Gestational nutrition 2: gene expression in sheep fetal ovaries exposed to gestational under nutrition

in Reproduction
Correspondence should be addressed to P Smith; Email:

A number of studies have demonstrated effects of gestational undernutrition on fetal ovarian development and postnatal female fertility. However, the mechanism underlying these effects remains elusive. Using a cohort of animals in which altered gestational nutrition affected indicators of postnatal fertility, this study applies RNAseq to fetal ovaries to identify affected genes and pathways that may underlie the relationship between gestational plane of nutrition and postnatal fertility. Pregnant ewes were exposed to either a maintenance diet or 0.6 of maintenance for the first 55 days of gestation followed by an ad libitum diet. Complementary DNA libraries were constructed from 5 to 6 fetal ovaries from each nutritional group at both days 55 and 75 of gestation and sequenced using Ion Proton. Of approximately 16,000 transcripts, 69 genes were differentially expressed at day 55 and 145 genes differentially expressed at day 75. At both gestational ages, genes expressed preferentially in germ cells were common among the differentially expressed genes. Enriched gene ontology terms included ion transport, nucleic acid binding, protease inhibitor activity and carrier proteins of the albumin family. Affected pathways identified by IPA analysis included LXR/RXR activation, FXR/RXR activation, pathways associated with nitric oxide production and citrullination (by NOS1), vitamin C transport and metabolism and REDOX reactions. The data offer some insights into potential mechanisms underlying the relationship between gestational plane of nutrition and postnatal fertility observed in these animals. In particular, the roles of nitric oxide and protease inhibitors in germ cell development are highlighted and warrant further study.

Downloadable materials

  • Supplementary Material
  • Supplementary Table : Comparison of fold changes detected by Nanostring and RNAseq


    Society for Reproduction and Fertility

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    Volcano plots illustrating fold change vs false discovery rate. (A) Day 55 genes and (B) day 75 genes. Differentially expressed genes (between nutritional groups) are represented by red dots. Genes not differentially expressed are represented by black dots.

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    Bland–Altman plot comparing fold changes obtained from Nanostring and RNAseq for 28 genes. Vertical axis represent mean fold change of the two techniques, horizontal axis represents the difference in fold change obtained from the two methodologies.


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