Gestational age and fetal hypothyroidism Alter the porcine thyroid and local hepatic and renal renin‐angiotensin systems

This study was conducted to examine the ontogeny of and interactions between the thyroid system and local renin-angiotensin systems (RAS) in the porcine fetus. N = 24 pregnant gilts were split into two groups, receiving either a daily dose of methimazole to induce fetal hypothyroidism, or a daily sham control. Within each group, treatment of n = 3 gilts was initiated at gestational day 34, 45, 55, or 65, and terminated 21 days later to allow for fetal sample collection. The morphology of the fetal thyroid was assessed via lectin staining, showing that follicular structure changes with both increasing gestational age and altered thyroid status. Subsequently, the ontogeny of thyroid and RAS-related genes in the fetal liver and kidney, as well as the effect of fetal hypothyroidism, was assessed via qPCR. In the liver, SERPINA7, TTR, THRA, and THRB were all ontogenically regulated, with THRB also ontogenically regulated in the kidney. All studied RAS genes were ontogenically regulated in at least one of the studied tissues. Hypothyroidism caused temporal dysregulations in the expression of hepatic SERPINA7, AGT, ACE, ACE2, and AGTR2, as well as renal THRB, ACE, and AGTR1. These results suggest a temporal and tissue-dependent relationship between the thyroid and RAS in the fetal pig.