reperfusion (I/R) injury, in PAE adult females and males.

Main methods: Pregnant Wistar rats in the experimental group (n = 8) received 5 mg of testosterone (s.c. injection) on the 20th day of pregnancy, while controls received solvent. The hearts of adult female and male offspring were isolated and perfused in a Langendorff apparatus, values of left ventricular systolic pressure(LVSP), left ventricular developed pressure(LVDP), rate pressure product(RPP) and peak rates of positive and negative changes in left ventricular pressure(±dp/dt) were recorded using a power lab system.

Key findings: At baseline, PAE adult males demonstrated significant higher values of LVSP, LVDP, RPP and ± dp/dt, compared to controls and PAE adult females (p < 0.05), while PAE adult females showed no significant differences compared to controls. In PAE adult males, LVSP, LVDP, RPP and ± dp/dt had significant decreasing trends per phases after I/R, compared to their controls and PAE females, while these decreasing trends were not statistically significant in PAE adult female rats vs. their controls.

Significance: The impact of prenatal androgen exposure on adulthood cardiac function and tolerance to I/R is gender dependent, which may be partly explained by different cardiac effects of hyperandrogenism in males versus females. After prenatal androgen exposure, the baseline hemodynamic parameters of the hearts of adult males are increased; although they had less tolerance to I/R, findings however not observed in females.

Keywords: Cardiac function; Fetal life; Ischemia/reperfusion injury; Rat; Testosterone.