Impaired invasion of EVTs results in inadequate remodelling of arteries and poor placentation, leading to PE. TMBIM4 was found to promote the migration and invasion of human osteosarcoma U2-OS and breast cancer MCF7 cell lines. However, the effect of TMBIM4 on trophoblast biological behaviour and its relevance to PE pathophysiology remain unclear. In this study, we confirmed that TMBIM4 was highly expressed in cytotrophoblasts, syncytiotrophoblasts, and EVTs of the human placenta during early pregnancy. By comparing the expression levels of TMBIM4 in the placenta of women with normal-term pregnancy and PE, TMBIM4 was found to be significantly decreased in PE. Thereafter, we determined the expression of TMBIM4 in the LPS-treated first-trimester human trophoblast cell line HTR-8/SVneo (mimicking a PE-like cell model), and determined the effect of TMBIM4 on trophoblast function and its underlying mechanism. LPS treatment reduced the expression of TMBIM4 and induced NLRP3 inflammasome activity in HTR-8/SVneo cells. KO of TMBIM4 in the HTR-8/SVneo cell line impaired cell viability, migration, and invasion, which was more severe in the LPS/ATP-treated TMBIM4-KO cell line. Moreover, TMBIM4 deficiency enhanced NLRP3 inflammasome activity and promoted subsequent pyroptosis, with or without LPS/ATP treatment. The negative relationship between TMBIM4 expression and NLRP3 inflammatory activity was verified in PE placentas. Inhibiting the NLRP3 inflammasome with MCC950 in HTR-8/SVneo cells alleviated LPS/ATP-induced pyroptosis and damaged cell function in the TMBIM4-KO cell line. Overall, this study revealed a new PE-associated protein, TMBIM4, and its biological significance in trophoblast pyroptosis mediated by the NLRP3 inflammasome. TMBIM4 may serve as a potential target for the treatment of placental inflammation-associated PE.

To explore the association of gestational diabetes mellitus (GDM) with maternal and neonatal adverse outcomes among women with advanced maternal age. This retrospective cohort study included 1551,140 eligible pregnant women from the National Vital Statistics System database in 2017 to 2019, and all participants were divided into two groups: GDM group (n = 154,646) and non-GDM group (n = 1396,494). Univariate and multivariate logistic regression analyses were used to assess the association of GDM and maternal and neonatal outcomes; additionally, we also adopted subgroup analysis to analyze the association in detail based on gestational weight gain (GWG) levels. The risk of each adverse outcome was presented by using odds ratio (OR) and 95% confidence interval (CI). After adjusted some covariables, GDM increased the risk of neonatal assisted ventilation (OR = 1.380, 95% CI: 1.345–1.417), neonatal intensive care unit (NICU, OR = 1.436, 95% CI: 1.410–1.463) admission, neonatal low Apgar score at the fifth minutes (OR = 1.034, 95% CI: 1.018–1.051), neonatal high birth weight (OR = 1.132, 95% CI: 1.111–1.153), neonatal premature birth (OR = 1.244, 95% CI: 1.223–1.266), mothers entered intensive care unit (ICU, OR = 1.247, 95% CI: 1.107–1.406), and mothers took cesarean section (OR = 1.193, 95% CI: 1.180–1.207) among women with advanced maternal age. The study findings indicated that GDM was the risk factor for obstetric outcomes among women with advanced maternal age, which will have important implications for the management of GDM in women with advanced maternal age.

PE is a life‐threatening pregnancy disorder that can lead to adverse events for both the fetus and the mother. Autophagy is a cellular process involved in cellular renovation and maintaining homeostasis. There is a growing body of evidence suggesting that autophagy in trophoblasts plays a significant role in the development and pathogenesis of PE. However, the exact mechanisms are not yet fully understood. This article provides an overview of recent evidence regarding the role of autophagy in trophoblast invasion, vascular remodelling, inflammation, immune response, and maternal factors in the context of PE. It is believed that impaired or excessive autophagy can contribute to placental ischaemia and hypoxia, thereby exacerbating PE progression. Therefore, understanding the molecular mechanisms that regulate autophagy in PE is crucial for the development of targeted therapeutic interventions in the future.