Abstract
Purpose Because thyroid hormones from the maternal thyroid glands are known to influence the growth, development, and metabolic functioning of offspring, we used a rat model to preliminarily investigate the effects of maternal hypothyroidism on glucose metabolism, pancreas cell proliferation, and insulin production in young male offspring and the possible underlying mechanisms. Methods Female rats were divided into a maternal hypothyroidism (MH) group, which received water containing 0.02% 6-propyl-2-thiouracil before and during pregnancy to induce hypothyroidism, and a control group which consumed tap water. Results Our results showed that there were no differences of islets structure between the offspring from the two groups, but glucose metabolism was impaired with higher plasma glucose concentrations at 0 and 15 min in the OGTT in 8-week-old offspring of the MH group. From birth to 8 weeks, pancreatic TRβ1 and TRβ2 mRNA level declined significantly in MH offspring, accompanied by decreased Ki67 and insulin mRNA expression. Conclusions Maternal hypothyroidism results in impaired pancreatic insulin synthesis and pancreatic cell proliferation in neonatal offspring and subsequent glucose intolerance in young offspring, which may be related to TRβ gene downregulation in the pancreas.
Highlights
Since the theory of fetal origins of adult disease (FOAD) was posed by Barker [1], much effort has been directed at understanding the relationship between maternal hypothyroidism and adult degenerative and metabolic diseases
The serum Thyroid-Stimulating Hormone (TSH) level of neonates born in the maternal hypothyroidism (MH) group was significantly higher than that in the control group (p < 0 05)
Our present study showed that hypothyroidism leads to reduced maternal weight gain during the gestational period and a prolonged gestational period
Summary
Since the theory of fetal origins of adult disease (FOAD) was posed by Barker [1], much effort has been directed at understanding the relationship between maternal hypothyroidism and adult degenerative and metabolic diseases. The relationship between maternal hypothyroidism and glucose metabolic abnormalities in adult offspring has been increasingly emphasized, with research in rats showing that maternal hypothyroidism causes IUGR and diminished insulin secretion capacity in adult offspring [6]. The maternal level of thyroid hormone is crucial for the development of β cells in offspring. Evidence showed that most effects of thyroid hormone are mediated by nuclear thyroid hormone receptors (TRs), including TRα and TRβ. They act as transcription factors [7, 8] and are abundantly expressed in pancreatic islets [9].
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