Placental Transcriptome Adaptations to Maternal Nutrient Restriction in Sheep

Area of Science:

• Reproductive Biology
• Developmental Biology
• Genomics

Background:

• Maternal nutrient restriction (NR) impacts placental development and fetal growth.
• Placental transcriptome alterations are key to understanding fetal growth disparities under NR.

Purpose of the Study:

• To investigate placentome transcriptome changes in response to maternal nutrient restriction (NR) at mid-pregnancy (day 70) and late-pregnancy (day 135).
• To identify specific genes and pathways affected in fetuses with normal growth (NR NonSGA) and small for gestational age (NR SGA) under NR conditions.

Main Methods:

• Pregnant sheep were fed 100% or 50% of NRC recommendations (NR) from day 35 to 135.
• Placentomes were analyzed at day 70 and 135.
• Gene expression analysis and Gene Set Enrichment Analysis (GSEA) were performed on NR SGA, NR NonSGA, and control (100% NRC) groups.

Main Results:

• At day 70, significant gene dysregulation was observed between NR SGA, NR NonSGA, and control groups.
• Genes involved in MHC class II protein binding, signaling receptor binding, and cytokine activity were affected.
• GSEA revealed enrichment of natural killer cell-mediated cytotoxicity genes in NR SGA placentomes and altered nutrient utilization pathways between NR SGA and NR NonSGA groups.

Conclusions:

• Novel factors associated with impaired placental function in small for gestational age (SGA) fetuses under NR were identified.
• Placentomes from NR NonSGA pregnancies demonstrate adaptive potential to nutritional hardship.
• These findings provide insights into placental adaptation and dysfunction during nutrient-restricted pregnancies.