Insulin resistance and depressed cardiac G6PD activity induced by glucocorticoid exposure during pregnancy are attenuated by maternal estrogen-progestin therapy

Abstract

This study aimed to investigate the effects of maternal combined oral contraceptive (COC) on dams that were exposed to late gestational glucocorticoids (GC). Twenty-four pregnant female rats were randomly allotted into 4 groups of 6 dams each. Dams received COC (combination of 1.0 μg ethinylestradiol and 5.0 μg levonorgestrel p.o.) between 3rd and 11th week after delivery with or without prior exposure to GC (dexamethasone; 0.2 mg/kg p.o.) that was administered between gestational days 14-19. Data showed that late-gestational GC exposure led to insulin resistance (IR), increased cardiac adenosine deaminase (ADA), xanthine oxidase (XO), lactate, lactate dehydrogenase (LDH), and disrupted cardiac glucose-6-phosphate dehydrogenase (G6PD)-dependent antioxidant defenses. On the other hand, maternal COC treatment in dams not exposed to gestational GC led to IR, increased cardiac XO, LDH and defective cardiac G6PD-dependent antioxidant defenses. However, maternal COC with prior gestational GC exposure led to attenuated IR, cardiac ADA, UA, LDH, and improved cardiac G6PD-dependent antioxidant defenses but worsened cardiac triglyceride (TG) accumulation when compared with dam with gestational GC exposure without maternal COC. Taken together, the findings of this study provide evidence that maternal COC treatment improves late gestational GC-programmed effects. This is however accompanied with enhanced cardiac TG accumulation.