Association between proNGF receptors and apoptotic factors in human placentae

Earlier studies have shown higher apoptosis in the pre-term placenta as compared to term. However, the exact mechanisms triggering these are not completely understood. Studies in neuronal and non-neuronal tissues have shown that the precursor form of NGF (proNGF) triggers apoptosis through preferential activation of p75NTR and sortilin receptors. We therefore, investigated placental expression of proNGF, mature NGF, p75NTR, co-receptor sortilin and their association with apoptosis. We further compared the levels of pro-protein convertase, furin between samples having high and low proNGF: mature NGF ratio.

Placenta samples were collected from women delivering at term (≥37 weeks; n = 41) and preterm (<37 weeks; n = 44). The protein levels of NGF, proNGF, p75NTR, Bax, Bcl-2 and furin were estimated by ELISA. Mean values of variables between different groups were compared using the independent sample t-test and associations were studied by Pearson correlation analysis.

The placental mature NGF, proNGF and p75NTR protein levels were comparable between groups. Bax: Bcl-2 ratio was higher in preterm (p < 0.05) compared to term placenta. p75NTR was positively associated with Bax levels and sortilin levels were positively associated with p75NTR in whole cohort as well as individual groups.

The higher Bax: Bcl-2 ratio in preterm placenta suggests the sensitivity to apoptosis. There were no differences in levels of NGF, proNGF, p75NTR, sortilin, and furin between groups. The observed associations between p75NTR, sortilin and Bax suggest that p75NTR and sortilin mediated signalling may be involved in the mechanisms leading to higher apoptosis in preterm placentae.