Table 1 DNA hydroxymethylation studies in placentas associated with pregnancy complications, such as intrauterine growth restriction, preeclampsia, and pregnancy loss.
From: The role of DNA hydroxymethylation and TET enzymes in placental development and pregnancy outcome
Pathology | Species | Gestational age | Sampling location | Number of samples | Methodology | Findings | Ref |
|---|---|---|---|---|---|---|---|
IUGR | Rat | – | – | IUGR: n = 12 non-IUGR: n = 12 | Gluc-MS-qPCR; RT-qPCR | In IUGR rat, induced by gestational protein deficiency, the levels of 5hmC in the Wnt2 promoter and the Wnt2 expression were decreased | 54 |
Human | sIUGR twins: 31–35 weeks | Placental villous tissues around umbilical cord insertion region | 19 pairs of sIUGR twins | UPLC-MS/MS | Decrease in global DNA hydroxymethylation in sIUGR placentas | 48 | |
Rat | 16 days | – | Rats exposed to TCE: n = 8 Controls: n = 7 | 5-hmC DNA ELISA; RT-qPCR | Fetal weight is negatively influenced by exposure to maternal TCE. Placentas of rats exposed to TCE have increased 5hmC global levels and increased expression of Tet3 | 55 | |
Human | sIUGR twins: 32.58 ± 2.19 weeks Normal MC twins: 36.02 ± 1.17 weeks | Placental villous tissues around umbilical cord insertion region | 13 pairs of sIUGR twins 18 pairs of normal MC twins | hMeDIP-qPCR; Dot blot; IHC | Decreased global levels of 5hmC in sIUGR placentas Decreased ANGPTL4 expression and ANGPTL4 promoter with aberrant levels of 5hmC under hypoxic conditions | 49 | |
Human | IUGR: 37.12 ± 1.10 weeks non-IUGR: 38.54 ± 1.26 weeks | Placental villous tissues around umbilical cord insertion region | IUGR: n = 21 non-IUGR: n = 9 | 5-hmC DNA ELISA; RT-qPCR | No differences in global DNA hydromethylation were detected between IUGR and non-IUGR samples IUGR placentas showed increased TET3 expression | 53 | |
Preeclampsia | Human | PE: 36 ± 0,5 weeks non-PE: 37.3 ± 0.4 weeks | Placental tissue from the center of the maternal side | PE: n = 21 non-PE: n = 16 | Western blot; Dot blot; IHC | PE placentas showed that 5hmC global levels and TETs expression were decreased | 60 |
Human | PE: 38.25 ± 0.85 weeks non-PE: 38.62 ± 0.63 weeks | – | PE: n = 20 non-PE: n = 20 | hMeDIP-seq; (h)MeDIP-qPCR | Severe PE and non-PE samples showed genome-wide mapping of 5hmC differences however, no differences in global DNA hydroxymethylation were observed | 63 | |
Human | PE: 35.16(30.29–39) weeks non-PE: 39.49(38.86–40.86) weeks | Placental tissue from the maternal side, around the central villus area | PE: n = 13 non-PE: n = 11 | RT-qPCR; Western blot; Dot blot; IHC | 5hmC levels and TET2 mRNA and protein expression are decreased in PE placentas | 61 | |
Human | PE: 37.27 ± 0.36 non-PE: 38.89 ± 0.13 weeks | Placental tissue from the center of the maternal side | PE: n = 10 non-PE: n = 10 | RT-qPCR; IHC; Western blot.; IHC; ELISA | Global 5hmC and TET expression are decreased in PE placentas and hypoxic trophoblast | 62 | |
Human | PE: 39.33 ± 1.37 non-PE: 40.65 ± 0.45 weeks | – | PE: n = 10 non-PE: n = 9 | IHC | No differences in 5hmC levels between PE placentas and non-PE. However, the levels of 5hmC are different across gestation and between different placental cell types | 29 | |
Pregnancy loss | Human | 6–8 weeks | Chorionic villi | Early PL: n = 100 (6 weeks, n = 27; 7 weeks, n = 35; 8 weeks, n = 38) and normal pregnancy: n = 126 (6 weeks, n = 36; 7 weeks, n = 40; 8 weeks, n = 50) | RT-qPCR; Dot-blot; Western Blot; IHC | Expression of TETs and 5hmC in normal villus decreased with increasing gestational age. TET1-3 expression was lower in the early PL group than normal pregnancy group | 71 |
Human | 12–24 weeks | Chorionic villi | Placenta controls: n = 16 Idiopathic PL: n = 19 | RT-qPCR; ELISA assay | Upregulation of TET2 and TET3 in placental samples from idiopathic PL; No significant difference in global 5hmC levels was observed | 72 |