Important role of collective cell migration and nerve fiber density in the development of deep nodular endometriosis

Abstract

Objective: To evaluate deep nodular endometriotic lesions induced in baboons over 12 months and analyze collective cell migration and nerve fiber density.

Design: Morphologic and immunohistochemical analysis of endometriotic lesions induced in baboons over the course of 1 year.

Setting: Academic research unit.

Animal(s): Three female baboons (Papio anubis).

Intervention(s): Recovery of induced deep nodular endometriotic nodules from baboons.

Main outcome measure(s): Evaluation of the morphology of glands by analysis of the center of lesions and the invasion front; immunohistochemical staining with Ki67, E-cadherin, and β-catenin for investigation of mitotic activity and cell-cell junctions, and with protein gene product 9.5 and nerve growth factor (NGF) for study of nerve fiber density (NFD).

Result(s): All (100%) of the lesions were invasive 1 year after induction, compared with 42.29% after 6 months. Glands from the invasion front showed significantly reduced thickness but significantly higher mitotic activity. E-Cadherin and β-catenin expression were similar between the center and front. NFD was significantly higher in lesions induced after 1 year than after 6 months, and NGF expression was significantly lower in 1-year lesions than in 6-month lesions.

Conclusion(s): Nodular endometriotic lesions induced in the baboon model were found to be significantly more invasive and innervated after 12 months than after 6 months. The invasive phenotype was highly expressed in glands at the invasion front, and our study suggests that nerve fibers play a role in the development of lesions as observed in women.

Keywords: Deep nodular endometriosis; baboon model; collective cell migration; invasion; nerve fiber density; nerve fibers.