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

CÁCERES GIMENEZ, ANTONELLA; CAMPO VERDE ARBOCCÓ, FIORELLA; CARDONE, DANIELA; SANHUEZA, MARIA; CASAIS, MARILINA; VEGA OROZCO, ADRIANA; LACONI, MYRIAM

JOURNAL OF NEUROENDOCRINOLOGY.

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2021

0953-8194

Allopregnanolone (ALLO), a potent neuroactive steroid, is synthesized and active in theperipheral nervous system. Previous studies have shown that ALLO participates in thecentral regulation of reproduction with effects on ovarian physiology, although there islittle evidence for its ability to modulate peripheral tissues. The aim of this work was toelucidate if ALLO, administered to an ex vivo system that comprises the superiormesenteric ganglion (SMG), the ovarian nervous plexus (ONP) and the ovary (O), or tothe denervated ovary (DO), was able to modify ovarian apoptosis, proliferation, andangiogenesis. For this purpose, the SMG-ONP-O system and DO were incubated during120 minutes at 37 ºC, in the presence of two ALLO doses (0.06µM and 6µM). Theintrinsic and extrinsic pathways of apoptosis were analyzed. Incubation of the SMGONP-O system with ALLO 0.06µM led to an increase in the BAX/Bcl-2 ratio and areduction of Fas-L mRNA levels. ALLO 6µM induced a decrease of Fas-L levels.Incubation of DO with ALLO 0.06µM reduced FAS-L, whereas ALLO 6µM significantlyincreased it. Cyclin D1 mRNA was measured to evaluate proliferation. Treatment withALLO 6µM increased proliferation in both SMG-ONP-O and DO. ALLO 0.06µMproduced an increase of Cyclin D1 in DO only. Administration of either ALLO dose led toa higher ovarian expression of VEGF in the SMG-ONP-O system, but a lower one in theDO system. ALLO 6 µM induced ovarian sensitization to GABA by increasing GABAAreceptor expression. In conclusion, ALLO participates in the peripheral neuralmodulation of ovarian physiology. It can also interact directly with the ovarian tissue,modulating key mechanisms involved in normal and pathological processes in a dosedependent manner.