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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #341534
Title: Obesity modulates inflammation and lipid metabolism oocyte gene expression: A single cell transcriptome perspective

Author
item RUEBEL, MEGHAN - Michigan State University
item COTTER, MATTHEW - Arkansas Children'S Nutrition Research Center (ACNC)
item SIMS, CLARK - Arkansas Children'S Nutrition Research Center (ACNC)
item MOUTOS, DEAM - Arkansas Fertility & Gynecology
item Badger, Thomas - Arkansas Children'S Nutrition Research Center (ACNC)
item CLEVES, MARIO - Arkansas Children'S Nutrition Research Center (ACNC)
item KARTIK, SHANKAR - Arkansas Children'S Nutrition Research Center (ACNC)
item ANDRES, ALINE - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Journal of Clinical Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/10/2017
Publication Date: 3/15/2017
Citation: Ruebel, M.L., Cotter, M., Sims, C.R., Moutos, D.M., Badger, T.M., Cleves, M.A., Kartik, S., Andres, A. 2017. Obesity modulates inflammation and lipid metabolism oocyte gene expression: A single cell transcriptome perspective. Journal of Clinical Endocrinology and Metabolism. doi:10.1210/jc.2016-3524.

Interpretive Summary: Obesity in women has been shown to lead to a higher prevalence of infertility and pregnancy complications. Research has also shown that obesity in pregnant mothers leads to an increased risk of obesity in their offspring. The reasons for these outcomes are not fully understood, but it is possible that maternal obesity-associated factors influence developmental programming of a child even prior to conception. To address these questions, the effect of obesity on different hormones and metabolites was studied in the serum and follicular fluid (the fluid surrounding the oocyte) of women undergoing fertility treatments. Gene expression of single cell oocytes was also characterized. Higher adiposity (the amount of body fat) was marked by elevated concentrations of obesity-associated hormones and metabolites in the blood and follicular fluid. Furthermore, oocyte genes that are involved in inflammation, fat metabolism, and stress were changed. These results indicate that an increase in adiposity of mothers, due to obesity, leads to significant alterations in the ovarian environment and oocytes prior to conception. This raises the possibility that obesity-related changes in the oocyte milieu is involved in early mechanisms that modify development in children born to obese mothers.

Technical Abstract: This study aimed to compare oocyte gene expression profiles and follicular fluid (FF) content from overweight/obese (OW) women and normal weight (NW) women who were undergoing fertility treatments. Using single cell transcriptomic analyses, we investigated oocyte gene expression using RNA-seq. Serum and FF contents were quantified using ELISA and colorimetric assays. Eleven OW women and 13 NW women undergoing fertility treatments were enrolled. Oocyte mRNA profiles as well as serum and FF hormone and lipid levels were assessed. OW women had significantly higher BMI, body fat percentage, and serum HOMA-IR compared to NW women (p<0.01). Serum leptin and C-reactive protein (CRP) levels as well as FF leptin, CRP and triglycerides levels were increased (p<0.05) in OW compared to NW women. Oocytes from OW women had increased expression of pro-inflammatory (CXCL2, p=0.071) and oxidative stress-related (DUSP1, p=0.051) genes; whereas, expression of GAS7 (fat metabolism, p=0.065), TXNIP (oxidative stress, p=0.055) and transcription factors ID3 (p=0.075) and TWIST1(p=0.09) were decreased compared to NW women. These findings provide evidence for significant influence of body composition on oocyte transcript abundance of women undergoing hormonal induction to retrieve oocytes. It further identifies the potential for maternal diet (specifically saturated fat intake) to influence oocyte gene expression. The pre-conception period is, therefore, an important window of opportunity to consider for lifestyle interventions. We studied oocyte mRNA profiles as well as serum and follicular fluid hormone and lipid levels in obese compared to normal weight women and found significant differences.