Possible Role of Paternal Aberrant Imprinting in Placental Development: A Study in Tamoxifen Treatment Rat Model

Genomic imprinting is known to regulate fetal growth and development. Studies from our laboratory have demonstrated that treatment of adult male rats with tamoxifen increased post-implantation loss around mid-gestation. Microarray analysis of resorbing vs. normal embryos revealed aberrant expression of imprinted genes and deregulation of genes associated in placental function. In the present study, expression levels of placental lineage specific genes and imprinted genes implicated in placental development in resorbing embryos sired by tamoxifen treated male rats were evaluated by qPCR. The morphology of these embryos sired was assessed by routine haematoxylin-eosin staining. Flow cytometry was done to confirm the observed results on increase in trophoblast giant cells. Expression of genes responsible for the formation of trophoblast giant cells, spongiotrophoblast and labyrinth was affected in the resorbing embryos. Morphology of the normal and resorbing embryos sired by tamoxifen treated male rats showed increase in giant trophoblast cells along with reduction in spongiotrophoblast and labyrinth trophoblast in the resorbing embryos. The study suggests that aberrant imprinting observed upon tamoxifen treatment of adult male rats affects placental development by altering the bias towards development of one cell lineage, thus abrogating normal placental structures and highlights role for paternal imprinting in placentation.