Morphological and immunohistochemical characterization of spontaneous endometriosis in rhesus macaques (Macaca mulatta).

Eva Gruber-Dujardin,Kerstin Mätz-Rensing,Martina Bleyer

doi:10.5194/pb-4-77-2017

Eva Gruber-Dujardin, Kerstin Mätz-Rensing + Show 1 more

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https://doi.org/10.5194/pb-4-77-2017

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Journal: Primate biology	Publication Date: Apr 13, 2017
Citations: 5	License type: CC BY 3.0

Affiliation: German Primate Center

Abstract

Several cases of spontaneous endometriosis in middle-aged to old rhesus macaques (Macaca mulatta) from the breeding colony of the German Primate Center were thoroughly characterized with regards to anatomical distribution and macroscopic appearance, histological differentiation and immunohistochemical profile including somatic markers, hormonal receptors, and proliferation indices. More than half of the examined animals (five of nine) were directly related to one breeding male, supporting a strong genetic predisposition. Histologically, four different types of endometriotic lesions, depending on the degree of ectopic endometrial gland and stromal differentiation (well differentiated, purely stromal, mixed differentiation, poorly differentiated), could be constantly identified within all animals. Immunohistochemistry (IHC) of cytokeratin (CK), vimentin, smooth muscle actin (SMA), desmin, estrogen (ER), and progesterone (PR) receptors as well as of the nuclear proteins Ki67 and p53 revealed varying staining patterns in the four different types of endometriosis differentiation and compared to normal endometrium. Purely stromal, mixed, or poorly differentiated lesions, especially, showed additional cytokeratin-positive stromal cells, whereas epithelial cells of endometriosis with mixed or poor differentiation increasingly expressed mesenchymal markers (vimentin, SMA). Hormonal receptor and Ki67 expression in well-differentiated endometriotic lesions mostly reflected that of normal endometrial tissue according to the cyclic phase of the animal, while the expression gradually diminished with decreasing grade of differentiation. However, increased nuclear accumulations of p53 antigen could only be continuously detected in epithelial cells of mixed or poorly differentiated endometriosis. Altogether, these findings support the pathogenetic theory of coelomic metaplasia, since the expression profiles of somatic markers in less differentiated forms closely resembled that of mesothelial cells. Thus, the four different histological types of endometriosis might display subsequent grades of differentiation in the course of time, with poorly differentiated types representing newly formed, immature lesions and well-differentiated types being older, fully differentiated forms, rather than being the outcome of dedifferentiation processes.

Highlights

Endometriosis is a common chronic gynaecological disorder in women, with a prevalence of at least 10 % (Giudice and Kao, 2004; Brosens et al, 2016), which occurs in several Old World primate species that have a menstrual cycle (Assaf and Miller, 2012; Barrier et al, 2007; Dick et al, 2003; Wilkinson et al, 2008; Zondervan et al, 2004)
Additional macroscopic findings related to endometriosis and representing the cause of death in three animals were severe hemoperitoneum or suppurative peritonitis with multiple abscesses and septicemia, accompanied by rectal perforation in case 8
The results of this study provide a comprehensive overview of the clinical, macroscopic, and microscopic manifestations of spontaneous endometriosis in rhesus macaques (Macaca mulatta), emphasizing important aspects of diagnostic relevance and possible pathogenetic implications

Summary

Introduction

Endometriosis is a common chronic gynaecological disorder in women, with a prevalence of at least 10 % (Giudice and Kao, 2004; Brosens et al, 2016), which occurs in several Old World primate species that have a menstrual cycle (Assaf and Miller, 2012; Barrier et al, 2007; Dick et al, 2003; Wilkinson et al, 2008; Zondervan et al, 2004). The pathogenetic mechanism most widely accepted as a prerequisite for the development of endometriotic lesions is retrograde menstruation that is the distribution and implantation of refluxed endometrial material within the peritoneal cavity (Sampson, 1927; for review: Brosens and Brosens, 2000b) This theory is supported by the frequent involvement of pelvic organs and the fact that this disease almost exclusively develops in women or female nonhuman primates that are menstruating. Increasing numbers of publications point to an important role of stem or progenitor cells, respectively, in the pathogenesis of endometriosis (Forte et al, 2014; Forte et al, 2009; Gotte et al, 2011; Matthai et al, 2006; Sasson and Taylor, 2008)

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