Heat stress impairs mice granulosa cell function by diminishing steroids production and inducing apoptosis

Ovarian injury can be induced by heat stress. Mice granulosa cells (GCs) are critical for normal ovarian function and they synthesize a variety of growth factors and steroids for the follicle. Furthermore, the growth, differentiation, and maturate of theca cells and oocyte are dependent upon the synthesis of GCs. Due to the critical biological functions of GCs, we hypothesized that the apoptosis and dysfunction of GCs could also be induced by heat stress. We analyzed GCs apoptosis and evaluated the expression of apoptosis-related genes (caspase-3, Bax, Bcl-2) after heat treatment. Radio immunity assay was used to measure the secretion of 17β-estradiol (E2) and progesterone (P4). RT-PCR was used to evaluate the expression of steroids-related genes (Star, CYP11A1, CYP19A1). Our data suggested that heat stress inhibited GCs proliferation, induced GCs apoptosis, decreased E2 and P4 secretion, reduced the steroids-related genes mRNA expression. Besides, our results indicated that heat treatment-induced apoptosis of GCs through the mitochondrial pathway, which involved caspase-3 and Bax. The reduction in steroids secretion and mRNA expression of Star, CYP11A1, and CYP19A1 might also play a role in heat-induced GCs apoptosis and ovarian injury.