Fetal over- and undernutrition differentially program thyroid axis adaptability in adult sheep

Abstract

ObjectiveWe aimed to test, whether fetal under- or overnutrition differentially program the thyroid axis with lasting effects on energy metabolism, and if early-life postnatal overnutrition modulates implications of prenatal programming.DesignTwin-pregnant sheep (n = 36) were either adequately (NORM), under- (LOW; 50% of NORM) or overnourished (HIGH; 150% of energy and 110% of protein requirements) in the last-trimester of gestation. From 3 days-of-age to 6 months-of-age, twin lambs received a conventional (CONV) or an obesogenic, high-carbohydrate high-fat (HCHF) diet. Subgroups were slaughtered at 6-months-of-age. Remaining lambs were fed a low-fat diet until 2½ years-of-age (adulthood).MethodsSerum hormone levels were determined at 6 months- and 2½ years-of-age. At 2½ years-of-age, feed intake capacity (intake over 4-h following 72-h fasting) was determined, and an intravenous thyroxine tolerance test (iTTT) was performed, including measurements of heart rate, rectal temperature and energy expenditure (EE).ResultsIn the iTTT, the LOW and nutritionally mismatched NORM:HCHF and HIGH:CONV sheep increased serum T3, T3:T4 and T3:TSH less than NORM:CONV, whereas TSH was decreased less in HIGH, NORM:HCHF and LOW:HCHF. Early postnatal exposure to the HCHF diet decreased basal adult EE in NORM and HIGH, but not LOW, and increased adult feed intake capacity in NORM and LOW, but not HIGH.Conclusions: The iTTT revealed a differential programming of central and peripheral HPT axis function in response to late fetal malnutrition and an early postnatal obesogenic diet, with long-term implications for adult HPT axis adaptability and associated consequences for adiposity risk.

Hierarchies in the energy budget: Thyroid hormones and the evolution of human life history patterns

“…Given that the fetus relies heavily on maternal thyroid hormone, it is possible that maternal thyroid hormone dynamics may influence the offspring's phenotype through developmental programming. 120 Rae et al found that when pregnant sheep were fed a low-calorie diet, tT3 concentrations were significantly lower in both maternal and fetal plasma. 121 The authors raise the possibility that thyroid hormones may play a role in mediating the effects of maternal undernutrition on fetal development.…”

Frontiers in sheep reproduction - making use of natural responses to environmental challenges to manage productivity

“…h) 'Programming' future reproductive performance -from gamete to embryo to fetus The concept of 'Developmental Origins of Health and Disease' (DoHaD) began with the epidemiology of maternal undernutrition in humans and was then extended to farm animals (review: Sinclair et al, 2016). There is now strong evidence for 'programming' of diverse aspects of future health and productivity in sheep (Figure 2) -eg, the quantity and quality of wool, milk and meat produced (eg, Kelly et al, 2006;van der Linden et al, 2009;Sen et al, 2015); cardiovascular health, salt tolerance, thyroid function, and glucose homeostasis (Gopalakrishnan et al, 2004;Chadwick et al, 2009;Jaquiery et al, 2016;Johnsen et al, 2018). Interestingly, the DoHaD hypothesis began with a focus on the fetus but has now been extended back to before fertilization because there is evidence that undernutrition also causes effects in the oocyte and embryo that have consequences for postnatal life (Ashworth et al, 2009;Jaquiery et al, 2012).…”

The Effects of Developmental Programming upon Neonatal Mortality

“…As fetal thyroid gland differentiates between 75 and 90 dpc, maternal dietary restriction during early-gestation may reset the physiology of the HPT axis by altering ontogeny of the thyroid 71 . This is reflected in increased free T3 (FT3) levels in the neonatal calf 10 and lamb 72 .…”