Avaliação do eixo ECA2/angiotensina (1-7)/receptor mas em células da granulosa-luteinizadas de mulheres inférteis e no processo de indução da ovulação para fertilização in vitro

Abstract

Objective: To evaluate the RAS (renin-angiotensin system) behaviour during ovulation induction for IVF. To determine the expression of Mas receptor (rMas), ACE (angiotensin converting enzime) and ACE2 in human granulosa-lutein (GL) cells and its correlation with angiotensin 1-7 [ang-(1-7)] and angiotensin II (ang II) levels. To correlate RAS components with IFV parameters in the total group and between normal responder and low responders. Patients and Methods: This prospective, observational study performed from june to december 2012, in the Professor Aroldo Fernando Camargos Human Reproduction Laboratory from Hospital das Clínicas/UFMG included 64 patients, whose plasma before and after controlled ovarian hyperstimulation for IVF and follicular fluid (FF) were collected for radioimunoassay (RIA) for Ang-(1-7) and Ang-II and for estradiol and progesterone assay. Reverse-transcription polymerase chain reaction analysis for rMas and ECA2 in GL cells was performed. Results: There was a significant increase in Ang-(1-7) and Ang II levels in plasma, after ovulation induction, (p<0,0001). There was no diference between plasma and FF in Ang-(1-7) levels, however the Ang II FF level was threefold higher than plasma level (<0,0001). Ang-(1-7) showed a positive correlation between Ang II, in plasma after ovulation induction (p<0,0001) and in FF (p=0,001). There was no correlation between plasma and FF angiotensins levels. Messenger RNA expression for MAS, ACE and ACE2 was detected in GL cells. There was a positive correlation between MII oocytes and rMas expression, but only in women with more than three MII oocyte collected. A strong correlation between ECA and ECA2 (p<0,0001) and between rMas and ECA2 (p=0,006) was noted. The low responder women had lower ang(1-7) plasma level, after ovulation, and showed a negative correlation between MII oocytes and ang-(1-7) plasma levels and MII oocytes and rMas expression (p=0,0001). The normal responder group showed a positive correlation between MII oocytes and ECA2 expression (p=0,036). There is no correlation between estradiol and progesterone levels with Ang-(1-7), rMas, Eca and ECA2. Conclusions: The sistemic and ovarian RAS is activated during ovulation induction for IVF. Ang-(1-7) and Ang II levels seem to have similar effects in human foliculogenesis. rMas, ACE 2 and ACE mRNA expression in GL cells sugest a paracrine effect of SRA peptides in human ovary after gonadotropin stimulation.