Placental OLAH Levels Are Altered in Fetal Growth Restriction, Preeclampsia and Models of Placental Dysfunction

被引:6
作者
de Alwis, Natasha [1 ,2 ,3 ,4 ]
Beard, Sally [1 ,2 ,3 ,4 ]
Binder, Natalie K. [1 ,2 ,4 ]
Pritchard, Natasha [2 ,4 ,5 ]
Kaitu'u-Lino, Tu'uhevaha J. [2 ,4 ,5 ]
Walker, Susan P. [2 ,4 ]
Stock, Owen [4 ]
Groom, Katie [6 ]
Petersen, Scott [7 ]
Henry, Amanda [8 ]
Said, Joanne M. [4 ,9 ]
Seeho, Sean [10 ]
Kane, Stefan C. [4 ,11 ]
Tong, Stephen [2 ,4 ,5 ]
Hui, Lisa [2 ,3 ,4 ]
Hannan, Natalie J. [1 ,2 ,3 ,4 ]
机构
[1] Mercy Hosp Women, Therapeut Discovery & Vasc Funct Pregnancy Grp, Heidelberg, Vic 3084, Australia
[2] Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3084, Australia
[3] Northern Hlth, Epping, Vic 3076, Australia
[4] Univ Melbourne, Dept Obstet & Gynaecol, Parkville, Vic 3010, Australia
[5] Mercy Hosp Women, Translat Obstet Grp, Heidelberg, Vic 3084, Australia
[6] Univ Auckland, Liggins Inst, Auckland 1023, New Zealand
[7] Mater MothersHosp, Ctr Maternal Fetal Med, South Brisbane, Qld 4101, Australia
[8] Univ New South Wales, Sch Clin Med, UNSW Med & Hlth, Discipline Womens Hlth, Sydney, NSW 2052, Australia
[9] Joan Kirner Womens & Childrens Sunshine Hosp, Maternal Fetal Med, St Albans, Vic 3021, Australia
[10] Univ Sydney, Fac Med & Hlth, Sydney Med Sch Northern, Women & Babies Res, St Leonards, NSW 2065, Australia
[11] Royal Womens Hosp, Dept Maternal Fetal Med, Parkville, Vic 3052, Australia
基金
英国医学研究理事会;
关键词
placenta; OLAH; fetal growth restriction; preeclampsia; fatty acid synthesis; pregnancy; FATTY-ACIDS; GESTATIONAL-AGE; MATERNAL BLOOD; EXPRESSION; HYPERTENSION; PREGNANCY; SFLT-1; CELLS;
D O I
10.3390/antiox11091677
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Previously, we identified elevated transcripts for the gene Oleoyl-ACP Hydrolase (OLAH) in the maternal circulation of pregnancies complicated by preterm fetal growth restriction. As placental dysfunction is central to the pathogenesis of both fetal growth restriction and preeclampsia, we aimed to investigate OLAH levels and function in the human placenta. We assessed OLAH mRNA expression (qPCR) throughout pregnancy, finding placental expression increased as gestation progressed. OLAH mRNA and protein levels (Western blot) were elevated in placental tissue from cases of preterm preeclampsia, while OLAH protein levels in placenta from growth-restricted pregnancies were comparatively reduced in the preeclamptic cohort. OLAH expression was also elevated in placental explant tissue, but not isolated primary cytotrophoblast cultured under hypoxic conditions (as models of placental dysfunction). Further, we discovered that silencing cytotrophoblast OLAH reduced the expression of pro- and anti-apoptosis genes, BAX and BCL2, placental growth gene, IGF2, and oxidative stress gene, NOX4. Collectively, these findings suggest OLAH could play a role in placental dysfunction and may be a therapeutic target for mitigating diseases associated with this vital organ. Further research is required to establish the role of OLAH in the placenta, and whether these changes may be a maternal adaptation or consequence of disease.
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页数:15
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