Dr Fergus McCarthy takes a look at the news this month…

Novielli et al examined mitochondrial DNA content and methylation in fetal cord blood of pregnancies with placental insufficiency. Pregnancies affected by intrauterine growth restriction and pre-eclampsia were examined for evidence of oxygen or nutrient restriction and oxidative stress by assessing mitochondria functionality and number.1 The content and methylation of mitochondrial DNA (mtDNA), in IUGR or pre-eclamptic singleton foetuses were examined for alterations in mtDNA levels and/or epigenetic control of mitochondrial loci relevant to replication (D-loop) and functionality (mt-TF/RNR1: protein synthesis, mt-CO1: respiratory chain complex).

Thirty-five term and 8 preterm controls, 31 IUGR, 17 PE/IUGR and 17 PE human singleton pregnancies with elective Caesarean delivery were analysed. Fetal cord blood was collected and evaluated for biochemical parameters. Extracted DNA was subjected to Real-time PCR to assess mtDNA content and analyzed for D-loop, mt-TF/RNR1 and mt-CO1 methylation by bisulfite conversion and pyrosequencing.

mtDNA levels were increased in all pathological groups compared to controls. Mitochondrial loci showed very low methylation levels in all samples; D-loop methylation was further decreased in the most severe cases. mt-CO1 methylation levels inversely correlated to mtDNA content.

Overall, the study demonstrated increased mtDNA levels in IUGR, PE/IUGR and PE cord blood which suggests a fetal response to placental insufficiency.

 

Hoeller et al investigated whether differences between early pre-eclampsia and early fetal growth restriction can be explained by differential placental expression patterns of sFlt-1, Flt-1, and PlGF.2 Placental tissues and maternal blood samples from six cases of pre-eclampsia, seven IUGR, and six age-matched controls were studied for mRNA and protein levels as well as protein localization and expression intensity. Neither placental PlGF mRNA and protein expression nor placental villous trophoblast expression intensity of PlGF was altered by placental dysfunction.

This line of work was continued when Ehrlich et al investigated whether differences between late-onset pre-eclampsia and intrauterine growth restriction can be explained by differential placental expression patterns of sFlt-1, Flt-1, and placental growth factor (PlGF).3

Similarly, placental tissues and maternal blood samples from seven patients with PE, five IUGR, and seven age-matched controls were studied for mRNA and protein levels as well as protein localization and expression intensity.

Placental PlGF mRNA and protein expression were not altered by placental dysfunction while placental villous trophoblast expression intensity of PlGF was increased. These studies concluded that high sFlt-1 concentrations may account for diminished maternal serum PlGF levels.

 

Finally this month, Li et al examined fatty acid-binding protein 4 (FABP4). FABP has been proposed to be a potential predictive marker of hypertensive disorders of pregnancy.4 Women with gestational diabetes mellitus (GDM) are more likely to develop hypertensive disorders of pregnancy. The aim of this study was to examine the relationship between plasma FABP4 in the second trimester of pregnancy and the risk of HDP in women with GDM.

A nested case-control study was performed within a large on-going prospective cohort study conducted at Peking University First Hospital. A total of 1344 women, who were diagnosed with GDM, participated. Of the 748 GDM women who agreed to the blood sample collection, 637 were followed until their delivery. The cases included GDM patients who developed gestational hypertension or pre-eclampsia (n = 41). The control group of GDM alone consisted of another 41 matched GDM women without major complications.

The incidence of GH/PE was 6.44% and 3.30% for pre-eclampsia. The level of the second-trimester plasma FABP4 in the GDM-GH/PE group was significantly higher than the GDM group (17.53±11.35 vs. 12.79±6.04 ng/ml, P = 0.020). The AUCROC for the second-trimester plasma FABP4 predicted GH/PE in the GDM patients alone was 0.647 (95%CI 0.529-0.766). Multivariate analysis showed that elevated second-trimester FABP4 level was independently associated with GH/PE in the GDM patients (OR 1.136 [95% CI 1.003-1.286], P = 0.045). Increased second-trimester plasma FABP4 independently predicted GH/PE in GDM patients.

 

References

  1. Novielli C, Mando C, Tabano S, et al. Mitochondrial DNA content and methylation in fetal cord blood of pregnancies with placental insufficiency. Placenta. 2017;55:63-70.
  2. Hoeller A, Ehrlich L, Golic M, et al. Placental expression of sFlt-1 and PlGF in early preeclampsia vs. early IUGR vs. age-matched healthy pregnancies. Hypertens Pregnancy. 2017;36(2):151-160.
  3. Ehrlich L, Hoeller A, Golic M, et al. Increased placental sFlt-1 but unchanged PlGF expression in late-onset preeclampsia. Hypertens Pregnancy. 2017;36(2):175-185.
  4. Li B, Yang H, Zhang W, et al. Fatty acid-binding protein 4 predicts gestational hypertension and preeclampsia in women with gestational diabetes mellitus. PloS one. 2018;13(2):e0192347.