Nutritional restriction during late gestation disrupts placental transcriptional programs related to metabolism, transport, and immune function in a sheep model.

BACKGROUND: Studies on the effects of nutrition on the placenta mainly focus on early to middle pregnancy due to rapid fetal development during this period. In late gestation, although nutrient restriction has been linked to adverse fetal outcomes and altered uteroplacental physiology, the placental transcriptional programs that coordinate substrate transport, metabolic adaptation, and immune-related pathways under maternal undernutrition remain incompletely characterized, particularly in large-animal models. Therefore, this study aims to characterize transcriptional alterations associated with placental metabolism, nutrient transport, and immune regulation in response to nutritional restriction during late pregnancy.

RESULTS: In this study, late-gestation ewes were restricted to 30% feeding levels for 15 days to establish an undernourished sheep model. Results indicated that nutritional restriction during late pregnancy didn't affect placental weight and cotyledon number but reduced placental efficiency. Nutritional restriction lowered placental carbohydrate metabolism and altered amino acid metabolism, thereby increasing glucose and essential amino acid levels and decreasing non-essential amino acid levels in the umbilical cord blood (UCB). Nutritional restriction disrupted ubiquitination and the proteinase and suppressed transcription factors, collagen formation, cell adhesion and migration, and capillary genesis in the placenta from male fetuses. Placental complement pathways were inhibited by nutritional restriction, indicating the weakened immune function.

CONCLUSIONS: This study revealed that nutritional restriction affects placental function in many ways, subsequently influencing fetal growth and development, which provides a basis for future research on the fetal.