Increased Circulating Cortisol After Vaginal Birth Is Associated With Increased FGF19 Secretion in Neonatal Pigs

Abstract

The influence of birth modality (scheduled cesarean or spontaneous vaginal) on the development of the newborn has been a source of controversy in neonatology. The impact of cesarean versus vaginal birth on the development of bile acid and FGF19 signaling is unknown. Our aim was to determine the effect of birth modality and gestational age (preterm vs. term) on plasma hormone levels, bile acid pool distribution, expression of genes in the bile acid-FXR-FGF19 pathway, and plasma levels of FGF19 at birth and on day 3 of life in neonatal pigs. Four sows underwent a cesarean section on gestation day 105 (n = 2) and 114 (n = 2; term = 115d), and two additional sows were allowed to farrow at term (gestation days 112 and 118). Piglets were euthanized at birth (Term-Vaginal n = 6; Term-Cesarean n = 8; Preterm n = 10) for tissue and blood collection, and the remaining pigs were nutritionally supported on total parenteral nutrition (TPN) then fed enterally on day 3 (Term-Vaginal n = 8; Term-Cesarean n = 10; Preterm n = 8), before blood and tissue were collected. Piglets born vaginally had a markedly (30-fold) higher plasma FGF19 at birth than term pigs born via cesarean section, and 70-fold higher than preterm pigs (p < 0.001). However, distal ileum FGF19 gene expression was similar in all groups (p > 0.05). Plasma FGF19 positively correlated with plasma cortisol (r = 0.58; p < 0.05) and dexamethasone treatment increased ileal FGF19 expression in cultured pig tissue explants and human enteroids. Our findings suggest that exposure to maternal or endogenous glucocorticoids in the perinatal period may upregulate the development of the bile-acid-FGF19 pathway.