Trophoblast migration and invasion through the decidua and maternal uterine spiral arteries are crucial events in placentation. During this process, invasive trophoblast replace vascular endothelial cells as the uterine arteries are remodeled to form more permissive vessels that facilitate adequate blood flow to the growing fetus. Placentation failures resulting from either extensive or shallow trophoblastic invasion can cause pregnancy complications such as preeclampsia, intrauterine growth restriction, placenta creta, gestational trophoblastic disease and even maternal or fetal death. Consequently, the use of experimental animal models such as rats and mice has led to great progress in recent years with regards to the identification of mechanisms and factors that control trophoblast migration kinetics. This review aims to perform a comparative analysis of placentation and the mechanisms and factors that coordinate intrauterine trophoblast migration in humans, rats and mice under physiological and pathological conditions.

Thyroid hormones are vital for the proper functioning of the female reproductive system, since they modulate the metabolism and development of ovarian, uterine and placental tissues. Therefore, hypo- and hyperthyroidism may result in subfertility or infertility in both women and animals. Other well-documented sequelae of maternal thyroid dysfunctions include menstrual/estral irregularity, anovulation, abortion, preterm delivery, preeclampsia, intrauterine growth restriction, postpartum thyroiditis, and mental retardation in children. Several studies have been carried out involving prospective and retrospective studies of women with thyroid dysfunction, as well as in vivo and in vitro assays of hypo- and hyperthyroidism using experimental animal models and/or ovarian, uterine and placental cell culture. These studies have sought to elucidate the mechanisms by which thyroid hormones influence reproduction to better understand the physiology of the reproductive system and to provide better therapeutic tools for reproductive dysfunctions that originate from thyroid dysfunctions. Therefore, this review aims to summarize and update the available information related to the role of thyroid hormones in the morphophysiology of the ovary, uterus and placenta in women and animals and the effects of hypo- and hyperthyroidism on the female reproductive system.

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-T4)-treated rats. A total of 144 adult female rats were divided equally into hypothyroid, l-T4-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 γ (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 (Tnfα)), 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). T4-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 T4-treated group (P<0.05). Excess of T4 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 T4 differentially affect the immune profile and the intrauterine trophoblast migration of the placenta, and these effects are dependent on the gestational period.

The objective of this study was to evaluate fetal weight, histomorphometric changes and proliferative activity, apoptosis and angiogenesis of the placenta in rats with hypothyroidism. Thirty-six adult female rats were divided into two groups with 18 animals each: control and hypothyroidism. Hypothyroidism was induced by daily administration of propylthiouracil (1 mg/animal). The administration began five days before becoming pregnant and the animals were sacrificed at 14 or 19 days of gestation. The control group received a placebo. The number and weight of fetuses and the rate of fetal death was determined, as well as the morphometric characteristics, the immunohistochemical expression of cell division control protein 47 (CDC)-47 and vascular endothelial growth factor (VEGF) and the number of apoptotic cells in the placental disk. The data were analysed by Mann–Whitney U test. Hypothyroidism reduced the weight of fetuses and of the uterus and placenta (P < 0.05), altered the thickness of the placental labyrinth and spongiotrophoblast (P < 0.05), increased the population of glycogen cells in the spongiotrophoblast (P < 0.05), interfered with the vascular development of the placental labyrinth and decreased VEGF expression (P < 0.05), reduced the expression of CDC-47 and cellularity and increased the apoptotic rate in the placental disk (P < 0.05). We conclude that hypothyroidism affects fetal weight by altering the proliferative activity, apoptosis and vascularisation of the placenta.