Aims: 

Pituitary adenylate cyclase-activating polypeptide (PACAP) can be found in endocrine organs and plays a role in reproductive functions, including pregnancy. Also, it has survival-promoting effects. In the present study we measured PACAP38 and 27 concentrations in first trimester and full-term human placentas. The effects of PACAP1-38 and its antagonist, PACAP6-38 were investigated on the survival of human choriocarcinoma cell line, JAR and extravillous cytotrophoblastic cell line, HIPEC65. Proliferation and invasion were also studied on HIPEC65 cells.

Methods: 

PACAP-like IR was measured using radioimmunoassay (RIA). Trophoblastic cell survival was investigated using flow cytometry and MTT- or WST-1 assay in cells exposed to methotrexate. Proliferation and invasion assays were performed.

Results: 

We found high concentrations of PACAP38 and lower levels of PACAP27 in different parts of the full-term human placenta. PACAP38 content in the placenta increased significantly during pregnancy from first to third trimester, both in the maternal and the fetal side. PACAP27 levels, however, only showed significant increase in the maternal side. It was found that neither PACAP1-38 nor PACAP6-38 influenced cell survival alone in either cell lines. MTX treatment caused significant cell death both in JAR and HIPEC65 cell cultures. PACAP1-38 and PACAP6-38 treatment could not alter the cell death inducing effect of MTX. PACAP1-38 decreased invasion, while increased proliferation of HIPEC65 cells, but the antagonist had no effect.

Conclusion: 

These findings are in contradiction with the general cytoprotective and antiapoptotic effects of PACAP found in different other cell lines. The present observations further support the significance of this neuropeptide in the human placenta, and its diverse effects in different cells/tissues.

Support: 

OTKA K72592, F67830, CNK 78480, ETT 278-04/2009, Bolyai Fellowship