Spontaneous endometriosis in rhesus macaques: evidence for a genetic association with specific Mamu-A1 alleles.

Ivanela Kondova,Eric J Vallender,Wim Collignon,Peter J Heidt,Gaby Doxiadis,Tom Haaksma,Gerco Braskamp,Nel Otting,Susan V Westmoreland,Ronald E Bontrop,Nanine De Groot

doi:10.5194/pb-4-117-2017

Ivanela Kondova, Eric J Vallender + Show 9 more

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https://doi.org/10.5194/pb-4-117-2017

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Journal: Primate biology	Publication Date: Jun 22, 2017
Citations: 1	License type: CC BY 3.0

Affiliation: University of Mississippi Medical Center

Abstract

Endometriosis is a poorly understood common debilitating women's reproductive disorder resulting from proliferative and ectopic endometrial tissue associated with variable clinical symptoms including dysmenorrhea (painful menstrual periods), dyspareunia (pain on intercourse), female infertility, and an increased risk of malignant transformation. The rhesus macaque (Macaca mulatta) develops a spontaneous endometriosis that is very similar to that seen in women. We hypothesized that specific major histocompatibility complex (MHC) alleles may contribute to the pathogenesis of endometriosis. As part of a collaboration between the Biomedical Primate Research Centre (BPRC) in the Netherlands and the New England Primate Research Center (NEPRC) in the United States, we analyzed DNA sequences of MHC class I (Macaca mulatta, Mamu-A1) and class II (Mamu-DRB) alleles from rhesus macaques with endometriosis and compared the allele frequencies with those of age-matched healthy macaques. We demonstrate that two MHC class I alleles are overrepresented in diseased macaques compared to controls: Mamu-A1*001, 33.3 % in BPRC animals with endometriosis vs. 11.6 % in healthy macaques ( 0.007), and Mamu-A1*007, 21.9 % NEPRC rhesus macaques vs. 6.7 %, ( 0.003). We provide evidence that select MHC class I alleles are associated with endometriosis in rhesus macaques and suggest that the disease pathogenesis contribution of MHC class I warrants further research.

Highlights

1.1 Endometriosis in humansEndometriosis is a chronic debilitating inflammatory disease that affects approximately 10 to 20 % of women of reproductive age and roughly 50 % of women with infertility (Giudice, 2010)
The aim of our study is to examine any genetic susceptibility of major histocompatibility complex (MHC) alleles to endometriosis in two colonies of rhesus macaques
Eight female rhesus macaques from Biomedical Primate Research Centre (BPRC) and seventeen female rhesus macaques from New England Primate Research Center (NEPRC) (14 to 20 years of age, mean 15.9 years) were identified with endometriosis based on clinical and histologic diagnoses (Figs. 1, 2, and 3)

Summary

Introduction

1.1 Endometriosis in humansEndometriosis is a chronic debilitating inflammatory disease that affects approximately 10 to 20 % of women of reproductive age and roughly 50 % of women with infertility (Giudice, 2010). The associated clinical symptoms like dysmenorrhoea, dyspareunia, and chronic pelvic pain have a negative impact on the quality of life of women affected with the disorder (Gupta et al, 2008). It is likely that endometriosis is a complex and multifactorial disorder triggered by hormonal, immunologic, genetic, and environmental factors. One hypothesized process in the pathogenesis of endometriosis is metaplasia, involving the transformation of tissues in the peritoneal cavity into endometrial tissue driven by hormonal or immunological factors (Sourial et al, 2014). Other hypothesized processes include the suppression of normal apoptosis of endometrial glandular cells, proliferation of a population of progenitor or stem cells, epigenetic alterations (Forte et al, 2014), and the oldest theory of retrograde menstruation (Sampson, 1927)

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