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

ASENSIO JA; PELEGRINA LT; CÁCERES ARR; PARBORELL F; LACONI MR

Mendoza

Congreso; Workshop Internacional de Neuroendocrinología (IWNE); 2015

ALLOPREGNANOLONE ALTERS OVARIAN MORPHO-PHISIOLOGY: EFFECTS ON APOPTOSIS AND ANGIOGENESIS.ASENSIO Joana1, PELLEGRINA Laura1, CASERES Antonella1, PARBORELL Fernanda2, LACONI Myriam1.1Instituto de Investigaciones Biomédicas (INBIOMED), Universidad de Mendoza, IMBECU-CONICET, Mendoza, Argentina.2Instituto de Biología y Medicina Experimental, IBYME- CONICET, Buenos Aires, Argentina.Introduction: The steroids synthesized and metabolized in the central nervous system are called neurosteroids and play a central role in the relationship between stress and reproduction. Stress is considered a risk factor for reproductive process. Allopregnanolone (ALLO) is an active metabolite of progesterone (Pg) involved in physiological and reproductive parameters of female rat. In 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 inhibited apoptosis in corpus luteum (CL), increased serum levels of Pg and prolactin hormones. Taken together, these findings led us to hypothesize that the effect of ALLO could extend to the ovarian morpho-physiology.Objectives: To determine whether 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 administration. Serum PROG and ES levels, cell proliferation and apoptosis in ovarian follicles, and the process of angiogenesis in 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, in animals treated with ALLO the number of CL was reduced, the process of apoptosis increased and serum Pg increased. These results suggest that ALLO prolongs survival of CL, 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, males or inclement weather.Financial support: Grant 133/10 Universidad de Mendoza, PIP 11220100100126 CONICET, Grant from Universidad MAZA for Dr M. Laconi and official support of Provincial Health Ministry.