Fetal growth restriction in hypothyroidism is associated with changes in proliferative activity, apoptosis and vascularisation of the placenta

Silva, Juneo Freitas; Vidigal, Paula N; Galvão, Daniele D; Boeloni, Jankerle Neves; Nunes, Philipe Pimenta; Ocarino, Natália de Melo; Nascimento, Evaldo; Serákides, Rogéria

doi:10.1071/rd11219

Cited by 52 publications

(42 citation statements)

References 38 publications

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“…The reduction in this area can affect the proper development of the placenta (Ashkar & Croy 1999). This change could be involved in the genesis of low birth weight and placental changes observed in rats with hypothyroidism and in rats treated with the same PTU doses used in this present study (Silva et al 2012).…”

Section: Discussionmentioning

confidence: 84%

“…The hypothyroid group received 1 mg/animal PTU 10 diluted in 5ml distilled water by orogastric gavage daily (Silva et al 2004, Silva et al 2012). Rats treated with T 4 received 50µg/animal/day L-thyroxine 11 (Serakides et al 2001, Freitas et al 2007) diluted in 5ml distilled water by orogastric gavage daily.…”

Section: Methodsmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

“…Maternal hypothyroidism is known to result in low birth weight and placental abnormalities (Silva et al 2012). By contrast, hyperthyroidism promotes an increase in the birth rate without affecting weight or fetal viability (Freitas et al 2007).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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A putative adverse outcome network for neonatal mortality and lower birth weight in rodents: Applicability to per‐ and polyfluoroalkyl substances and relevance to human health

Rogers

Heintz

Thompson

et al. 2023

Birth Defects Research

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Background Some per‐ and poly‐fluoroalkyl substances (PFAS) cause neonatal mortality and lower birth weight in rodents. We constructed an Adverse Outcome Pathway (AOP) network for neonatal mortality and lower birth weight in rodents, comprising three putative AOPs. We then assessed strengths of the evidence for the AOPs and applicability to PFAS. Finally, we considered the relevance of this AOP network to human health. Methods Literature searches targeted PFAS, peroxisome proliferator‐activated receptor (PPAR) agonists, other nuclear receptors, relevant tissues, and developmental targets. We used reviews of established biology and described results of studies with prenatal PFAS exposure that assessed birth weight and neonatal survival. Molecular initiating events (MIEs) and key events (KEs) were proposed and strengths of KE relationships (KERs), applicability to PFAS, and human relevance were assessed. Results Neonatal mortality has been observed in rodents following gestational exposure to most longer chain PFAS studied, often coincident with lower birth weight. In AOP 1, PPARα activation and PPARγ activation or downregulation are MIEs; placental insufficiency, fetal nutrient restriction, neonatal hepatic glycogen deficit, and hypoglycemia are KEs leading to neonatal mortality and lower birth weight. In AOP 2, constitutive androstane receptor (CAR) and pregnane X receptor (PXR) activation upregulates Phase II metabolism, lowering maternal circulating thyroid hormones. In AOP 3, disrupted pulmonary surfactant function and PPARγ downregulation cause neonatal airway collapse and mortality from respiratory failure. Conclusions It is likely that different components of this AOP network will apply to different PFAS, largely determined by which nuclear receptors they activate. The MIEs and KEs in this AOP network can occur in humans, but differences in PPAR structure and function, and the timeline of liver and lung development, suggest that humans may be less susceptible to this AOP network. This putative AOP network elucidates knowledge gaps and research needed to better understand the developmental toxicity of PFAS.

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Intermittent Fasting and Vitamin E Supplementation Attenuates Hypothyroidism‐Associated Ophthalmopathy

Kumar,

Das,

Kumari

et al. 2024

Molecular Nutrition Food Res

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Visualization is a complex‐integrated procedure of the eyes and brain that allows to see this colorful world. Hypothyroidism‐associated ophthalmopathy (HAO), often known as dry eyes, swelling around the eyes, blurred vision, glaucoma, and cataracts, are some eye‐related issues caused by hypothyroidism. Yet there is no permanent cure for hypothyroidism; taking medicine throughout life is the only solution to keep its harmful effects under control. This study used intermittent fasting (IF) and vitamin E (Vit.E) supplementation to prevent hypothyroidism‐associated ophthalmopathy. This study hypothesized that intermittent fasting‐like diet regimens and vitamin supplementation should reduce the propagation of HAO by its antioxidant potential. In the present study, experimental animals are divided into five groups: normal, hypothyroidism control, dual, Vit. E, and IF. Hypothyroidism is generated in the experimental groups by taking propylthiouracil (PTU) for 24 days while also taking IF and Vit. E supplements. The hypothyroid‐induced experimental animals demonstrated an increase in IOP and lipid peroxidation while thyroid hormone levels depicted a massive decline which is a clear denotation of the effects of the thyroid on eyes and lifestyle. Ancient Ayurveda inspires these proposed therapies and has successfully reduced all the damage to the thyroid gland and the eye.

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Fetal growth restriction in hypothyroidism is associated with changes in proliferative activity, apoptosis and vascularisation of the placenta

Cited by 52 publications

References 38 publications

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

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

A putative adverse outcome network for neonatal mortality and lower birth weight in rodents: Applicability to per‐ and polyfluoroalkyl substances and relevance to human health

Intermittent Fasting and Vitamin E Supplementation Attenuates Hypothyroidism‐Associated Ophthalmopathy

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