Perinatal undernutrition programmes thyroid function in the adult rat offspring

Abstract

Increasing evidence suggests that alterations in early nutrition programme physiological changes in adulthood. In the present study, we determined the effects of undernutrition during gestation and lactation on the programming of thyroid function in adult rat offspring. Perinatal undernutrition was achieved by a 40 % food restriction in female Wistar rats from the mating day to weaning. On postpartum day 21, the offspring of the control and food-restricted dams were weaned and given free access to a commercial diet until adulthood. The results showed that undernourished rats exhibited decreased 3,5,3 0 -triiodothyronine (T 3 ) levels but had normal thyroxine (T 4 ) and thyrotropin (TSH) levels at weaning; on day 90, these rats displayed a significant flip, exhibiting normalised T 3 (total and free) and total T 4 levels, but low free T 4 and persistently higher TSH levels, which were maintained even on postnatal day 140. This profile was accompanied by a scarce fat depot, a lower RMR and an exacerbated sympathetic brown adipose tissue (BAT) tone (deiodinase type 2 expression) in basal conditions. Moreover, when a functional challenge (cold exposure) was applied, the restricted group exhibited partial changes in TSH (29 v. 100 %) and T 4 (non-response v. 17 %) levels, a significant decrease in leptin levels (75 v. 32 %) and the maintenance of a sympathetic BAT over-response (higher noradrenaline levels) in comparison with the control group. The findings of the present study suggest that undernutrition during the perinatal period produces permanent changes in the hypothalamus -pituitary-thyroid axis with consequent low body weight and decreased RMR and facultative thermogenesis. We hypothesise that these changes predispose individuals to exhibiting adult subclinical hypothyroidism.

Neonatal Maternal Separation Alters, in a Sex-Specific Manner, the Expression of TRH, of TRH-Degrading Ectoenzyme in the Rat Hypothalamus, and the Response of the Thyroid Axis to Starvation

“…Many of the molecules critical for HPT axis activity are indeed regulated by TH, but they could also be modulated by other hormones, such as CORT or leptin (22, 47, 48, 64 -66). Nutritional interventions as overfeeding or food restriction during the lactation period, or mother´s malnutrition can affect the expression of several elements involved in the activity of the HPT axis (67)(68)(69). Indirect effects on the development of TRHergic neurons may also occur by defects in their innervations since projections from the arcuate nucleus do not reach the PVN until the second postnatal week, and those arising from the brain stem until the end of the third week (65,70).…”

Role of omega‐6 and omega‐3 fatty acids in fetal programming

“…These effects may be sex‐specific, as maternal malnutrition during early gestation increased body mass index (BMI) and waist circumference in 50‐year‐old women but not in men . These findings have been replicated in rodent models, showing that maternal undernutrition programmes severe glucose intolerance and β‐cell dysfunction, dysfunctional skeletal muscle energetics, abnormal mitochondrial function in the heart and changes in the hypothalamus‐pituitary‐thyroid (HPT) axis in offspring …”

“…12 These findings have been replicated in rodent models, showing that maternal undernutrition programmes severe glucose intolerance and β-cell dysfunction, 13 dysfunctional skeletal muscle energetics, 14 abnormal mitochondrial function in the heart 15 and changes in the hypothalamus-pituitary-thyroid (HPT) axis in offspring. 16 Human studies have also demonstrated adverse impacts of maternal overnutrition and obesity in fetal programming. A case-control study performed at Trondheim University Hospital, Norway, suggested that maternal obesity leads to myocardial dysfunction in offspring.…”

Hypothyroid offspring replacement with euthyroid wet nurses during lactation improves thyroid programming without modifying metabolic programming

“…Several experiments in animal models have shown that nutrition (3), hormone-regulated metabolism (4,5), and other toxic influences such as thyroid disruptors affect metabolic and thyroid programming (6). In these conditions, adaptive metabolic strategies in the offspring change the metabolic set points in order to permit survival under critical conditions (7); for example, malnutrition in lactating rats was associated with changes in body weight (3,8) and thyroid dysfunction in their adult offspring (9).…”