Studies of early placental development in humans are difficult because of limitations on experimental material availability from the perimplantation period. We used a coculture system to determine the effects of various effector cell types on trophoblast differentiation. Enhanced green fluorescent protein (EGFP)-expressing H1 human embryonic stem cells were used in co-suspension with human term placental fibroblasts (TPFs) and dermal fibroblasts (CI2F) to form combination embryoid bodies (EBs), with the goal of recapitulating placental morphogenesis through incorporation of placental mesenchymal cells. Overall, the results demonstrated that when using mesenchymal cells for EB preparation from term placentas (TPF), combination EB-derived trophoblasts secrete higher levels of human chorionic gonadotropin (hCG) and progesterone compared to EBs made without effector cells, whereas there was no effect of dermal fibroblasts. This is due to the secretory activity of the EB-derived trophoblasts and not due to the number of differentiated trophoblasts per EB, demonstrating that nontrophoblast cells of the placenta can influence trophoblast endocrine activity.