Effect of birth rank, and placentome subtype on expression of genes involved in placental nutrient transport in sheep

Placental function is a key determinant of fetal growth and development that can be influenced by maternal and fetal environmental factors. The molecular mechanisms by which the placenta senses and responds to environmental cues are poorly understood. This exploratory study aimed to characterize the effect of birth rank (single vs. twin) and placentome morphologic subtype on expression of genes involved in nutrient transport, angiogenesis, immunity and stress response. Cotyledonary tissue was collected from type A, B and C placentomes from five single and six twin fetuses at 140 days of gestation. GLUT1 and GLUT3 were the most highly expressed genes consistent with the high demand for glucose to support fetal growth. Expression of BCKDHβ and IGF-2 was 1.3- and 1.5-fold higher, respectively, and PCYT1A was 3-fold lower in singles compared to twins (P < 0.05) while no other differences in gene expression were observed between birth ranks. Expression of EAAT2 and LAT2 was higher while PCYT1A was lower in A compared to B type cotyledons. Expression of GUCY1B1/3 and IGF-1 was higher while CD98 and LAT2 were lower in type B compared to C cotyledons (P < 0.05). Compared to type C cotyledons, expression of EAAT2, IGF-1, IGF-2, LAT1 was higher, while TEK was lower in type A cotyledons. The effects of birth rank on placental gene expression in this study indicated that placental nutrient transport and/or function differs between single and twin pregnancies in sheep. Differences in gene expression between the placentome subtypes suggests that changes in placentome morphology are associated with shifts in amino acid transport and metabolism, oxidative stress and angiogenesis and/or blood flow. This study highlights that placental gene expression differs in response to birth rank and placentome morphologic subtype which suggests that both maternal and fetal factors may influence placental function in sheep. These associations provide insights into gene pathways for more targeted future investigations as well as potential adaptations to improve placental efficiency to support fetal growth in twin pregnancies.