Rhesus Macaque Omental Adipose Tissue

Endometriosis occurs in nonhuman primates at similar rates to humans and is associated with signs of discomfort particularly during menstruation. It has been noted that humans with polycystic ovary syndrome (PCOS) are at elevated risk for development of endometriosis. PCOS is associated with both hyperandrogenemia and obesity, which have also been linked as potential exacerbators of endometriosis; therefore, the current study sought to determine how these factors may impact the progression of spontaneous endometriosis both separately and combined. Female rhesus macaques began treatment on testosterone (T; serum levels approximately 1.35 ng/mL), western style diet (WSD; 36% of calories from fat compared to 16% in standard monkey chow) or the combination (T+WSD) at the time of menarche. Diagnosis of endometriosis by veterinarian staff was achieved by ultrasound or laparoscopy. Severity of endometriosis was determined based on ASRM revised criteria, and staged I-IV. Stages I and II were associated with extent of abdominal adhesions, while Stages III and IV were associated with presence of chocolate cysts. Time to diagnosis from first abdominal surgical procedure was analyzed by laparoscopic and ultrasound procedures. The combined treatment of T+WSD resulted in earlier onset of endometriosis, and more severe types associated with chocolate cysts compared to all other treatments, despite all females undergoing a similar number of laparoscopic procedures. There was a strong correlation between glucose clearance, HOMA-IR and total percentage of body fat with presence of cysts, indicating possible indirect contribution of hyperandrogenemia via metabolic dysfunction. A RNA-seq analysis of omental adipose tissue revealed 474 differentially expressed gene products, with significant impacts in gene members of inflammatory signaling pathways. The interactions between obesity, hyperandrogenemia and endometrial hyperplasia deserves increased investigation in primate species.