The influence of prorenin/(pro)renin receptor on progesterone secretion by the bovine corpus luteum

• Published in: Animal reproduction science 2022-06, Vol.241, p.106985-106985, Article 106985
• Main Authors: Dau, Andressa Minussi Pereira, da Rosa, Paulo Roberto, dos Santos, Joabel, Ferst, Juliana, de Macedo, Mariana, Rovani, Monique, Comim, Fabio, Antoniazzi, Alfredo Quites, Gasperin, Bernardo, Ferreira, Rogério, Gonçalves, Paulo Bayard
• Format: Article
• Language: English
• Subjects: Aliskiren; Cattle; Luteolysis; RAS
• ISSN: 0378-4320; 1873-2232
• DOI: 10.1016/j.anireprosci.2022.106985

The aim of this study was to evaluate the role of prorenin/(pro)renin receptor activation on luteal progesterone (P4) secretion. Our hypothesis was that the nonproteolytic activation of (pro)renin receptor [P(RR)] is part of the regulatory mechanism responsible for corpus luteum (CL) function. In the first three experiments, prorenin was found to stimulate the production of P4, which is not inhibited by an angiotensin receptor antagonist (saralasin), but rather by a renin/prorenin inhibitor (aliskiren), a MAPK1/3 inhibitor (PD325901) or an EGFR inhibitor (AG1478), which are evidence of nonproteolytic activation of prorenin. Moreover, prorenin induced phosphorylation of MAPK1/3 in luteal cells. Following these in vitro experiments, a sequence of in vivo experiments was performed demonstrating that the intrafollicular injection of aliskiren in preovulatory follicles impaired P4 secretion in cows that ovulated. Furthermore, all profibrotic genes studied were present in the CL and TGFB1 and FN1 mRNA were upregulated from day 5–10 post-ovulation. During luteolysis, REN was downregulated at 48 h, whereas TGFB1 and SERPINE1 were dramatically upregulated in luteal tissue at 12 h after PGF. In summary, these data are evidence that nonproteolytic activation of (P)RR is involved in luteal function.