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

ABSTRACT: It is hypothesized that obesity adversely affects the ovarian environment, which can disrupt oocyte maturation and embryonic development.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 sequencing.Eleven OW women and 13 NW women undergoing fertility treatments were enrolled.Oocyte messenger RNA profiles as well as serum and FF hormone and lipid levels were assessed.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.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.

SUBMITTER: Ruebel ML

PROVIDER: S-EPMC5470765 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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

Ruebel Meghan L ML Cotter Matthew M Sims Clark R CR Moutos Dean M DM Badger Thomas M TM Cleves Mario A MA Shankar Kartik K Andres Aline A

The Journal of clinical endocrinology and metabolism 20170601 6

<h4>Context</h4>It is hypothesized that obesity adversely affects the ovarian environment, which can disrupt oocyte maturation and embryonic development.<h4>Objective</h4>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.<h4>Design</h4>Using single-cell transcriptomic analyses, we investigated oocyte gene expression using RNA sequencing.<h4>Patients o ...[more]

PMID: 28323970

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Project description:BackgroundMammalian follicle development is characterized by extensive changes in morphology, endocrine responsiveness, and function, providing the optimum environment for oocyte growth, development, and resumption of meiosis. In cattle, the first signs of transcription activation in the oocyte are observed in the secondary follicle, later than during mouse and human oogenesis. While many studies have generated extensive datasets characterizing gene expression in bovine oocytes, they are mostly limited to the analysis of fully grown and matured oocytes. The aim of the present study was to apply single-cell RNA sequencing to interrogate the transcriptome of the growing bovine oocyte from the secondary follicle stage through to the mid-antral follicle stage.ResultsSingle-cell RNA-seq libraries were generated from oocytes of known diameters (< 60 to > 120 μm), and datasets were binned into non-overlapping size groups for downstream analysis. Combining the results of weighted gene co-expression network and Trendy analyses, and differently expressed genes (DEGs) between size groups, we identified a decrease in oxidative phosphorylation and an increase in maternal -genes and transcription regulators across the bovine oocyte growth phase. In addition, around 5,000 genes did not change in expression, revealing a cohort of stable genes. An interesting switch in gene expression profile was noted in oocytes greater than 100 μm in diameter, when the expression of genes related to cytoplasmic activities was replaced by genes related to nuclear activities (e.g., chromosome segregation). The highest number of DEGs were detected in the comparison of oocytes 100-109 versus 110-119 μm in diameter, revealing a profound change in the molecular profile of oocytes at the end of their growth phase.ConclusionsThe current study provides a unique dataset of the key genes and pathways characteristic of each stage of oocyte development, contributing an important resource for a greater understanding of bovine oogenesis.

Dataset Information

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

Publications

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

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