Administration of Thyroxine Affects the Morphometric Parameters and VEGF Expression in the Uterus and Placenta and the Uterine Vascularization but does Not Affect Reproductive Parameters in Gilts During Early Gestation

Abstract

The aim of this study was to evaluate the effects of thyroxine administration on morphometric parameters, expression of vascular endothelial growth factor (VEGF) and vascularization in the uterus and placenta and reproductive parameters in gilts at 70 days of gestation. At 150 days of age, i.e., before first heat, 20 gilts were randomly divided into two experimental groups: treated (n=10) and control (n=10). The treated group received a daily dose of 400 μg of L-thyroxine (T(4)) in their diet until slaughter and the control group received only typical meals. Before artificial insemination, blood was collected to determine plasma total T(4). The gilts were inseminated in the second oestrus and slaughtered at 70 days of gestation. The foetal thyroid follicular epithelium height, number, size and weight of foetuses; foetal myogenesis, corpora lutea number, embryonic mortality rate, uterine weight, placental weight and placental fluid volume were measured. Histomorphometric and immunohistochemical analysis of uterus and placenta were determined. The averages of all variables were compared by the Student's t-test. The gilts treated with thyroxine showed significant increase of plasma total T(4). At 70 days of gestation, the heights of the trophoblastic epithelium, endometrial epithelium and endometrial gland epithelium were significantly higher in the group treated with T(4). The expression of cytoplasmatic and nuclear VEGF in trophoblastic cells and the number of blood vessels per field in endometrial stroma were significantly higher in the gilts treated with T(4). No other significant differences between groups were obtained with respect to other parameters (p>0.05). We conclude that oral administration of T(4) up to 70 days of pregnancy in gilts affects the morphometric parameters, the expression of placental VEGF and the uterine vascularization but does not affect reproductive parameters in gilts during early gestation.

Maternal thyroid dysfunction affects placental profile of inflammatory mediators and the intrauterine trophoblast migration kinetics

“…The changes observed in this study in the placental immunological profile in animals with hypothyroidism and excess of T 4 mirror, at least in part, the fetal-placental changes seen in women and in animals with thyroid dysfunction (Shafrir et al 1994, Morrish et al 1997, Galton et al 2001, Freitas et al 2007, Souza et al 2011, Silva et al 2012. Our study also confirmed the hypothesis of Silva et al (2012) that the migration of trophoblast cells is affected by thyroid dysfunction, particularly in hypothyroidism.…”

“…However, several of the pathological processes observed in hypothyroidism may result from changes in the placental pro-and anti-inflammatory cytokine profile (Koga et al 2009). In contrast, hyperthyroidism increases reproductive efficiency in experimental animal models (Serakides et al 2001, Freitas et al 2007 and causes significant changes in the uterine vasculature (Souza et al 2011) and in the proliferation of trophoblast cells (Freitas et al 2007). It is important to mention that placental changes similar to those observed in hypo-and hyperthyroidism may also be influenced by the migration kinetics of the trophoblast cells (Knöfler 2010, Hammer 2011, Chakraborty et al 2011, Soares et al 2012.…”

Maternal thyrotropin is independently related to Small for Gestational Age neonates at term

“…studied the role of thyroid hormones in placentation and found no association. However, there is some evidence that high FT3 and FT4 levels do have a role in vascularization, proliferation and differentiation of the placenta . A recent meta‐analysis on levothyroxine treatment in women with subclinical hypothyroidism undergoing assisted reproductive techniques has indicated that T4‐replacement therapy is beneficial on pregnancy outcomes, possibly indicating a role for thyroid hormones on placentation as well …”

In Vitro Study on the Regulation of Annexin IV and VEGF by hCG in the Human Endometrium

“…VEGF and its receptor regulate vascular permeability [ 29 ]. Meanwhile, changes in vascular permeability are involved in the maturation of the endometrium and the implantation window [ 30 , 31 ]. Hosper et al [ 32 ] showed that VEGF presents regular periodic changes on the uterus during the menstrual cycle.…”