Paternal lipopolysaccharide exposure induced intrauterine growth restriction via the inactivation of placental MEST/PI3K/AKT pathway in mice

被引:2
作者
Jiang, Pei-Ying [1 ]
Lin, Shuai [1 ]
Liu, Jie-Ru [1 ]
Liu, Yan [1 ]
Zheng, Li-Ming [1 ]
Hong, Qiang [1 ]
Fan, Yi-Jun [2 ]
Xu, De-Xiang [3 ,4 ]
Chen, Yuan-Hua [1 ,3 ]
机构
[1] Anhui Med Univ, Sch Basic Med Sci, Hefei 230032, Peoples R China
[2] Anhui Med Univ, Affiliated Hosp 2, Dept Obstet & Gynecol, Hefei 230601, Peoples R China
[3] Anhui Med Univ, Key Lab Environm Toxicol Anhui Higher Educ Inst, Hefei 230032, Peoples R China
[4] Anhui Med Univ, Dept Toxicol, Hefei 230032, Peoples R China
基金
中国国家自然科学基金;
关键词
Paternal lipopolysaccharide; Intrauterine growth restriction; Mesoderm specific transcript; PI3K; AKT pathway; Cell proliferation; Mice; FETAL-DEATH; PROTECTS;
D O I
10.1007/s00204-023-03584-3
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Maternal lipopolysaccharide (LPS) exposure during pregnancy has been related to IUGR. Here, we explored whether paternal LPS exposure before mating impaired fetal development. All male mice except controls were intraperitoneally injected with LPS every other day for a total of five injections. The next day after the last LPS, male mice were mated with untreated female mice. Interestingly, fetal weight and crown-rump length were reduced, while the incidence of IUGR was increased in paternal LPS exposure group. Additionally, paternal LPS exposure leaded to poor placental development through causing cell proliferation inhibition and apoptosis. Additional experiment demonstrated that the inactivation of placental PI3K/AKT pathway might be involved in paternal LPS-induced cell proliferation inhibition and apoptosis of trophoblast cells. Furthermore, the mRNA and protein levels of mesoderm specific transcript (MEST), a maternally imprinted gene with paternal expression, were significantly decreased in mouse placentas from paternal LPS exposure. Further analysis showed that paternal LPS exposure caused the inactivation of placental PI3K/AKT pathway and then cell proliferation inhibition and apoptosis might be via down-regulating placental MEST. Overall, our results provide evidence that paternal LPS exposure causes poor placental development and subsequently IUGR may be via down-regulating MEST/PI3K/AKT pathway, and then inducing cell proliferation inhibition and apoptosis in placentas.
引用
收藏
页码:2929 / 2941
页数:13
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