Journal Article

Obesity Modulates Inflammation and Lipid Metabolism Oocyte Gene Expression: A Single-Cell Transcriptome Perspective

Badger, Thomas M., Cotter, Matthew, Shankar, Kartik, Andres, Aline, Cleves, Mario A., Ruebel, Meghan L., Sims, Clark R., Moutos, Dean M.

2017

Overview

Context:It is hypothesized that obesity adversely affects the ovarian environment, which can disrupt oocyte maturation and embryonic development.Objective: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.Design:Using single-cell transcriptomic analyses, we investigated oocyte gene expression using RNA sequencing.Patients or Other Participants:Eleven OW women and 13 NW women undergoing fertility treatments were enrolled.Main Outcome Measures:Oocyte messenger RNA profiles as well as serum and FF hormone and lipid levels were assessed.Results:OW women had significantly higher body mass index, body fat percentage, and serum homeostatic model assessment−insulin resistance index compared with NW women (P < 0.01). Serum leptin and C-reactive protein (CRP) levels as well as FF leptin, CRP, and triglyceride levels were increased (P < 0.05) in OW compared with NW women. Oocytes from OW women had increased expression of proinflammatory (CXCL2; P = 0.071) and oxidative stress–related (DUSP1; P = 0.051) genes but had decreased expression of GAS7 (fat metabolism; P = 0.065), TXNIP (oxidative stress; P = 0.055), and transcription factors ID3 (P = 0.075) and TWIST1 (P = 0.099) compared with NW women.Conclusions:These findings provide evidence for the significant influence of body composition on oocyte transcript abundance in women undergoing hormonal induction to retrieve oocytes. They further identify the potential for maternal diet to influence oocyte gene expression. The preconception 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 women compared with those in normal-weight women and found significant differences.

• Publisher: Endocrine Society,Copyright Oxford University Press,Oxford University Press
• Subject: Adolescent / Adult / Body Composition / Body fat / Body mass index / Body weight / C-reactive protein / C-Reactive Protein - metabolism / Carrier Proteins - genetics / Carrier Proteins - metabolism / Case-Control Studies / Chemokine CXCL2 - genetics / Chemokine CXCL2 - metabolism / Clinical s / Dual Specificity Phosphatase 1 - genetics / Dual Specificity Phosphatase 1 - metabolism / Embryogenesis / Fat metabolism / Female / Fertility / Follicular fluid / Follicular Fluid - chemistry / Gene expression / Gene Expression Profiling / Humans / Inflammation / Inhibitor of Differentiation Proteins - genetics / Inhibitor of Differentiation Proteins - metabolism / Insulin / Insulin resistance / Leptin / Leptin - metabolism / Lipid Metabolism / Lipids / Metabolism / mRNA / Neoplasm Proteins - genetics / Neoplasm Proteins - metabolism / Nerve Tissue Proteins - genetics / Nerve Tissue Proteins - metabolism / Obesity / Obesity - genetics / Obesity - metabolism / Oocyte Retrieval / Oocytes / Oocytes - metabolism / Overweight / Overweight - genetics / Overweight - metabolism / Ovulation Induction / Oxidative metabolism / Oxidative stress / Sequence Analysis, RNA / Single-Cell Analysis / Transcription factors / Transcriptomes / Transcriptomics / Triglycerides - metabolism / Young Adult