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

Abstract

The objective of the present study was to evaluate the gene and immunohistochemical expression of inflammatory mediators involved in the immune activity and the intrauterine trophoblast migration of the placentas in hypothyroid and L-thyroxine (L-T 4 )-treated rats. A total of 144 adult female rats were divided equally into hypothyroid, L-T 4 -treated, and euthyroid (control) groups. Hypothyroidism was induced by daily administration of propylthiouracil. Rats were killed at 0, 10, 14, 15, 16, 17, 18, and 19 days of gestation. We evaluated the depth of interstitial and endovascular intrauterine trophoblast invasion and the immunohistochemical expression of interferon g (INFy), migration inhibitory factor (MIF), and inducible nitric oxide synthase (NOS2 (iNOS)). The gene expression of Toll-like receptor 2 (Tlr2) and Tlr4, Infy, Mif, tumor necrosis factor (Tnf (Tnfa)), Il10, Nos2, matrix metalloproteinase 2 (Mmp2) and Mmp9, and placental leptin was also measured in placental disks by real-time RT-PCR. The data were analyzed using an Student-Newman-Keuls (SNK) test. Hypothyroidism reduced the endovascular and interstitial trophoblast migration, and the expression of TLR4, INFy, MIF, interleukin 10 (IL10), NOS2, MMP2 and MMP9, and placental leptin, while increased the expression of TLR2 (P!0.05). T 4 -treated rats not only increased the expression of IL10 and NOS2 but also reduced the expression of TNF and MIF at 10 days of gestation (P!0.05). However, at 19 days of gestation, expression of INFy and MIF was increased in T 4 -treated group (P!0.05). Excess of T 4 also increased the gene expression of Mmp2 at 10 days of gestation (P!0.05), but reduced the endovascular trophoblast migration at 18 days of gestation (P!0.05). Hypothyroidism and excess of T 4 differentially affect the immune profile and the intrauterine trophoblast migration of the placenta, and these effects are dependent on the gestational period.

Maternal lithium chloride exposure alters the neuroendocrine‐cytokine axis in neonatal albino rats

“…These variations could have been the result of the hypothyroidism in dams and neonates and have caused a metabolic syndrome. In parallel, hypothyroidism disrupts the release of cytokine during development (Ahmed, Abdel‐Latif, & Ahmed, ; De Vito et al, ; Silva et al, ) and causes metabolic diseases (Hugo et al, ). However, the complex interplay between these markers during development and the action of lithium require further study.…”

“…Furthermore, lithium can initiate brain disorders, coma, seizures, neural toxicity (Ahmad, Elnakady, Farooq, & Wadaan, ; Aral & Vecchio‐Sadus, ; Bartha, Marksteiner, Bauer, & Benke, ) and epilepsy (Xiao et al, ) via disrupting the levels of Serotonin (5‐HT) (Ayano, ; Stahl, ; Yadav et al, ), Dopamine (DA) (Malhi, ; McFarlane et al, ; O’Donnell & Gould, ) and Norepinephrine (NE) (De Bartolomeis, Tomasetti, Cicale, Yuan, & Manji, ; Sastre, Nicolay, Bruguerolle, & Portugal, ; Schildkraut, Logue, & Dodge, ). Interestingly, thyroid disorders can perturb the production of cytokines (Ahmed, Abdel‐Latif, & Ahmed, ; De Vito et al, ; Silva, Ocarino, & Serakides, ), causing brain disorders during growth/development (Andersen, Andersen, Vestergaard, & Olsen, ; O'Shaughnessy et al, , ; Thompson et al, ). However, studies of possible toxicological effects of LiCl on the neonatal neuroendocrine‐cytokine axis are scarce.…”

Thyroid hormones affect decidualization and angiogenesis in the decidua and metrial gland of rats

“…Furthermore, from 14 DG, the decidua begins its regression (Picut et al 2009). Another important factor observed by Silva et al (2014) was the reduction of trophoblastic invasion of the maternal-fetal interface occurred in hypothyroid rats. Reduced intrauterine trophoblastic migration results in impaired vascular remodeling, hypoxia and placental stress (Lala & Chakraborty 2003, Plaisier 2011, James et al 2012.…”

“…The decidua influences the entire process of placentation (Galton et al 1999, Galton et al 2001. Therefore, we hypothesized that the placental disc changes observed in rats with thyroid dysfunction (Silva et al 2012, Silva et al 2014, Silva et al 2015 might reflect changes in the decidua and metrial gland.…”

“…Hypothyroid rats exhibit compromised vasculature of the placental labyrinth and reduced trophoblastic expression of VEGF and its receptor Flk-1 by the end of pregnancy. Furthermore, there is a reduction in the expression of inducible nitric oxide synthase (iNOS) 9 and intrauterine trophoblastic migration, which are important for vasodilation and intrauterine vascular remodeling (Silva et al 2012, Silva et al 2014, Silva et al 2015. Silva et al (2015) observed that hyperthyroidism reduces VEGF and Flk-1 expression in trophoblast cells at the end of pregnancy, which suggests that such changes might be related to preterm delivery that is exhibited by these rats (Kramer et al 2005, Freitas et al 2007, Andraweera et al 2012.…”