Luteal activity of pregnant rats with hypo-and hyperthyroidism

Juneo Freitas Silva,Rogéria Serakides,Natália Melo Ocarino

doi:10.1186/1757-2215-7-75

Juneo Freitas Silva, Rogéria Serakides + Show 1 more

Open Access

https://doi.org/10.1186/1757-2215-7-75

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Abstract

BackgroundLuteal activity is dependent on the interaction of various growth factors, cytokines and hormones, including the thyroid hormones, being that hypo- and hyperthyroidism alter the gestational period and are also a cause of miscarriage and stillbirth. Because of that, we evaluated the proliferation, apoptosis and expression of angiogenic factors and COX-2 in the corpus luteum of hypo- and hyperthyroid pregnant rats.MethodsSeventy-two adult female rats were equally distributed into three groups: hypothyroid, hyperthyroid and control. Hypo- and hyperthyroidism were induced by the daily administration of propylthiouracil and L-thyroxine, respectively. The administration began five days before becoming pregnant and the animals were sacrificed at days 10, 14, and 19 of gestation. We performed an immunohistochemical analysis to evaluate the expression of CDC-47, VEGF, Flk-1 (VEGF receptor) and COX-2. Apoptosis was evaluated by the TUNEL assay. We assessed the gene expression of VEGF, Flk-1, caspase 3, COX-2 and PGF2α receptor using real time RT-PCR. The data were analyzed by SNK test.ResultsHypothyroidism reduced COX-2 expression on day 10 and 19 (P < 0.05), endothelial/pericyte and luteal cell proliferation on day 10 and 14 (p < 0.05), apoptotic cell numbers on day 19 (p < 0.05) and the expression of Flk-1 and VEGF on day 14 and 19, respectively (p < 0.05). Hyperthyroidism increased the expression of COX-2 on day 19 (P < 0.05) and the proliferative activity of endothelial/pericytes cells on day 14 (p <0.05), as well as the expression of VEGF and Flk-1 on day 19 (P < 0.05).ConclusionsHypothyroidism reduces the proliferation, apoptosis and expression of angiogenic factors and COX-2in the corpus luteum of pregnant rats, contrary to what is observed in hyperthyroid animals, being this effect dependent of the gestational period.

Highlights

Luteal activity is dependent on the interaction of various growth factors, cytokines and hormones, including the thyroid hormones, being that hypo- and hyperthyroidism alter the gestational period and are a cause of miscarriage and stillbirth
Induction of thyroid dysfunction The induction of hypo-and hyperthyroidism during the entire period of the pregnancy was confirmed by serum free T4 at days 0 and 19 of gestation
Proliferative activity Regardless of the experimental group, the Cell division control protein 47 (CDC-47) immunohistochemical expression in the corpus luteum was more intense at 14 days of gestation compared to other gestational periods (Figure 2)

Summary

Introduction

Luteal activity is dependent on the interaction of various growth factors, cytokines and hormones, including the thyroid hormones, being that hypo- and hyperthyroidism alter the gestational period and are a cause of miscarriage and stillbirth. We evaluated the proliferation, apoptosis and expression of angiogenic factors and COX-2 in the corpus luteum of hypo- and hyperthyroid pregnant rats. Luteal activity is dependent on the interaction of various growth factors, cytokines and hormones, including the thyroid hormones [4]. Hypo- and hyperthyroidism in rats alter the gestational period, causing prolonged gestation and preterm births, respectively [4]. One hypothesis of this study is that one of the mechanisms by which thyroid dysfunctions affects pregnancy is by altering the proliferative and apoptotic activities of the corpus luteum. CDC47 is essential for initiation of DNA replication [15], while caspase-3 is required for DNA fragmentation and some of the typical morphological changes of cells undergoing apoptosis [16]

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