Research article
22 Jun 2017
Research article | 22 Jun 2017
Spontaneous endometriosis in rhesus macaques: evidence for a genetic association with specific Mamu-A1 alleles
Ivanela Kondova1, Gerco Braskamp1,†, Peter J. Heidt1, Wim Collignon1, Tom Haaksma1, Nanine de Groot2, Nel Otting2, Gaby Doxiadis2, Susan V. Westmoreland3, Eric J. Vallender4,5, and Ronald E. Bontrop2
Ivanela Kondova et al.
Ivanela Kondova1, Gerco Braskamp1,†, Peter J. Heidt1, Wim Collignon1, Tom Haaksma1, Nanine de Groot2, Nel Otting2, Gaby Doxiadis2, Susan V. Westmoreland3, Eric J. Vallender4,5, and Ronald E. Bontrop2
- 1Animal Science Department, Division of Pathology and
Microbiology, Division of Veterinary care, Biomedical Primate Research
Centre, 2288 GJ Rijswijk, the Netherlands
- 2Department of Comparative Genetics, Biomedical Primate Research
Centre, 2288 GJ Rijswijk, the Netherlands
- 3AbbVie Bioresearch Center, Immunology, Pharmacology, Pathology and
Exploratory Toxicology, Worcester, MA 01605, USA
- 4Department of Psychiatry and Human Behavior, University of Mississippi
Medical Center, Jackson, MS 39216, USA
- 5Division of Veterinary Medicine, Tulane National Primate Research
Center, Covington, LA 70433, USA
- †deceased
- 1Animal Science Department, Division of Pathology and
Microbiology, Division of Veterinary care, Biomedical Primate Research
Centre, 2288 GJ Rijswijk, the Netherlands
- 2Department of Comparative Genetics, Biomedical Primate Research
Centre, 2288 GJ Rijswijk, the Netherlands
- 3AbbVie Bioresearch Center, Immunology, Pharmacology, Pathology and
Exploratory Toxicology, Worcester, MA 01605, USA
- 4Department of Psychiatry and Human Behavior, University of Mississippi
Medical Center, Jackson, MS 39216, USA
- 5Division of Veterinary Medicine, Tulane National Primate Research
Center, Covington, LA 70433, USA
- †deceased
Correspondence: Ivanela Kondova (kondova@bprc.nl)
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Received: 20 Dec 2016 – Revised: 19 Apr 2017 – Accepted: 28 Apr 2017 – Published: 22 Jun 2017
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 (p = 0.007), and Mamu-A1*007, 21.9 % NEPRC rhesus macaques vs. 6.7 %, (p = 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.
