Hyperthyroidism advances luteolysis in the pregnant rat through changes in prostaglandin balance

Navas, Paola B.; Motta, Alicia Beatriz; Hapon, María Belén; Jahn, Graciela A.

doi:10.1016/j.fertnstert.2011.07.010

Cited by 15 publications

(13 citation statements)

References 41 publications

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“…We suggest that the increased gene and protein expression of MIF and INFy in T 4 -treated animals at 19 days of gestation may be related to the preterm delivery observed in these animals (Navas et al 2011). Delivery is characterized by an influx of inflammatory cells into the myometrium (Koga et al 2009).…”

Section: Discussionmentioning

confidence: 89%

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

Silva¹,

Ocarino²,

Serákides³

2014

Reproduction

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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.

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Section: Discussionmentioning

confidence: 89%

“…The lower endovascular trophoblast invasion observed in the T 4 -treated rats at 18 days of gestation may also be related to the premature delivery observed in these animals (Navas et al 2011). This may be explained by the occurrence of death and/or removal of invasive trophoblast cells during and after delivery (Soares et al 2012).…”

Section: Discussionmentioning

confidence: 89%

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

Silva¹,

Ocarino²,

Serákides³

2014

Reproduction

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“…Furthermore, previous studies have shown that the reduction of placental VEGF expression below physiological levels is related to preterm births in women (Kramer et al 2005, Chaiworapongsa et al 2009, Andraweera et al 2012. One hypothesis is that the reduction of VEGF and Flk-1 in the decidua and metrial gland of rats with excess T 4 is one of several mechanisms that can operate to trigger early delivery in hyperthyroid rats (Navas et al 2011).…”

Section: Discussionmentioning

confidence: 99%

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

Souza

Silva

Silva³

et al. 2017

Pesq. Vet. Bras.

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RESUMO.-[Hormônios tireoidianos afetam a decidualização e a angiogênese na decídua e glândula metrial de ratas.] Este estudo teve como objetivo avaliar os efeitos dos hormônios tireoidianos sobre a decídua e a glândula metrial pela análise da expressão de fatores angiogênicos em ratas. 72 ratas adultas, fêmeas foram distribuídas nos grupos hipotiroideo, tratado com T 4 e controle. Aos 10, 14 e 19 dias de gestação (DG), a decídua e a glândula metrial foram coletadas para avaliação histomorfométrica e imunoistoquímica da expressão de VEGF, Flk-1 e Tie-2. O hipotireoidismo reduziu a área da decídua aos 10 e 19 DG. Além disso, o VEGF aumentou aos 10 e 14 DG e o Flk-1 apenas aos 14 DG, mas ambos foram reduzidos aos 19 DG na glândula metrial sem alterar significativamente a área ocupada pelos vasos sanguíneos. As ratas tratadas com T 4 apresentaram aumento do número de vasos sanguíneos na decídua aos 10 e 19 DG. Além disso, aos 10 DG, o excesso de T 4 resultou no aumento de Flk-1 na decídua e na glândula metrial. O hipotireoidismo aumentou o Tie-2 em 10 e 19 DG na decídua e na glândula metrial. Desta forma, pode-se concluir que o hipotireoidismo reduz a área da decídua e aumenta a expressão de VEGF, Tie-2 e Flk-1. O excesso de T 4 promove a angiogênese tecidual ao aumentar o número de vasos na decídua devido ao aumento da expressão de Flk-1. , and control groups. At 10, 14 and 19 days of gestation (DG), the decidua and metrial gland were collected for histomorphometric and immunohistochemical evaluation of the expression of VEGF, Flk-1 and Tie-2. Hypothyroidism reduced the area of the decidua at 10 and 19 DG. Furthermore, VEGF was increased at 10 and 14 DG, and Flk-1 only at 14 DG, but both was reduced at 19 DG in the metrial gland without significantly changing the area occupied by blood vessels. Rats treated with T 4 showed an increase in the decidua blood vessels at 10 and 19 DG. However, at 10 DG, excess T 4 resulted in increased of Flk-1 in the decidua and metrial gland. Hypothyroidism increased the Tie-2 at 10 and 19 DG in the decidua and metrial gland. In conclusion, hypothyroidism reduces the area of the decidua and increases the expression of VEGF, Tie-2 and Flk-1. The excess of T 4 promotes tissue angiogenesis by increasing the number of vessels in the decidua because of the increased expression of Flk-1.INDEX TERMS: Thyroid hormones, decidualization, angiogenesis, decidua, metrial gland, rats. thyroxine, PTU. 1003 Thyroid hormones affect decidualization and angiogenesis in the decidua and metrial gland of rats

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“…Wada et al [56] also observed a reduction of the luteal blood flow at the end of the pregnancy period in mice before any of the structural changes of luteal regression. As hyperthyroid animals undergo an early luteal regression [29], one hypothesis is that a hypoxic environment has already been developed in the corpus luteum of these animals at 19 days of gestation, justifying the higher expression of VEGF and Flk-1 in relation to control animals.…”

Section: Discussionmentioning

confidence: 99%

“…The PGF2α has luteolytic and vasoactive activities in the corpus luteum [19]. We believe that the changes in the duration of the luteal phases of pregnant animals with hypo- or hyperthyroidism [25-29] can also be a result of changes in COX-2 expression and, consequently, in the expression of prostaglandins.…”

Section: Introductionmentioning

confidence: 99%

Luteal activity of pregnant rats with hypo-and hyperthyroidism

2014

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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.

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Hyperthyroidism advances luteolysis in the pregnant rat through changes in prostaglandin balance

Cited by 15 publications

References 41 publications

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

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

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

Luteal activity of pregnant rats with hypo-and hyperthyroidism

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