Deregulation of PLAGL1 as a risk factor for preterm labor and preterm birth
Preterm birth is the most common cause of death among infants worldwide. Placental dysfunction is a
frequent cause of Preterm birth. Our research group has associated impaired cognitive development in
early childhood with preterm labor, as no differences were detected between preterm birth and term born
after suspected preterm labor (C Paules et al., 2017). Subsequently, we have identified placental changes in
both gene expression (D Oros et al., 2017) and gene-specific methylation patterns associated with preterm
labor (J Schoorlemmer et al., manuscript submitted and positively reviewed). PLAGL1 is an imprinted gene
that encodes a nuclear transcription factor with cell growth suppressing function. We now provide evidence
that altered methylation and expression of the PLAGL1 gene in placenta is associated with preterm labor. As
this association is based on a relatively small sample size, we propose to analyze a much larger study cohort
and further prove deregulation of PLAGL1 in preterm birth and preterm labor. We will compare genetic
variation, as well as levels of mRNA expression and DNA methylation in a large cohort of placental biopsies
from preterm, term born after suspected preterm labor and uneventful pregnancies. Analysis will extend
towards other imprinted genes potentially regulated by PLAGL1. To study PLAGL1 function in human
placenta, we will also overexpress PLAGL1 in stem cell-derived trophoblast cells and use transcriptomics to
survey alterations in gene expression, which in turn may be related to preterm labor.
Preterm birth is the most common cause of death among infants worldwide. Placental dysfunction is a
frequent cause of Preterm birth. Our research group has associated impaired cognitive development in
early childhood with preterm labor, as no differences were detected between preterm birth and term born
after suspected preterm labor (C Paules et al., 2017). Subsequently, we have identified placental changes in
both gene expression (D Oros et al., 2017) and gene-specific methylation patterns associated with preterm
labor (J Schoorlemmer et al., manuscript submitted and positively reviewed). PLAGL1 is an imprinted gene
that encodes a nuclear transcription factor with cell growth suppressing function. We now provide evidence
that altered methylation and expression of the PLAGL1 gene in placenta is associated with preterm labor. As
this association is based on a relatively small sample size, we propose to analyze a much larger study cohort
and further prove deregulation of PLAGL1 in preterm birth and preterm labor. We will compare genetic
variation, as well as levels of mRNA expression and DNA methylation in a large cohort of placental biopsies
from preterm, term born after suspected preterm labor and uneventful pregnancies. Analysis will extend
towards other imprinted genes potentially regulated by PLAGL1. To study PLAGL1 function in human
placenta, we will also overexpress PLAGL1 in stem cell-derived trophoblast cells and use transcriptomics to
survey alterations in gene expression, which in turn may be related to preterm labor.