Superior mesenteric ganglion neural modulation of ovarian angiogenesis, apoptosis, and proliferation by the neuroactive steroid allopregnanolone.

CÁCERES, ANTONELLA R. R.; CAMPOVERDE ARBOCCO, FIORELLA; CARDONE, DANIELA A.; SANHUEZA, MARIA DE LOS ANGELES; CASAIS MARILINA; VEGA OROZCO, ADRIANA; LACONI MYRIAM RAQUEL

JOURNAL OF NEUROENDOCRINOLOGY.

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2021

0953-8194

Allopregnanolone (ALLO), a potent neuroactive steroid, is active and synthesized in the peripheral nervous system. Previous studies have shown that ALLO participates in the central regulation of reproduction with effects on the ovarian physiology, although there is little evidence for its ability to modulate peripheral tissues. The aim of this work was to elucidate if ALLO, administered to an ex vivo system that comprises the superior mesenteric ganglion (SMG), the ovarian nervous plexus (ONP) and the ovary (O), or to the denervated ovary (DO), was able to modify ovarian apoptosis, proliferation, and angiogenesis. For this purpose, the SMG-ONP-O system and the DO were incubated during 120 minutes at 37 ºC, in the presence of two ALLO doses (0.06µM and 6µM). The intrinsic and extrinsic pathways of apoptosis were analyzed. After the incubation of the SMG-ONP-O system with ALLO 0.06µM, the BAX/Bcl-2 ratio increased, and the in Fas-L mRNA levels decreased. ALLO 6µM induced a decrease of Fas-L levels. The DO incubation with ALLO 0.06µM induced FAS-L decrease, ALLO 6µM significantly increased it. Cyclin D1 mRNA was measured to evaluate proliferation. The treatment with ALLO 6µM increased proliferation in both the SMG-ONP-O and DO systems. ALLO 0.06µM produced an increase of Cyclin D1 on the DO incubation only. The ovarian expression of VEGF was increased after the SMG-ONP-O system incubation, and decreased in the DO system, after administration of both ALLO doses. ALLO 6µM induced ovarian sensitization to GABA by increasing GABAA receptor expression. In conclusion, ALLO participates in the peripheral neural modulation of ovarian physiology, and can also interact directly with the ovarian tissue, modulating key mechanisms involved in normal and pathological processes in a dose-dependent manner.