The Relationship Between Heavy Metals and Missed Abortion: Using Mediation of Serum Hormones.

Accumulating evidence suggests that heavy metal exposure may have adverse effects on the fetal development. Furthermore, disruption of serum hormone homeostasis can result in the adverse pregnancy outcomes. Therefore, this study aimed to investigate the potential association between heavy metals and missed abortion, with a focus on whether serum hormones mediate this relationship. The concentrations of heavy metals and hormones in serum were measured in this case-control study. Statistical models including, logistic regression model, principal component analysis (PCA), and weighted quantile sum (WQS) regression model were employed to examine the relationship between heavy metals, serum hormones, and missed abortion. Furthermore, the mediation analysis was performed to assess the role of serum hormones as potential mediators in this relationship. This study revealed significant associations between heavy metal exposure and missed abortion. Notable, the WQS index weight, which was mainly influenced by copper (Cu) and zine (Zn), is associated with missed abortion. Moreover, heavy metals including manganese (Mn), nickel (Ni), Zn, arsenic (As), Cu, cadmium (Cd), and lead (Pb) were found to be associated with serum levels of ß-human chorionic gonadotropin (ß-hCG), progesterone (P), estradiol (E2), and lactogen (HPL). In addition, the mediation analysis indicated that ß-hCG explained a portion of the association (ranging from 18.77 to 43.51%) of between Mn, Ni, Zn, and As exposure and missed abortion. Serum P levels explained 17.93 to 51.70% of the association between Ni, Cu, and As exposure and missed abortion. Serum E2 levels played a significant mediating role, explaining a portion of the association (ranging from 22.14 to 73.60%) between Mn, Ni, Cu, As, Cd, and Pb exposure and missed abortion. Our results suggested that ß-hCG, P, and E2 are one of the potential mediators in the complex relationship between heavy metals exposure and missed abortion. These results highlight the importance of considering both heavy metal exposure and serum hormone levels in understanding the etiology of missed abortion.

In missed abortion the decrease of IGF-1 down-regulates PI3K/AKT signaling pathway reducing the secretion of progesterone and ß-hCG.

OBJECTIVE: To explore whether the reduction of IGF-1 in missed abortion down-regulates PI3K/AKT signaling pathway, thereby causing trophoblast cell apoptosis and reducing the secretion of ß-hCG and progesterone. DESIGN: 12 pairs of serum and villous tissues were selected from missed abortion patients and normal early pregnant women who had terminated pregnancy by artificial abortion. The subjects in two groups had same age and gestational week. Wes Simple Western system and qRT-PCR were used to detect the expression of IGF-1, IGF-1R, PI3K/AKT signaling pathway and apoptosis-related factors in villous tissues. Radioimmunoassay and Enzyme-linked immunosorbent assay were used to detect ß-hCG, progesterone and IGF-1 in serum. RESULTS: The serum levels of ß-hCG, progesterone and IGF-1 were decreased in missed abortion group than those in normal early pregnant women. In addition, compared with normal early pregnant women, the genes and proteins levels of IGF-1 and PI3K/AKT signaling pathway and anti-apoptosis related factors were significantly decreased. CONCLUSIONS: Our results suggested that the reduction of IGF-1 in missed abortion patients could down-regulate the expression of PI3K/AKT signaling pathway, thereby increasing the apoptosis of trophoblast cells, leading to decreased secretion of ß-hCG and progesterone, which may be one of the important mechanisms of missed abortion.

The role of ß-HCG and VEGF-MEK/ERK signaling pathway in villi angiogenesis in patients with missed abortion.

OBJECTIVE: To analyze the effects of the Human Chorionic Gonadotropin beta (ß-hCG) and the VEGF-MEK/ERK signaling pathway on villi angiogenesis in early missed abortion. METHODS: A total of 12 cases of women with missed abortion and 12 cases of women who had induced abortion voluntarily without any disease were included in the present study. The age, pregnancy time and gestation period in the control group corresponded to the missed abortion group. Wes Simple Western system and qRT-PCR were used to detect the expression of VEGF-MEK/ERK signaling pathway related proteins and genes in villous. Radioimmunoassay and Enzyme-linked immunosorbent assay were used to detect ß-hCG and VEGF levels in serum. The microvascular density (MVD) in villous tissue was analyzed by immunohistochemical staining. RESULTS: The levels of ß-hCG and VEGF in serum, the expression of VEGF-MEK/ERK signaling pathway and MVD in villous tissue of the missed abortion group were lower than those of the control group. In addition, compared with the control group, the layers of trophoblasts of the villous tissue in the missed abortion group became thinner significantly, the number of cells reduced, the cell structures were disorganized, and parts of the trophoblast cells were absent. Correlational analysis showed that the protein expression of ERK1/2 was positively correlated with MVD in missed abortion group. CONCLUSIONS: Our results reveal that decreased production of ß-hCG in early pregnant women could down-regulate the expression of VEGF-MEK/ERK signal pathway, then reduce angiogenesis and eventually leading to the abnormal angiogenesis of villous, which may be an important mechanism of missed abortion.

Apigenin attenuates acrylonitrile-induced neuro-inflammation in rats: Involved of inactivation of the TLR4/NF-κB signaling pathway.

Acrylonitrile (ACN) is often found in the productions of synthetic fibers, rubber, and plastics. Exposure to ACN could cause pathological changes of the nervous system, which appeared early and were very serious. Current studies have found that the neurotoxicity is mainly related to oxidative damage and inflammation induced by ACN. Apigenin (AP) is a flavonoid subtype compound that is less toxic, non-mutagenic, and widely distributed in many types of vegetables and fruits. Studies have confirmed that it has nice antioxidant, anti-inflammatory and anti-apoptotic properties in the nervous system and related disease models, such as Alzheimer's disease. In this study, we used AP (117, 234 and 351 mg·kg-1) pretreatment intragastrically to resist the neurotoxicity caused by ACN gavage (46 mg·kg-1) for 28 days, and then detected the oxidative stress, inflammation mediated by the TLR4/NF-κB signaling pathway, and apoptosis to evaluate the protective effect of AP. The results showed that AP could lessen the autonomic activities of rats, and improve the abnormal morphology of neurons induced by ACN. AP could also reduce the oxidative stress, downregulate the TLR4/NF-κB signaling pathway, decrease the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and inhibit the mitochondria-mediated neuron apoptosis. Immunofluorescence result showed that AP could decrease the activation and nuclear transfer of NF-κB induced by ACN. These results suggested that AP could protect the brain against ACN-induced neurotoxicity by inhibiting the TLR4/NF-κB signaling pathway and could exhibit a neuroprotective effect.