Effects of dexamethasone on luteal steroidogenesis, cell apoptosis and PKA/CREB/PPARG pathway in rats

This study aimed to investigate effects of dexamethasone (Dex) on luteal steroidogenesis, cell apoptosis and PKA/CREB/PPARG pathway in rats. Rats aged 28 days were treated with PMSG and hCG to obtain amounts of corpora lutea, followed by injections of Dex (Dex group) or saline (Control, Con group) for 7 days. Serum was collected to detect biochemical indices with corresponding kits and progesterone (P4) levels by RIA. Ovaries were collected for HE, IHC and TUNEL analysis, and genes and proteins associated with steroidogenesis and apoptosis, including PKA/CREB/PPARG members using real-time PCR and western blotting, respectively. Results showed that Dex treatment increased serum triglyceride and glucose levels (P < 0.05), and decreased high－density lipoprotein cholesterol and low－density lipoprotein cholesterol levels (P < 0.05). Dex treatment increased serum P4 level (P < 0.05), as well as ovarian mRNA abundances of Star and Cyp11a1 (P < 0.05), and protein levels of StAR and HSD3B (P < 0.05); Dex also increased the Bax/Bcl-2 ratio at both mRNA and protein levels (P < 0.05), with a greater incidence of apoptosis confirmed by BAX immunostaining and TUNEL assay. Dex treatment increased the mRNA abundances and protein levels of PKA/CREB/PPARG members (P < 0.05). IHC analysis showed that PPARG was localized in the nuclei as well as cytoplasm of luteal cells. Overall, Dex concurrently stimulated luteal steroidogenesis and apoptosis, likely by the activation of PKA/CREB/PPARG pathway, providing novel insights into stress-related glucocorticoids on luteal function, and reproductive health in mammals under stress or therapeutic glucocorticoid treatment.