Reduced inflammatory state promotes reinnervation of endometriotic-like lesions in TNFRp55 deficient mice

GHERSA, FEDERICA; DELSOUC, MARÍA B.; GOYENECHE, ALICIA A.; VALLCANERAS, SANDRA; MERESMAN, GABRIELA; TELLERIA, CARLOS M.; CASAIS, MARILINA

MOLECULAR HUMAN REPRODUCTION.

OXFORD UNIV PRESS

Año: 2019

1360-9947

Endometriosis is a chronic gynecological disease, characterized by growth of endometrial tissue in ectopic sites due to alteration of peritoneal homeostasis and deregulation of apoptosis. Here we have examined whether TNFRp55 deficiency modulates the pro-inflammatory state and the reinnervation of endometriotic-like lesions in mice. Two-month-old female C57BL/6 mice, eight wild type (WT) and eight TNFRp55-/- (KO), were used in the study. The endometriotic-like lesions were induced experimentally. The right uterine horn was removed from the animal, divided longitudinally, cut in three square pieces, and sutured to the intestine mesentery. After four weeks, the lesions and the peritoneal fluid were collected. The level of TNFα in the peritoneal fluid was evaluated by enzyme-linked immunosorbent assay (EIA). The expression of COX2, GRα, and GRβ were evaluated in the lesions by western blot and immunohistochemistry. β-III TUBULIN, BDNF, and NGF protein concentrations were evaluated in the lesions by western blot. Gene expression of Pgp 9.5, SP and Th, was analyzed by RT-PCR, whereas relative concentrations of TRKA, NTRp75, phosphorylated NFκB (pNFκB) and total NFκB in lesions were measured by EIA. Compared with the WT group, the KO mice showed lower TNFα levels in the peritoneal fluid and lower numbers of COX2 immunoreactive cells along with increased expression of GRα, β-III TUBULIN, Pgp 9.5, SP, Th, BDNF, NGF, NTRp75, and pNFκB in the lesions. Future histological studies will be necessary to confirm the sensory/sympathetic imbalance in the endometriotic-like lesions of the KO mice. Our results suggest that a reduced inflammatory state promotes the reinnervation of endometriotic-like lesions in TNFRp55-/- mice. Chronic deregulation of TNF receptors can have serious consequences for women with advanced endometriosis.