Environmental cadmium exposure induces fetal growth restriction via triggering PERK-regulated mitophagy in placental trophoblasts

Zhu, Hua-Long; Shi, Xue-Ting; Xu, Xiaofeng; Xiong, Yun; Yi, Song-Jia; Zhou, Guo-Xiang; Liu, Wei-Bo; Huang, Miaomiao; Gao, Lan; Zhang, Cheng; Zhao, Lingli; D, Xu; Wang, Hua

doi:10.1016/j.envint.2020.106319

Cited by 64 publications

(22 citation statements)

References 72 publications

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“…The placenta is a unique organ that provides nutrition and oxygen and plays a pivotal role in the maintenance of the developing fetus, we therefore first sought to test if the accumulation of RBC-NP-50 in placenta negatively impacted its functionality. Specifically, CYP11A1 and 3β-HSD that are involved in the steroid biosynthetic pathway in the placenta 25 were tested ( Figure 4A ). It was noted that mice have been treated by both 1HD and 3LD of RBC-NP-50 exhibited negligible impair against the expression of CYP11A1 and 3β-HSD in placenta, in comparison to controls.…”

Section: Resultsmentioning

confidence: 99%

Biocompatible Assessment of Erythrocyte Membrane-Camouflaged Polymeric PLGA Nanoparticles in Pregnant Mice: Both on Maternal and Fetal/Juvenile Mice

Chen¹,

Tian²,

Yang³

et al. 2022

IJN

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Purpose Poly(lactic- co -glycolic) acid (PLGA) nanoparticles coated with the membrane of red blood cells (RBC-NP) have been applied in various biomedical fields. Despite the well-documented great biocompatibility, the potential toxicity of RBC-NP on maternal mice or their developing fetuses during pregnancy, or juvenile mice post-birth, remains unclear, which warrants a systematic evaluation. Methods We fabricate an RBC-NP with approximately 50 nm in diameter (RBC-NP-50). Upon RBC-NP-50, pregnant mice are intravenously injected with this nanoparticle either at a single high dose of 400 mg/kg (1HD) or a low dose of 200 mg/kg for 3 times (3LD). Afterwards, the biocompatible assessments are performed at 48 h after the final injection or 21 d post-birth/partum both on maternal and fetal/juvenile mice. Results RBC-NP-50 is capable of accumulating in the placenta and then passing through the blood-fetal barrier (BFB) into the fetus. On 48 h after RBC-NP-50 exposure, no significant dose-dependent toxicity is observed in maternal mice including blood biochemistry, inflammatory factors, progesterone level, histological analysis, etc, whereas fetal brains reveal remarkable differentially expressed genes analyzed by transcriptome sequencing. On 21 d post-birth, those genes’ expression in juvenile mice is alleviated, along with negligible differences in behavioral evaluations including surface righting test, negative geotaxis test, cliff avoidance test, and olfactory orientation test. Conclusion These results indicate that RBC-NP is considered to be generally safe and biocompatible both for maternal mice and fetus during pregnancy, and for the subsequent juvenile mice post-birth, although future studies will need to examine higher dosage or longer-term measurements.

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Section: Resultsmentioning

confidence: 99%

Biocompatible Assessment of Erythrocyte Membrane-Camouflaged Polymeric PLGA Nanoparticles in Pregnant Mice: Both on Maternal and Fetal/Juvenile Mice

Chen¹,

Tian²,

Yang³

et al. 2022

IJN

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“…COX, encoded by dual genes in the nuclear and mitochondrial genomes, is closely related to energy metabolism. It is a key regulatory protein in the process of mitochondrial oxidative phosphorylation and respiration 38 . Changes in the mitochondrial respiratory chain marker protein COX IV can objectively reflect changes in mitochondrial content 39 .…”

Section: Discussionmentioning

confidence: 99%

“…It is a key regulatory protein in the process of mitochondrial oxidative phosphorylation and respiration. 38 Changes in the mitochondrial respiratory chain marker protein COX IV can objectively reflect changes in mitochondrial content. 39 Our results showed that the relative expression level of the mitochondrial marker protein COX IV significantly decreased with increasing FA exposure, suggesting that FA can cause a reduction in the mitochondrial content.…”

Section: Discussionmentioning

confidence: 99%

Study of the mechanism underlying the role of PINK1/Parkin in the formic acid‐induced autophagy of PC12 cells

Chen

Yan

et al. 2023

Basic Clin Pharma Tox

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This study aimed to explore PINK1/Parkin's role in methanol metabolite formic acid‐induced autophagy in PC12 cells and provide a theoretical basis for elucidating methanol‐induced neurotoxicity. After treatment with different formic acid concentrations, we observed the morphology and mitochondria of PC12 cells. We used an ultra‐micro enzyme kit to detect the mitochondrial Na+‐K+‐ATPase and Ca2+‐Mg2+‐ATPase activities; a JC‐1 kit to detect changes in the mitochondrial membrane potential (MMP); MDC staining to detect the autophagy levels; and western blotting to measure the expression levels of the mitochondrial marker protein COX IV and the autophagy‐related proteins Beclin1, P62 and LC3II/LC3I, and the mitochondrial and cytoplasmic levels of PINK1, Parkin and P‐Parkin. Compared with the control group, the mitochondrial diameters, the mitochondrial Na+‐K+‐ATP and Ca2+‐Mg2+‐ATPase activities, the MMP, and the COX IV expression levels decreased significantly (P < 0.05). The fluorescence signal intensity (indicating autophagy); relative Beclin1 and LC3II/LC3I protein expression levels; and relative mitochondrial PINK1, Parkin and P‐Parkin levels increased significantly, and the relative P62 protein expression levels and relative cytoplasmic PINK1, Parkin and P‐Parkin levels decreased significantly (P < 0.05) compared with the control group. Thus, formic acid alters mitochondrial morphology, causes mitochondrial dysfunction, affects the PINK/Parkin pathway and, thus, activates the process of mitochondrial autophagy.

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“…Epigenetics are another possible cause of FGR. Zhu et al designed a study to investigate whether cadmium (Cd) environmental toxicant and exposure induces the restriction of fetal growth by triggering PERK-regulated mitophagy in placental trophoblasts [ 85 ]. They used Cd as an environmental stressor to stimulate FGR in pregnant mice.…”

Section: Fetal Growth Restriction and Correlation With Mitophagymentioning

confidence: 99%

Mitochondrial Dysfunction, Mitophagy and Their Correlation with Perinatal Complications: Preeclampsia and Low Birth Weight

2022

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Mitochondria are essential organelles and crucial for cellular survival. Mitochondrial biogenesis and mitophagy are dynamic features that are essential for both maintaining the health of the mitochondrial network and cellular demands. The accumulation of damaged mitochondria has been shown to be related to a wide range of pathologies ranging from neurological to musculoskeletal. Mitophagy is the selective autophagy of mitochondria, eliminating dysfunctional mitochondria in cells by engulfment within double-membraned vesicles. Preeclampsia and low birth weight constitute prenatal complications during pregnancy and are leading causes of maternal and fetal mortality and morbidity. Both placental implantation and fetal growth require a large amount of energy, and a defect in the mitochondrial quality control mechanism may be responsible for the pathophysiology of these diseases. In this review, we compiled current studies investigating the role of BNIP3, DRAM1, and FUNDC1, mediators of receptor-mediated mitophagy, in the progression of preeclampsia and the role of mitophagy pathways in the pathophysiology of low birth weight. Recent studies have indicated that mitochondrial dysfunction and accumulation of reactive oxygen species are related to preeclampsia and low birth weight. However, due to the lack of studies in this field, the results are controversial. Therefore, mitophagy-related pathways associated with these pathologies still need to be elucidated. Mitophagy-related pathways are among the promising study targets that can reveal the pathophysiology behind preeclampsia and low birth weight.

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Environmental cadmium exposure induces fetal growth restriction via triggering PERK-regulated mitophagy in placental trophoblasts

Cited by 64 publications

References 72 publications

Biocompatible Assessment of Erythrocyte Membrane-Camouflaged Polymeric PLGA Nanoparticles in Pregnant Mice: Both on Maternal and Fetal/Juvenile Mice

Biocompatible Assessment of Erythrocyte Membrane-Camouflaged Polymeric PLGA Nanoparticles in Pregnant Mice: Both on Maternal and Fetal/Juvenile Mice

Study of the mechanism underlying the role of PINK1/Parkin in the formic acid‐induced autophagy of PC12 cells

Mitochondrial Dysfunction, Mitophagy and Their Correlation with Perinatal Complications: Preeclampsia and Low Birth Weight

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