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

Cordeiro

et al. 2023

IJMS

Self Cite

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.

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

Cordeiro

et al. 2023

IJMS

Self Cite

“…This study firstly reported that high levels of TPOAb may be associated with elevated placental oxidative stress cytokines. An animal study had shown that hypothyroidism decreased the expression of HO-1, GRP78 and C/EBP homologous protein (CHOP) genes/proteins in the mid-gestation while increased the expression of HIF-1α, CHOP and nuclear factor erythroid 2-related factor 2 (NRF2) genes/proteins ( 15 ). HO-1 is a crucial cytokine for immune tolerance and promotes the establishment of an anti-inflammatory environment ( 56 ).…”

Section: Discussionmentioning

confidence: 99%

“…This may be linked to inflammatory mediators in the placenta. At present, there is only evidence from animal studies suggesting that hypothyroidism affects maternal immune function by interfering with the development of an anti-inflammatory environment, and that maternal hypothyroidism is associated with hypoxia and activation of inflammatory and oxidative stress at the maternal-fetal interface ( 14 , 15 ). Hypothyroidism reduced the expression of placental interferon-γ (IFN-γ), IL-10 and migration inhibitory factor (MIF) in rats ( 14 ), which stimulates the expression of a wide variety of pro-inflammatory cytokines ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

Association of maternal thyroid peroxidase antibody during pregnancy with placental morphology and inflammatory and oxidative stress responses

Ru,

Yang,

Teng

et al. 2023

Front. Endocrinol.

BackgroundStudies suggest that thyroid peroxidase antibody (TPOAb) positivity exposure during pregnancy may contribute to changes in placental morphology and pathophysiology. However, little is known about the association of maternal TPOAb during pregnancy with placental morphology and cytokines. This study focuses on the effect of repeated measurements of maternal TPOAb during pregnancy on the placental morphology and cytokines.MethodsBased on Ma’anshan Birth Cohort (MABC) in China, maternal TPOAb levels were retrospectively detected in the first, second and third trimesters. Placental tissues were collected 30 minutes after childbirth, placental morphological indicators were obtained by immediate measurement and formula calculation, and cytokine mRNA expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR) afterward. Generalized linear models and linear mixed models were analyzed for the relationships of maternal TPOAb in the first, second and third trimesters with placental indicators.ResultsTotally 2274 maternal-fetal pairs were included in the analysis of maternal TPOAb levels and placental morphology, and 2122 pairs were included in that of maternal TPOAb levels and placental cytokines. Maternal TPOAb levels in early pregnancy were negatively associated with placental length, thickness, volume, weight and disc eccentricity, while positively correlated with placental IL-6, TNF-α, CRP, CD68, MCP-1, IL-10, HO-1, HIF-1α and GRP78. In mid-pregnancy, maternal TPOAb levels were negatively correlated with placental length, width and area. In late pregnancy, maternal TPOAb levels were negatively correlated with placental length, area, volume and weight. Repeated measures analysis showed that maternal TPOAb positivity tended to increase placental TNF-α, CD68 and MCP-1 while decreasing placental length, width and area than TPOAb negativity. Repeated measures analysis showed that maternal TPOAb levels were positively correlated with placental IL-6, TNF-α, CD68, MCP-1, IL-10, HO-1, HIF-1α and GRP78, while negatively correlated with placental length, area, volume, weight, and disc eccentricity.ConclusionThere may be trimester-specific associations between maternal TPOAb levels and placental morphology and inflammatory and oxidative stress responses. The effect of maternal TPOAb levels on placental morphology is present throughout pregnancy. Early pregnancy may be the critical period for the association between maternal TPOAb levels and placental inflammatory and oxidative stress responses.

Journal of Feline Medicine and Surgery

“…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

Self Cite

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.