The novel role of 3',5'-guanosine monophosphate (cGMP) on the differentiation of trophoblasts: comparison with the effects of 3',5'-adenosine monophosphate (cAMP).

We investigated the effects of 3',5'-guanosine monophosphate (cGMP) on the differentiation of human trophoblasts. Isolated cytotrophoblasts were cultured with 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) or 8-bromoadenosine 3'5-cyclic monophosphate (8-Br-cAMP) and then stained immunocytochemically with anti-human chorionic gonadotropin (anti-hCG) antibody to identify hCG expression as an index of differentiation. Concurrently, morphological changes from cytotrophoblasts to syncytiotrophoblasts were analyzed. Both 8-Br-cGMP and 8-Br-cAMP enhanced the expression of hCG in cultured cytotrophoblasts with the differentiation of cytotrophoblasts to syncytiotrophoblasts dose-dependently. With regard to trophoblast proliferation, 8-Br-cAMP but not 8-Br-cGMP enhanced [3H]thymidine uptake by these cells. hCG, a trophoblast-specific glycoprotein hormone has been identified as a potent growth factor for trophoblasts, also increased [3H]thymidine uptake and the intracellular 3',5'-adenosine monophosphate (cAMP) concentration. However, in this study, hCG did not increase the concentration of intracellular cGMP. We also showed that sodium nitroprusside (SNP), which is a donor of nitric oxide (NO), enhanced intracellular cGMP concentration. These results suggest that cGMP enhances trophoblast differentiation without affecting their proliferation, while cAMP enhances both differentiation and proliferation. We conclude that an alternative pathway mediated through cGMP is responsible for the differentiation of trophoblasts. NO may be involved in trophoblast differentiation with an increase in cellular cGMP level.