Exposure to benzo[a]pyrene impairs decidualization and decidual angiogenesis in mice during early pregnancy

Li, Xueyan; Shen, Cha; Liu, Xueqing; He, Junlin; Ding, Yubin; Gao, Rufei; Mu, Xinyi; Geng, Yanqing; Wang, Yingxiong; Chen, Xuemei

doi:10.1016/j.envpol.2016.11.029

Cited by 47 publications

(21 citation statements)

References 50 publications

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“…Down-regulated miR-hz04 activated murine IP 3 R 1 /Camk2g/Sgcb pathway in pregnant mice with BaPinduced miscarriage Environmental BaP exposure might be one of the causes for the unexplained miscarriage. Then, a mouse model was made in which pregnant mice were treated with 0, 0.05, or 0.2 mg/kg BaP to induce miscarriage [41] [42]. BaP could be metabolized to ultimately carcinogenic BPDE in mice.…”

Section: Hz04mentioning

confidence: 99%

WITHDRAWN: Novel lncRNA-HZ04 Promotes BPDE-Induced Human Trophoblast Cell Apoptosis and Miscarriage by Up-Regulating IP3R1/CaMKII/SGCB Pathway by Competitively Binding with miR-hz04

Huang

Dai

Mi³

et al. 2020

Preprint

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BackgroundMiscarriage seriously hinders human reproduction. BaP (benzo(a)pyrene) and its metabolite BPDE (benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide) could cause trophoblast cell dysfunctions and might further induce human miscarriage. However, the underlying mechanisms remain largely unknown. ResultsHerein, we identified a novel lnc-HZ04 up-regulated and a novel miR-hz04 down-regulated in the unexplained recurrent miscarriage (RM) villous tissues relative to the healthy control tissues and also in the BPDE-exposed trophoblast cells. Lnc-HZ04 served as competing endogenous RNA (ceRNA), directly and specifically bound with miR-hz04 on its target site, and diminished the inhibition effects of miR-hz04 on IP3R1 mRNA expression level and its mRNA stability, thus activated Ca2+-mediated IP3R1/p-CaMKII/SGCB apoptosis pathway, which further promoted trophoblast cell apoptosis. The miR-hz04 target site, but not its mutant, on lnc-HZ04 played important roles in these regulations. In normal trophoblast, relatively less lnc-HZ04 and more miR-hz04 inhibited this apoptosis pathway and gave normal pregnancy. After exposure to BPDE or in the RM tissues, relatively more lnc-HZ04 and less miR-hz04 activated this apoptosis pathway and induced miscarriage. BaP could also induce mice miscarriage by up-regulating this corresponding murine apoptosis pathway. ConclusionsThis work discovered that lnc-HZ04 served as a ceRNA for miR-hz04 and up-regulated IP3R1/CaMKII/SGCB pathway, which promoted the BPDE-induced human trophoblast cell apoptosis and the occurrence of miscarriage, providing novel scientific and clinical understanding in the occurrence of unexplained miscarriage.

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Section: Hz04mentioning

confidence: 99%

WITHDRAWN: Novel lncRNA-HZ04 Promotes BPDE-Induced Human Trophoblast Cell Apoptosis and Miscarriage by Up-Regulating IP3R1/CaMKII/SGCB Pathway by Competitively Binding with miR-hz04

Huang

Dai

Mi³

et al. 2020

Preprint

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“…Alternatively, exposing rats to diesel exhaust (i.e., rich in PAH) can induce cardiac dysfunction and decrease VEGF levels subsequent to the activation of aromatic hydrocarbon receptors [52]. A significant decrease in VEGF levels was also reported in pregnant mice [53] and in the ischemic hindlimb of mice exposed to PAH Benzo(a)pyrene [54]. Conversely, after being exposed to Benzo(a)pyrene, induction of VEGF by PAH increased in epidermal [55] and lung cancer cells [56].…”

Section: Discussionmentioning

confidence: 99%

Serum VEGF Level Is Different in Adolescents Smoking Waterpipe versus Cigarettes: The Irbid TRY

et al. 2018

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Waterpipe (Wp) use is associated with most devastating diseases and particularly popular among adolescents. Vascular endothelium growth factor (VEGF) is essential for generating new vessels. The effect of smoking tobacco on VEGF is controversial and unknown among adolescents. Therefore, the current study compared serum VEGF in adolescents smoking cigarettes (Cg) only (9.3%), Wp only (19.6%), and dual (Wp and Cg) (36.4%) versus nonsmokers (34.6%) in adolescents. A self-reported questionnaire and enzyme-linked immunosorbent assay (ELISA) were used to obtain smoking status and serum VEGF, respectively, in 475 (age: 14.6 ± 1.0 years) boys (n = 263) and girls (n = 212) from Irbid, Jordan. The analysis showed that smoking status (R2 = 0.021; p = 0.001) and gender (R2 = 0.035; p = 0.000) can predict VEGF. Furthermore, 2-way-ANCOVA revealed that VEGF was lower in the dual cohort versus the Cg (33.4%; p = 0.04) and nonsmoker (29.6%; p = 0.003) cohorts; VEGF in smokers, was lower (33.6%; p = 0.04) in the Wp versus nonsmokers in the boys but not the girls. These results are unique and suggest that smoking lowers VEGF, which might adversely affect vascular growth and function. This is alarming given that adolescents are still in the development stage and smoking, particularly Wp, is popular among them. Therefore, interventions targeting smoking among schoolchildren are urgently needed to avoid the negative effects of smoking, especially on vascular health.

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“…Using the dose translation equation from animal to human [ 24 ], the human equivalent dose is 32-129.7 μ g/kg, which is in the range of the female PAH exposure levels illustrated in the human case study. Similar doses have been applied in other animal studies [ 10 ], which proved the doses can impair decidualization and decidual angiogenesis. And the effect of BaP and its metabolite BPDE on the function of trophoblast and miscarriage is not clear.…”

Section: Discussionmentioning

confidence: 57%

“…The human exposure to them is unavoidable. Previous studies in its reproductive toxicity have mainly focused on the ovarian disorders, endometrial cell apoptosis, and decidualization [ 10 , 20 , 21 ]. However, studies on the mechanism of adverse effect on first trimester trophoblasts are scarce.…”

Section: Discussionmentioning

confidence: 99%

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Environmental Pollutant Benzo[a]pyrene Induces Recurrent Pregnancy Loss through Promoting Apoptosis and Suppressing Migration of Extravillous Trophoblast

Yue

Jiang

Zhang

et al. 2020

BioMed Research International

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Objects. To investigate the effects of environmental pollutant benzo(a)pyrene (BaP) and its metabolite benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) on human trophoblasts and on murine miscarriages. Methods. The implantation sites, fetus resorption, and abnormal fetuses were studied in pregnant mice treated with different doses of BaP by oral gavage from day 1 to day 10 of gestation. Additionally, apoptosis and related signaling pathway, and the migration and invasion of trophoblasts, were assessed before and after exposure of BPDE in Swan 71 trophoblast cell. Besides, the migration and invasion, and its related signaling pathway, were assessed in villi obtained from women. Results. We observed a concentration-dependent incidence of abnormal murine fetuses, beginning with 0.1 mg/kg BaP; with a BaP concentration of 2 mg/kg, no fetuses developed. Correspondingly, a BPDE concentration-dependent apoptosis of human trophoblasts. Beginning with 0.5 μM BPDE exposure, Bax/Caspase-3 were increased and Bcl-2 decreased. Furthermore, BPDE also inhibited, in a dose-dependent manner, the migration of villous explants from elective abortion women, consistent with the reduced migration of villous explants from women with recurrent pregnancy loss (RPL), and reduced the cell immigration in Swan 71 trophoblasts, in a dose-dependent manner measured by transwell assays. Conclusions. Our study results provide mechanistic insight to the effect of BPDE on trophoblast dysfunction through enhanced cell apoptosis and inhibited migration, providing further experimental evidence to the causative links between BaP exposure and PRL.

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Exposure to benzo[a]pyrene impairs decidualization and decidual angiogenesis in mice during early pregnancy

Cited by 47 publications

References 50 publications

WITHDRAWN: Novel lncRNA-HZ04 Promotes BPDE-Induced Human Trophoblast Cell Apoptosis and Miscarriage by Up-Regulating IP3R1/CaMKII/SGCB Pathway by Competitively Binding with miR-hz04

WITHDRAWN: Novel lncRNA-HZ04 Promotes BPDE-Induced Human Trophoblast Cell Apoptosis and Miscarriage by Up-Regulating IP3R1/CaMKII/SGCB Pathway by Competitively Binding with miR-hz04

Serum VEGF Level Is Different in Adolescents Smoking Waterpipe versus Cigarettes: The Irbid TRY

Environmental Pollutant Benzo[a]pyrene Induces Recurrent Pregnancy Loss through Promoting Apoptosis and Suppressing Migration of Extravillous Trophoblast

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