Maternal hypothyroidism causes oxidative stress and endoplasmic reticulum stress in the maternal-fetal interface of rats

Cordeiro, Jeane Martinha dos Anjos; Santos, Luciano Cardoso; Oliveira, Lisa; Santos, Bianca Reis; Santos, Emilly Oliveira; Barbosa, Erikles Macêdo; Macêdo, Isabela Oliveira de; Freitas, Gustavo José Cota de; Santos, Daniel de Assis; Lavor, Mário Sérgio Lima de; Silva, Juneo Freitas

doi:10.1016/j.freeradbiomed.2022.08.033

Cited by 11 publications

(3 citation statements)

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“…The activation of this pathway results from the activation of pattern recognition receptors (PRR), mainly toll-like receptors (TLRs), as well as cellular stress [ 37 , 38 ]. Therefore, we suggest that activation of this pathway in the animals of the present study may be associated with the increased placental expression of Tlr2 demonstrated in hypothyroid rats [ 12 ], as well as the oxidative stress, endoplasmic reticulum stress, and immune dysregulation observed in the maternal-fetal interfaces of these animals [ 12 , 15 , 33 ]. Although the activation of the inflammasome caused by hypothyroidism has been previously described in cardiac tissue, with increased protein expression of NLRP3 and Caspase 1 [ 44 ], this is the first study to describe inflammasome complex activation in decidual and placental dysfunction caused by maternal hypothyroidism.…”

Section: Discussionmentioning

confidence: 93%

“…Women with maternal hypothyroidism have an increased risk of miscarriage, premature birth, placental abruption, preeclampsia, gestational diabetes, and intrauterine growth restriction [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ], while in hypothyroid female rats the placental development is compromised, with alteration of immunology and trophoblastic endocrine function [ 7 , 9 , 10 , 11 , 12 , 13 , 14 ]. In addition, a recent study demonstrated that maternal hypothyroidism also causes oxidative stress and endoplasmic reticulum stress at the maternal-fetal interface of rats [ 15 ], suggesting that this cellular stress may result from the failure of intrauterine trophoblastic migration observed in these animals [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Kisspeptin Suppresses Inflammasome-NLRP3 Activation and Pyroptosis Caused by Hypothyroidism at the Maternal-Fetal Interface of Rats

Santos

Cordeiro

Santos

et al. 2023

IJMS

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Gestational diseases such as preeclampsia and gestational diabetes cause inflammasome activation and pyroptosis in the placenta and changes in placental kisspeptin levels. Although maternal hypothyroidism also reduces the kisspeptin/Kiss1R system at the maternal-fetal interface, there is still no information on whether this dysfunction causes inflammasome activation and pyroptosis in the placenta or influences the modulatory role of kisspeptin in these processes. This study aimed to evaluate whether hypothyroidism activates the inflammasome-NLRP3 pathway and pyroptosis at the maternal-fetal interface of rats and whether kisspeptin can modulate these processes. Hypothyroidism was induced in Wistar rats by the administration of propylthiouracil. Kisspeptin-10 (Kp10) treatment began on the 8th day of gestation (DG). Gene and/or protein expressions of NLRP3, Caspase 1, IL-1β, IL-18, and Gasdermin D (Gsmd) were evaluated in the deciduae and placentae at the 18th DG. Hypothyroidism increased the decidual and placental stainings of NLRP3, IL-1β, and Gasdermin D, and increased the gene expressions of Nlrp3, Ilβ, and Il18 in the placenta and of Gsmd in the decidua. Treatment with Kp10 suppressed the increase in NLRP3/Nlrp3, IL-1β, Il18, and Gasdermin D/Gsmd caused by hypothyroidism at the maternal-fetal interface. However, Kp10 increased the placental gene expressions of Casp1 and Il1β. The findings demonstrated that maternal hypothyroidism activated the inflammasome-NLRP3 pathway and pyroptosis at the maternal-fetal interface of rats and that treatment with Kp10 was able to block these processes, thus suggesting that kisspeptin analogues may be promising in the treatment of gestational diseases that involve inflammasome activation and pyroptosis.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Kisspeptin Suppresses Inflammasome-NLRP3 Activation and Pyroptosis Caused by Hypothyroidism at the Maternal-Fetal Interface of Rats

Santos

Cordeiro

Santos

et al. 2023

IJMS

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“…Since there was an imbalance in the uterine expression of GPX1 and catalase in the uterus of cats with pyometra, we evaluated whether this disease causes oxidative stress in the uterus by evaluating the immunostaining of 8OHdG, a biomarker of endogenous oxidative DNA damage. 21,30 The analysis showed that endometrial and myometrial immunostaining of 8OHdG was higher in cats with pyometra compared with healthy cats in dies trus (P <0.05) (Figure 4a-c).…”

Section: Pyometra Causes Oxidative Stress In the Uterus Of Catsmentioning

confidence: 97%

Pyometra alters the redox status and expression of estrogen and progesterone receptors in the uterus of domestic cats

Nascimento,

Santos,

Santos

et al. 2023

Journal of Feline Medicine and Surgery

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Objectives The aim of this study was to evaluate the expression profile of sex steroid receptors and redox mediators in the uterus of domestic cats with pyometra. Methods Twelve cats were used and divided into groups: (1) non-gestational healthy diestrus (n = 7) and (2) pyometra (n = 5). The plasma profiles of estradiol and progesterone (P4) as well as uterine expression levels of estradiol alpha (ERα), progesterone (PR) and androgen (AR) receptors, of the antioxidant enzymes superoxide dismutase 1 (SOD1), catalase and glutathione peroxidase 1 (GPX1), and of the oxidative damage marker 8-hydroxy-2′-deoxyguanosine (8-OHdG) were evaluated. Results Cats with pyometra showed higher plasma P4 levels and increased uterine messenger RNA (mRNA) and protein expression of ERα and PR, mainly in the glandular epithelium for ERα and in stromal and myometrial cells for PR. In addition, there was an increase in 8-OHdG immunostaining and GPX1 mRNA and protein expression in cats with pyometra compared with those in non-gestational diestrus, while catalase showed a reduction in endometrial immunostaining in cats with pyometra. There were no differences in uterine AR and SOD1 expression between the groups. Conclusion and relevance The findings of this study showed that pyometra is associated with oxidative stress in the uterus of domestic cats and alterations of the profile of sex steroid receptors, especially ERα and PR, and of antioxidant enzymes, suggesting that changes in these mediators may play a role with the etiopathogenesis of this disease.

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Ameliorative effects of thiamin on learning behavior and memory dysfunction in a rat model of hypothyroidism: implication of oxidative stress and acetylcholinesterase

Saberi,

Mirazi,

Amirahmadi

et al. 2023

Metab Brain Dis

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Maternal hypothyroidism causes oxidative stress and endoplasmic reticulum stress in the maternal-fetal interface of rats

Cited by 11 publications

References 77 publications

Kisspeptin Suppresses Inflammasome-NLRP3 Activation and Pyroptosis Caused by Hypothyroidism at the Maternal-Fetal Interface of Rats

Kisspeptin Suppresses Inflammasome-NLRP3 Activation and Pyroptosis Caused by Hypothyroidism at the Maternal-Fetal Interface of Rats

Pyometra alters the redox status and expression of estrogen and progesterone receptors in the uterus of domestic cats

Ameliorative effects of thiamin on learning behavior and memory dysfunction in a rat model of hypothyroidism: implication of oxidative stress and acetylcholinesterase

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