Adipocyte alterations in endometriosis: reduced numbers of stem cells and microRNA induced alterations in adipocyte metabolic gene expression

• Published in: Reproductive biology and endocrinology Vol. 17; no. 1; pp. 36 - 10
• Main Authors: Zolbin, Masoumeh Majidi, Mamillapalli, Ramanaiah, Nematian, Sepide E, Goetz, Teddy G, Taylor, Hugh S
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 15.04.2019; BioMed Central; BMC
• Subjects: Adipocytes; Adipocytes - metabolism; Adipocytes - pathology; Adiponectin; Adipose tissue; Animals; Antibiotics; Body fat; Body mass index; Cancer; Cell Differentiation - genetics; Cell number; Cell Proliferation; Chromosome 3; Diabetes; Endometriosis; Endometriosis - genetics; Endometriosis - metabolism; Endometriosis - pathology; Estrogens; Fat metabolism; Fat tissue; Female; Flow cytometry; Gene Expression; Genes; Genetic research; House mouse; Humans; Infertility; Inflammatory diseases; Insulin; Insulin resistance; Insulin Resistance - genetics; Interleukin 6; Leptin; Let-7; Lipid Metabolism; Medical research; Mesenchyme; Metabolism; Mice, Inbred C57BL; MicroRNA; MicroRNAs; MicroRNAs - metabolism; MiR; miRNA; Obesity; Peroxisome proliferator-activated receptors; Phenols (Class of compounds); Physiological aspects; Proliferating cell nuclear antigen; Proliferating Cell Nuclear Antigen - metabolism; RNA; Statistics; Stem cell transplantation; Stem cells; Womens health; United States > US; microRNAs; miR-342; MiR; Stem cells; Endometriosis; Adipocytes; Let-7; Fat tissue
• ISSN: 1477-7827; 1477-7827
• DOI: 10.1186/s12958-019-0480-0

Endometriosis is an estrogen dependent, inflammatory disorder occurring in 5-10% of reproductive-aged women. Women with endometriosis have a lower body mass index (BMI) and decreased body fat compared to those without the disease, yet few studies have focused on the metabolic abnormalities in adipose tissue in women with endometriosis. Previously, we identified microRNAs that are differentially expressed in endometriosis and altered in the serum of women with the disease. Here we explore the effect of endometriosis on fat tissue and identified a role for endometriosis-related microRNAs in fat metabolism and a reduction in adipocyte stem cell number. Primary adipocyte cells cultured from 20 patients with and without endometriosis were transfected with mimics and inhibitors of microRNAs 342-3p or Let 7b-5p to model the status of these microRNAs in endometriosis. RNA was extracted for gene expression analysis by qRT-PCR. PCNA expression was used as a marker of adipocyte proliferation. Endometriosis was induced experimentally in 9-week old female C57BL/6 mice and after 10 months fat tissue was harvested from both the subcutaneous (inguinal) and visceral (mesenteric) tissue. Adipose-derived mesenchymal stem cells in fat tissue were characterized in both endometriosis and non-endometriosis mice by FACS analysis. Gene expression analysis showed that endometriosis altered the expression of Cebpa, Cebpb, Ppar-γ, leptin, adiponectin, IL-6, and HSL, which are involved in driving brown adipocyte differentiation, appetite, insulin sensitivity and fat metabolism. Each gene was regulated by an alteration in microRNA expression known to occur in endometriosis. Analysis of the stem cell content of adipose tissue in a mouse model of endometriosis demonstrated a reduced number of adipocyte stem cells. We demonstrate that microRNAs Let-7b and miR-342-3p affected metabolic gene expression significantly in adipocytes of women with endometriosis. Similarly, there is a reduction in the adipose stem cell population in a mouse model of endometriosis. Taken together these data suggest that endometriosis alters BMI in part through an effect on adipocytes and fat metabolism.