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

肥胖调节炎症和脂质代谢卵母细胞基因表达:单细胞转录组视角

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

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.

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.

Trial registration

ClinicalTrials.gov NCT01480024.

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