Early Levothyroxine Treatment on Maternal Subclinical Hypothyroidism Improves Spatial Learning of Offspring in Rats

Abstract

Maternal hypothyroidism has adverse effects on neural development in the offspring. The present study aimed to investigate whether maternal subclinical hypothyroidism impairs spatial learning in the offspring, as well as the efficacy and optimal time of levothyroxine (L-T(4)) treatment in pregnancy. Female adult Wistar rats were randomly divided into six groups (n = 10 per group): control, hypothyroid (H), subclinical hypothyroid (SCH) and SCH treated with L-T(4), starting from the tenth, thirteenth and seventeenth gestational day (GD10, GD13 and GD17), respectively, to restore normal thyroid hormone levels. Spatial learning was assessed on progenies by a water maze test, a field excitatory postsynaptic potential (fEPSP) recording, and an long-term potentiation induction assay. Protein levels of early growth response protein 1 (Egr1), activity-regulated cytoskeleton-associated protein (Arc), Ras-proximate-1 (Rap1), p-extracellular signal-regulated kinase (p-ERK) and brain-derived neurotrophic factor (BDNF) were determined by western blotting. Progenies from the SCH and H groups demonstrated significantly longer mean latency in the water maze test and a lower amplification percentage of the amplitude and slope of the fEPSPs compared to offspring of the control group. L-T(4) treatment for the GD10 and GD13 groups significantly shortened mean latency and increased the amplification percentage of the amplitude and slope of the fEPSPs of the progeny of rats with subclinical hypothyroidism. However, L-T(4) treatment for the GD17 group showed only minimal effects on spatial learning in the offspring. Progenies of SCH and H groups had lower levels of Egr1, Arc, p-ERK and BDNF but higher levels of Rap1 compared to those of the controls. L-T(4) treatment ameliorated these protein expression changes in the progeny of rats with subclinical hypothyroidism. Maternal subclinical hypothyroidism impaired spatial learning in the offspring; L-T(4) treatment in early pregnancy recovered this adverse effect, and the optimal time of treatment should start from early pregnancy (GD10 and GD13).

Effect of maternal excessive iodine intake on neurodevelopment and cognitive function in rat offspring

“…Previous reports have documented that maternal thyroid dysfunction could affect the expression of BDNF and cause neurological defects in neonates [40] and adult rats [11]. Our previous studies [10,41] reported that maternal subclinical hypothyroidism decreased BDNF expression in rat pup hippocampi and impaired spatial learning; pups required more time during the Morris water maze test to find the hidden platform, compared with pups from NI mothers. The present study found that BDNF protein levels were decreased in the hippocampi of the pups from both the 3HI and LI mothers.…”

Pregnancy Outcomes among Obese Pregnant Women with Hypothyroidism: Medical Record Review of a Single Tertiary Center in Saudi Arabia

“…Currently the benefits of treatment with levothyroxine for women with hypothyroidism during pregnancy remain controversial. The results of meta-analysis of randomized control trials revealed that Levothyroxine (LT4) therapy significantly reduced the miscarriage rate, gestational diabetes, and gestational hypertension, but not preeclampsia [25]. Moreover, the study found that LT4 group had fewer preterm deliveries, birth weights <2500 g, deaths, and congenital malformations compared to control group in regards to neonatal outcomes [25].…”

“…The results of meta-analysis of randomized control trials revealed that Levothyroxine (LT4) therapy significantly reduced the miscarriage rate, gestational diabetes, and gestational hypertension, but not preeclampsia [25]. Moreover, the study found that LT4 group had fewer preterm deliveries, birth weights <2500 g, deaths, and congenital malformations compared to control group in regards to neonatal outcomes [25]. A recent study showed that LT4 therapy is associated with a reduced risk of low birth weight (LBW) offspring and a low Apgar score among women with subclinical hypothyroidism [26].…”

Exposure of pregnant mice to triclosan impairs placental development and nutrient transport

“…These doses were chosen based on a recent report that mice exposed to 10 mg/kg TCS exhibited urinary TCS levels equivalent to those of spontaneous abortion patients5. Levothyroxine (T4) (Sigma-Aldrich Inc., St. Louis, MO, USA) was dissolved in 0.9% saline solution and injected (20 μg/kg/day) subcutaneously (s.c.)44. The mTOR inhibitor rapamycin (Sigma-Aldrich Inc., St Louis, MO, USA) and the PI3K inhibitor LY294002 (Sigma-Aldrich Inc., St. Louis, MO, USA) were dissolved in 0.9% saline solution.…”