ALLOPREGNANOLONE ALTERS OVARIAN MORPHO-PHISIOLOGY: EFFECTS ON APOPTOSIS AND ANGIOGENESIS.

ASENSIO JOANA; PELLEGRINA LAURA; ANTONELLA R. R. CÁCERES; LACONI MYRIAM

Workshop; International Workshop in Neuroendocrinology; 2015

Introduction: The steroids synthesized and metabolized in the central nervous system are called neurosteroids. They play a central role in the relationship between stress and reproductive biology. Stress is considered one of the main risk factors for reproduction. Allopregnanolone (ALLO) is an active metabolite of progesterone (Pg) involved in physiological and reproductive parameters of female rat. At physiological concentrations, Allo has neuroprotective effects, but under stress conditions has deleterious effects. In previous studies, we found that ALLO inhibited the secretion of luteinizing hormone, as well as the process of ovulation and sexual receptivity. Moreover, Allo was able to inhibit the apoptosis in the corpus luteum. In addition, ALLO increased serum levels of Pg and prolactin (PRL) hormones. Taken together, these findings led us to hypothesize that the effect of ALLO could extend to the ovarian morpho-physiology.Objectives: To determine if a pharmacological dose (via intra-cerebro-ventricular) of ALLO is able to alter morphometric parameters in the rat ovary. We focused in the process of luteal regression, steroid hormones concentration and the process of apoptosis in follicles.Methods and Results: ALLO was injected during proestrus morning and animals were sacrificed 24 and 96 hours post drug administration. Serum PROG and ES levels, cell proliferation and apoptosis in ovarian follicles, and the process of angiogenesis in corpora lutea (CL) were evaluated. Our results indicate that ALLO stimulated apoptosis in ovarian follicles, because ALLO increased the number of atretic follicles and decreased ES levels. Furthermore, ALLO induced decreased expression of proliferation cell nuclear antigen (PCNA) on cells of ovarian follicles, accompanied by a decrease in the number of pre-ovulatory follicles.Conclusions: ALLO exerts a pro-apoptotic effect on developing ovarian follicles and stimulates follicular atresia, with a consequent decrease in production of ES. Furthermore, the number of CL was reduced and the process of apoptosis increased in animals treated with ALLO, and serum Pg increased. These results suggest that ALLO prolongs survival of the CLs, keeping them functional for longer and producing more Pg. ALLO could delay the natural process of luteolysis, through an anti-apoptotic effect on the population of CLs. In an ecological context, these findings can be interpreted as a delay in reproduction process under stressful situations, such as lack of food resources, lack of males or inclement weather such as lack of food resources, lack of males or inclement weather.