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Epigenetic changes in preterm birth placenta suggest a role for ADAMTS genes in spontaneous preterm birth.
- Source :
-
Human molecular genetics [Hum Mol Genet] 2019 Jan 01; Vol. 28 (1), pp. 84-95. - Publication Year :
- 2019
-
Abstract
- Preterm birth (PTB) affects approximately 1 in 10 pregnancies and contributes to approximately 50% of neonatal mortality. However, despite decades of research, little is understood about the etiology of PTB, likely due to the multifactorial nature of the disease. In this study, we examined preterm and term placentas, from unassisted conceptions and those conceived using in vitro fertilization (IVF). IVF increases the risk of PTB and causes epigenetic change in the placenta and fetus; therefore, we utilized these patients as a unique population with a potential common etiology. We investigated genome-wide DNA methylation in placentas from term IVF, preterm IVF, term control (unassisted conception) and preterm control pregnancies and discovered epigenetic dysregulation of multiple genes involved in cell migration, including members of the ADAMTS family, ADAMTS12 and ADAMTS16. These genes function in extracellular matrix regulation and tumor cell invasion, processes replicated by invasive trophoblasts (extravillous trophoblasts (EVTs)) during early placentation. Though expression was similar between term and preterm placentas, we found that both genes demonstrate high expression in first- and second-trimester placenta, specifically in EVTs and syncytiotrophoblasts. When we knocked down ADAMTS12 or ADAMTS16in vitro, there was poor EVT invasion and reduced matrix metalloproteinase activity, reinforcing their critical role in placentation. In conclusion, utilizing a population at high risk for PTB, we have identified a role for ADAMTS gene methylation in regulating early placentation and susceptibility to PTB.
- Subjects :
- ADAMTS Proteins physiology
Cell Movement
DNA Methylation genetics
Epigenesis, Genetic genetics
Epigenomics methods
Extracellular Matrix physiology
Female
Fertilization in Vitro adverse effects
Humans
Placenta metabolism
Pregnancy
Premature Birth etiology
Transcriptome
Trophoblasts physiology
ADAMTS Proteins genetics
Placentation genetics
Premature Birth genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2083
- Volume :
- 28
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Human molecular genetics
- Publication Type :
- Academic Journal
- Accession number :
- 30239759
- Full Text :
- https://doi.org/10.1093/hmg/ddy325