Endocrine Abstracts

Background: Recent studies in France have shown a 1.4-fold increase in the incidence of congenital hypothyroidism (CH) due to gland in situ over the last four decades. CH was previously thought to follow a monogenic model. In recent years, however, evidence has emerged for a more complex genetic cause involving multiple genes and external factors. Our hypothesis is that environmental factors such as endocrine disrupting chemicals (EDCs) may lead to altered thyroid development and function during prenatal and postnatal life. Approximately 30 anthropogenic chemicals have been identified in American women, 15 of which are ubiquitous, including in pregnant women. A mixture of these 15 EDCs affects thyroid hormone signaling and thus early brain development in the Xenopus model. In addition, the human foetus is also exposed to sodium fluoride (NaF), which crosses the placental barrier and has been recognized as an EDC. This latter does cause a reduction in thyroid hormone secretion, but the underlying mechanism remains unknown.

Objectives: Study the effects of long-term exposure to EDC on thyroid function before mating and throughout the life of the mice.

Methods: Parental exposure two weeks before mating and offspring exposure from birth to 10 months of age to EDC mixture and EDC-NaF mixture. The thyroid phenotype was analyzed and compared with phenotype of unexposed mice, taking into account the sex difference male/female. Histological sections of thyroid glands were performed at adult stage (1 month and 10 months) to analyze tissue structures and size. Quantitative PCR was performed to look for disturbances in the expression of thyroid transcription markers, differentiation markers and oxidative stress markers.

Results: In exposed female mice to EDC-NaF, the thyroid gland was significantly 20% smaller than in non-exposed females (P < 0.05). In addition, increased expression of Pax8, Nkx2-1, Foxe1, Nis, Tg, Duox2, Dio1 and Dio2 expression was observed in the thyroid suggesting an hyperactivity of the gland (P < 0.05). The male thyroid gland showed a decrease in Tpo at 1 month and a strong increase in Dio2 and Nox4, respectively by a factor of 3 and 2 (P < 0.01) at 10 months, indicating oxidative stress.

Conclusions: Exposure to EDC leads to long-term thyroid dysfunction with a strong difference between males and females. Actions of NaF and EDC were potentialized in female mice thyroids. Action of EDC mixture in males gave a strong impact on oxidative stress. Further studies are needed to elucidate the exact mechanism of these disturbances in two sexes.