Angiotensin (Ang)-(1-7) is an active peptide formed from Ang I or Ang-(1-9) by multiple proteolytic steps involving angiotensin-converting enzyme (ACE) 1 and other peptidases, or by a single cleavage of Ang II catalyzed chiefly by ACE2. The effects of Ang-(1-7) are mediated by the G protein-coupled receptor Mas (or Mas1), encoded by the protooncogene MAS . The reproductive system expresses ACE2 quite abundantly and therefore is able to generate Ang-(1-7) using precursor peptides produced locally or taken from circulation. In several mammalian species, Ang-(1-7) stimulates ovarian follicle growth, oocyte maturation and ovulation. The peptide is found in human endometrium, mostly during the secretory phase of menstrual cycle when the uterus is receptive to embryo implantation. Rat models and human observational studies suggest that Ang-(1-7) is part of the maternal adaptive response to pregnancy and its deficiency is associated with poor circulation in the placental bed. Knockout mice revealed a relevant participation of Mas-mediated stimulus to the maintenance of normal spermatogenesis, even though the animal can still reproduce without it. In addition, the vasorelaxant effect of Ang-(1-7) participates in the physiological mechanism of corpus cavernosum blood influx and penile erection. We conclude that preclinical evidence encourages the pursuit of treatments for female and male reproductive dysfunctions based on Mas agonists, starting with its natural ligand Ang-(1-7).

The polycystic ovary (PCO) syndrome (PCOS) is the most common cause of anovulatory infertility in women and is associated with several clinical disorders. Despite the great amount of research in the area, mechanisms involved in the genesis of this syndrome remain poorly understood. In a recent issue of Clinical Science ( vol. 132, issue 7, 759-776 ), Wang and colleagues, highlight the important role of overactivated C-type natriuretic peptide (CNP) and natriuretic peptide receptor 2 (CNP/NPR2) system in preventing oocyte maturation and ovulation in PCOS mice model induced by androgen. Dehydroepiandrosterone (DHEA) treatment caused anovulation, high levels of androgen and estrogen receptors (AR and ER) in the ovary, high expression of CNP and natriuretic peptide receptor 2 (NPR2) in granulosa cells (GC), and an increase in testosterone and estradiol (E 2 ) levels in sera. The high level of CNP/NPR2 was associated with oocyte meiotic arrest and very low ovulation rate. Treatment with human chorionic gonadotropin (hCG) or inhibitors of AR or ER reduced the level of CNP/NPR2, which resulted in meiotic resumption and ovulation. The article provided important information for understanding the effect of ovarian steroids on control of oocyte maturation and fertility and highlighted CNP/NPR2 as a specific pathway that is potentially involved in the ovulatory disruption in PCOS.

1. Electrolyte transport characteristics were examined in erythrocytes from 13 normal men and from two groups of women: (i) taking combined oral contraceptive preparations (O/C, n = 10), and (ii) ovulatory women (non-O/C, n = 10) pre- and post-ovulation, at the same time intervals (days 7–10 and days 15–18) during a menstrual cycle. 2. With rubidium ( 86 Rb + ) used as a potassium analogue, co-transport (ouabain-resistant, fruse-mide-sensitive 86 Rb + influx) values were found to be lowest in non-O/C women (28 ± se 2.5 nmol h −1 10 −9 cells) and highest in men (56 ± 5.7, P < 0.001), with results between the two in women taking O/C (42 ± 4.2, P < 0.05 vs men, P < 0.01 vs non-O/C). Passive 86 Rb leak (frusemideand ouabain-resistant) was significantly lower in men (13 ± 1.6 nmol h −1 10 −9 cells) than in both groups of women (non-O/C 29 ± 1.8, P < 0.001; O/C 25 ± 1.2, P < 0.001). There was no cyclical variation within either group of women. 3. Maximum ouabain binding (number of Na + ,K + -ATPase units) was the same in all groups. Na + ,K + -ATPase activity, as determined by ouabain-sensitive 86 Rb influx, was the same in men and non-O/C groups, but was significantly suppressed in O/C compared with both men ( P < 0.01) and non-O/C women ( P < 0.05). 4. The differences found were not due to alterations in either progesterone or aldosterone, but could represent an androgenic effect in vivo of the 19-nortestosterone derivatives in combined oral contraceptive preparations.