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

Federica Ghersa, F Ghersa, María Belén Delsouc, M B Delsouc, Alicia A. Goyeneche, A A Goyeneche, S S Vallcaneras, Sandra Vallcaneras, Gabriela Meresman, G Meresman, C M Telleria, Carlos M Telleria, Marilina Casais, M Casais
Molecular human reproduction · 2019 · vol. 25(7) , pp. 385–396 · doi:10.1093/molehr/gaz026 · PMID:31070761 · W2944122521
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TNFRp55 deficient mice exhibited reduced peritoneal TNFα and increased lesion reinnervation markers, suggesting an anti-inflammatory state promotes lesion reinnervation.

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Abstract

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. 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 4 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 expressions 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 reinnervation of endometriotic-like lesions in TNFRp55-/- mice. Chronic deregulation of TNF receptors can have serious consequences for women with advanced endometriosis.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometrium Endometrium Inflammation Inflammation Receptors, Tumor Necrosis Factor, Type I Receptors, Tumor Necrosis Factor, Type I Tumor Necrosis Factor Decoy Receptors Tumor Necrosis Factor Decoy Receptors Animals Apoptosis Apoptosis Apoptosis Blotting, Western Cyclooxygenase 2 Cyclooxygenase 2 Cyclooxygenase 2 Endometriosis Endometrium

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