275. Neuronal regeneration peptide (NRP): a novel trophoblast migration and survival enhancing factor
A. Singh A , J. Keelan A B and F. Sieg CA Liggins Institute, University of Auckland, Auckland, New Zealand
B Department of Pharmacology, University of Auckland, Auckland, New Zealand
C In vitro Sytems and Gene Discovery, Neuren Pharmaceuticals, Auckland, New Zealand
Reproduction, Fertility and Development 17(9) 113-113 https://doi.org/10.1071/SRB05Abs275
Submitted: 26 July 2005 Accepted: 26 July 2005 Published: 5 September 2005
Abstract
Autocrine and paracrine factors regulate survival, proliferation, migration and invasion of placental cytotrophoblasts cells. While trophoblast migration appears to be tightly controlled, the nature of the chemoattractive factors that facilitate and direct trophoblast invasion remains undefined. Our group recently discovered a chemottractive factor (NRP) that exerts its biological activities on the CNS. Studies of NRP actions reveal extensive influences on postnatal neuronal migration, differentiation and survival. Based on the neuronal activities of NRPs and parallels between neuronal and placental cell behavior patterns, we speculated that NRPs could be involved in placental development.
Migration assays were performed over 22 h using Boyden chambers pre-coated with NRP and laminin (n = 6 chambers per condition), to test the effect of NRPs on trophoblast migration. CTBs were isolated from term placentas by trypsin digestion and Percoll purification, and experiments were conducted within 6 h. Trophoblasts were seeded into the inner chamber (50 000 cells/well) in M199 media supplemented with 10% FBS and antibiotics. Total number of cells migrating was counted. Migration was increased by 95 ± 14 % (mean ± SEM) in the presence of 100 fM NRP (P = 0.0016, t-test) compared to controls (bovine serum albumin). Survival assays were also performed using both primary trophoblasts and Jar choriocarcinoma cells. Apoptosis over 48 h, induced by treatment with TNF-α (5 ng/mL) and IFN-γ (100 U/mL), was completely abrogated by 10 pM NRP in Jar cells and 1 pM in primary trophoblasts, as judged by MTT assay (mitochondrial activity).
Inadequate placentation is implicated in the pathogenesis of a number of serious pregnancy disorders such as preeclampsia. Our findings suggest important roles for NRPs in regulating trophoblast migration and survival. The possibility that defective NRP actions may be involved in various placental pathologies, or that NRPs could be used pharmacologically to augment placentation, remain to be explored.
