Genetics, not the uterine environment, drive the formation of trophoblast inclusions: Insights from a twin study

Abstract

IntroductionTrophoblast inclusions (TIs) are associated with aneuploidy and pregnancy loss and have thus been considered to be a marker of genetic abnormality. However, to date, no study has specifically explored whether TIs are a manifestation of fetal genetics or, rather, the result of the intrauterine environment. The goal of this study was to compare the frequency of TIs in the placentas of monozygotic (MZ) and dizygotic (DZ) twin pairs in order to determine whether the formation of TIs is genetically driven or not. MethodsWe performed a retrospective case series of placentas from 48 twin pairs. The placentas were grouped based on zygosity: MZ, DZ, or unknown (UZ). The average number of total TIs per slide was calculated for each twin individual and the mean absolute difference in the total TIs per slide between the twin pairs was calculated for each zygosity group and compared. ResultsThe mean difference in the total TIs per slide for DZ twins was significantly greater than the mean difference in the total TIs per slide for MZ twins (p = 0.003). The mean difference in the total TIs per slide for the UZ group was also significantly greater than the mean difference in total TIs per slide between MZ twin pairs (p = 0.028). DiscussionOur finding that MZ twins were significantly more concordant than DZ twins for the average number of TIs per slide supports the conclusion that TIs are intrinsic to the genetics of the fetus, not the uterine environment.