Mitochondrial dysfunction-induced high hCG associated with development of fetal growth restriction and pre-eclampsia with fetal growth restriction

被引:13
|
作者
Kiyokoba, Ryo [1 ,2 ]
Uchiumi, Takeshi [1 ,3 ]
Yagi, Mikako [1 ,3 ]
Toshima, Takahiro [1 ]
Tsukahara, Shigehiro [1 ]
Fujita, Yasuyuki [2 ]
Kato, Kiyoko [2 ]
Kang, Dongchon [1 ]
机构
[1] Kyushu Univ, Grad Sch Med Sci, Dept Clin Chem & Lab Med, Higashi Ku, Maidashi 3-1-1, Fukuoka 8128582, Japan
[2] Kyushu Univ, Grad Sch Med Sci, Dept Obstet & Gynecol, Higashi Ku, Maidashi 3-1-1, Fukuoka 8128582, Japan
[3] Kyushu Univ, Grad Sch Med Sci, Dept Hlth Sci, Higashi Ku, Maidashi 3-1-1, Fukuoka 8128582, Japan
来源
SCIENTIFIC REPORTS | 2022年 / 12卷 / 01期
关键词
HUMAN CHORIONIC-GONADOTROPIN; HUMAN PLACENTA; TROPHOBLAST; HYPOXIA; PREGNANCY; EXPRESSION; HYPERTENSION; METABOLISM; REGULATOR; RECEPTOR;
D O I
10.1038/s41598-022-07893-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Fetal growth restriction (FGR) and pre-eclampsia with fetal growth restriction (PE/FGR) are high-risk perinatal diseases that may involve high levels of human chorionic gonadotropin (hCG) and mitochondrial dysfunction. However, little is known about how these factors affect placental function. We investigated how mitochondrial dysfunction and high hCG expression affected placental function in unexplained FGR and PE/FGR. We observed elevated expression of hCG beta and growth differentiation factor 15 mRNA and protein levels in the placenta with both diseases. Likewise, antiangiogenic factors, such as Ang2, IP10, sFlt1, IL8, IL1B, and TNF alpha, were also upregulated at the mRNA level. In addition, the expression of COXI and COXII which encoded by mitochondrial DNA were significantly decreased in both diseases, suggesting that mitochondrial translation was impaired. Treatment with hCG increased Ang2, IP10, IL8, and TNF alpha mRNA levels in a dose-dependent manner via the p38 and JNK pathways. Mitochondrial translation inhibitors increased hCG beta expression through stabilization of HIF1 alpha, and increased IL8 and TNF alpha mRNA expression. These results revealed that high expression of hCG due to mitochondrial translational dysfunction plays an important role in the pathogenesis of FGR and PE/FGR.
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页数:15
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