Role of Stress and Stress Hormones on Ovulation and Implantation in Mice: Involvement of Adrenals

Abstract

Studies have revealed that stressful events in women’s life may suppress the reproductive functions viz., pre-fertilization (copulation, oocyte maturation, ovulation), gestational (implantation, placentation, organogenesis) and post–partum (pregnancy rate, live birth delivery, birth weight etc.). However, the exact mechanism underlying is largely unknown. In the female reproductive system, superoxide anion radical and superoxide dismutase (SOD) enzymes play vital role in the ovulation process, oocyte development, progesterone production and implantation. The present study was designed to explore the plausible mechanism of action of psychological stress on ovulation and implantation by targeting SOD activity. Initially a psychological stress model was developed and optimized in mice by full factorial design which showed increased cortisol level along with behavioural changes viz., anhedonia, depression and anxiety. Exposure to psychological stress model resulted in irregular estrous cyclicity with increased number of atretic antral follicle and pyknotic granulosa cell in mice. Also, the total SOD activity and expression of SOD1 and SOD2 was upregulated in stressed mice during estrous cycle stages. Hormone assay showed increased Luteinizing hormone and progesterone level in stressed cycling mice. The mice were also superovulated to understand the effect of stress on oocyte maturation and it was observed that only immature oocytes were obtained in stressed mice. Implantation is yet another important process of reproductive functions which is required for successful pregnancy and affected by maternal psychological stress. It was observed that exposure to psychological stress inhibits the implantation in pregnant stressed mice. In addition, the activity and expression of SOD1 and SOD2 was upregulated during implantation window in stressed mice. Significant reduction in progesterone and increased estradiol level was also observed in stressed pregnant mice. Later, the mice were adrenalectomized (ADX) to determine the involvement of adrenals on stress response. No reduction in implantation sites was observed in stressed ADX mice group. Similarly, SOD activity in stressed ADX mice is comparable to normal mice. Thus, it showed that absence of adrenals may resulted reduced cortisol level and decreased sensitivity to stress. Based on these findings, it was inferred that psychological stress induced reproductive dysfunctions are linked with increased SOD activity which dysregulate the oxidant and antioxidant balance required for ovulation and implantation.