Sensorial innervation of endometriotic lesions is favored in a mouse TNFRp55 deficient model

VALLCANERAS S; CASAIS M; DELSOUC MB; GHERSA F; MERESMAN G

Concón

Workshop; 4th International Workshop in Neuroendocrinology; 2017

Endometriosis (EDT) is a chronic inflammatory and oestrogen dependent disease that affects 10-15% of women in their reproductive years causing pain and subfertility. This pathology implicates multiple factors, among these; cytokines play a crucial role, being TNFα the most representative of them. This protein is raised in women with EDT and acts via two distinct membrane receptors, TNFRp55 and TNFRp75, whose expression is altered in this disease. Using a C57BL/6 TNFRp55 -/- knockout mouse model (KO) with surgically induced EDT we have recently reported that there is an increase in lesion size and weight supported by augmented cell proliferation and diminished apoptosis rate compared to C57BL/6 wild-type mice (WT). Interestingly, estradiol levels in peritoneal fluid (PF) of KO mice were increased, suggesting that TNFRp55 deficiency collaborates with oestrogen synthesis.In base of these results and knowing that estradiol can modulate the sensorial innervation in EDT; using the same experimental model, we proposed to study the neurotrophic capacity of the endometriotic-like lesions focusing in neural growth factor (NGF) and its receptors, TrkA and NTRp75. We induced EDT surgically in WT and KO mice by implantation of uterine horn segments on intestinal mesentery. After 30 days, lesions and PF were collected. Gene expression of general (PGP9.5) and sensorial(CGRP and SP) innervation markers, as well as NGF and its receptors, were analyzed by RT-PCR. NGF protein concentration was assessed by Western Blot and ELISA. Relative concentrations of NGF receptors were measured by ELISA and immunofluorescence (IF) of NTRp75 was performed. Our results demonstrated that in comparison to WT group, KO mice exhibited: higher PGP9.5, CGRP y SP mRNA expression (p