A study on the placenta in stillbirth: an evaluation of molecular alterations through next generation sequencing

Placental dysfunction is one of the most common causes of Intrauterine Fetal Demise (IUFD). Due to its characteristics, the placenta may be the target of molecular research aimed to investigate potential causes of IUFD. In the literature, there are no studies on human placentas that have investigated possible associations between somatic mutations and the occurrence of IUFD. The aim of this study was to identify the presence of gene mutations in placental tissues in a series of cases of IUFD and to evaluate potential correlations with placental microscopic findings.

Thirty-seven samples of formalin-fixed and paraffin-embedded placental tissues were retrospectively selected from pregnancies ending in IUFD between 23rd to 40th week. Six control placentas of physiological pregnancies were included as controls. After sampling, made according to standardized protocol and conventional histopathological examination, placental tissues were subjected to DNA extraction and sequencing by means of Next Generation Sequencing with a 56-gene panel.

The most frequent mutation observed in 32/37 IUFD cases (86.5%) and absent in any of the 6 control placentas was in c-KIT gene, which is implicated in placental tissue differentiation. However, no significant correlation was found between the presence of individual gene mutations and placental histopatological findings.

As the present study found an elevated frequency of c-KIT mutation in IUFD, it further supports the hypothesis that c-KIT is involved in abnormal tissue differentiation leading to altered placental vascularization and function.