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Short-term Western-style diet negatively impacts reproductive outcomes in primates
Sweta Ravisankar, … , Shawn L. Chavez, Jon D. Hennebold
Sweta Ravisankar, … , Shawn L. Chavez, Jon D. Hennebold
Published February 22, 2021
Citation Information: JCI Insight. 2021;6(4):e138312. https://doi.org/10.1172/jci.insight.138312.
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Research Article Metabolism Reproductive biology

Short-term Western-style diet negatively impacts reproductive outcomes in primates

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Abstract

A maternal Western-style diet (WSD) is associated with poor reproductive outcomes, but whether this is from the diet itself or underlying metabolic dysfunction is unknown. Here, we performed a longitudinal study using regularly cycling female rhesus macaques (n = 10) that underwent 2 consecutive in vitro fertilization (IVF) cycles, one while consuming a low-fat diet and another 6–8 months after consuming a high-fat WSD. Metabolic data were collected from the females prior to each IVF cycle. Follicular fluid (FF) and oocytes were assessed for cytokine/steroid levels and IVF potential, respectively. Although transition to a WSD led to weight gain and increased body fat, no difference in insulin levels was observed. A significant decrease in IL-1RA concentration and the ratio of cortisol/cortisone was detected in FF after WSD intake. Despite an increased probability of isolating mature oocytes, a 44% reduction in blastocyst number was observed with WSD consumption, and time-lapse imaging revealed delayed mitotic timing and multipolar divisions. RNA sequencing of blastocysts demonstrated dysregulation of genes involved in RNA binding, protein channel activity, mitochondrial function and pluripotency versus cell differentiation after WSD consumption. Thus, short-term WSD consumption promotes a proinflammatory intrafollicular microenvironment that is associated with impaired preimplantation development in the absence of large-scale metabolic changes.

Authors

Sweta Ravisankar, Alison Y. Ting, Melinda J. Murphy, Nash Redmayne, Dorothy Wang, Carrie A. McArthur, Diana L. Takahashi, Paul Kievit, Shawn L. Chavez, Jon D. Hennebold

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Figure 6

RNA-seq analysis of blastocysts reveals that short-term WSD consumption leads to changes in gene expression.

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RNA-seq analysis of blastocysts reveals that short-term WSD consumption ...
(A) A total of 13,167 genes were identified from the RNA-seq analysis of 31 blastocysts (n = 14 for SCD; n = 17 for WSD), out of which 1057 genes (5%) were differentially expressed. Of the differentially regulated genes (DEGs), 544 (~4% of the total number of genes and 51% of the DEGs) were significantly downregulated and 513 genes (~4% of the total number of genes and 49% of the DEGs) were significantly upregulated in the blastocysts obtained from animals receiving a WSD versus the blastocysts that were obtained from animals fed a SCD (*P < 0.05). (B) Principal component analysis (PCA) revealed 2 distinct populations of blastocysts representative of the samples obtained from COS #1 and COS #2 and denoted by dashed ovals. (C and D) The top gene ontology (GO) terms for molecular functions of the significantly upregulated (C) and significantly downregulated (D) genes are represented. The x axis is the negative log of the adjusted P value. (E) From the list of significantly DEGs, the top upregulated (16- to 32-fold) and downregulated (16- to 64-fold) genes in WSD blastocysts are shown. The x axis indicates the gene names, and the y axis represents the log2 fold change in gene expression. For C–E, the purple bars denote the upregulated genes, and the yellow bars indicate the downregulated genes. RNA-seq data P values were adjusted for multiple comparisons with the Benjamini-Hochberg method.

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