Effect of ablation of trophoblast-derived signals on gene expression in the decidua of early pregnancy
Maternal-embryonic interactions play a critical role in successful pregnancy, with particular emphasis on the decidual-trophoblast interaction, which have been long recognized to exert a paracrine influence through the trophoblast cells on the progression of decidualization and the function of decidual cells. Despite this knowledge, the full extent of the embryo's impact on the decidua remains largely unexplored. To investigate the influence of embryonic signals on the maternal decidua, we utilized Prl3d1Cre/Cre mice mated with R26DTA/DTA mice, resulting in the generation of Prl3d1Cre/+, R26DTA/+ conceptus. In these conceptuses, the primary trophoblast giant cells (pTGCs) were selectively ablated by diphtheria toxin A (DTA). The pTGCs are the key embryonic cells that directly interact with the maternal decidua. Following the ablation of pTGCs, we observed impaired decidualization, as indicated by altered expression of genes related to decidualization or decidual function, such as Prl8a2, Wnt4, Bmp2, Alpl, and Hsd11b2, as well as a reduction in the interferon response in the decidua on day 6.5 of early pregnancy. Additionally, we found significant downregulation of numerous lipid-related biological effects in both deciduae on day 6.5 and day 8 of early pregnancy. These findings shed light on the complex interactions between the maternal and embryonic components during early pregnancy and underscore the importance of embryonic-derived influences on decidual lipid metabolism. Overall design: we employed a mouse model with selective ablation of pTGCs using the pTGC-specific Prl3d1-Cre driven Rosa26-DTA expression system. RNA sequencing was performed on two biological replicates of WT and DTA deciduae, after removing myometrium and embryo tissues from the whole uteri