Abstract

Neurotrophic factors are a group of proteins that act as paracrine and autocrine growth factors. They are involved in the regulation of morphogenesis and development of several tissues. The present study aims to evaluate, for the first time, the expression of Neurotrophin-3 in the human placenta during normal pregnancy and in preeclampsia and chorioamnionitis. Neurotrophin-3 mRNA, assessed by RT-PCR analysis in six term placentas, were observed in all the specimens examined. Neurotrophin-3 protein expression and tissue distribution was evaluated by immunohistochemistry in placenta samples from uncomplicated first trimester (n = 5) and term (n = 5) pregnancies as well as in specimens from preeclampsia (n = 5) and chorioamnionitis (n = 5). In first trimester specimens, strong immunoreactivity was present in villous stromal cells, in the cyto- and syncytiotrophoblast, in decidua cells and in endometrial glands. Third trimester specimens showed prominent immunostaining in cyto- and syncytiotrophoblast cells, in decidua cells and in the amniotic membranes. Villous stromal cells were weakly stained. Similar protein localization was observed in placentas with preeclampsia and chorioamnionitis. In the latter, however, positive villous stromal cells increased in number and in staining intensity when compared with controls and preeclampsia (p < 0.001). The roles of Neurotrophin-3 in pregnancy are presently unknown. A regulatory function on placenta and foetal brain development and maternal inflammatory response may be hypothesized.

Highlights

  • Neurotrophins (NT) are a group of functionally and structurally related polypeptides that share about 50% amino acid sequence and act as paracrine and autocrine growth factors

  • Neurotrophic factors comprise a family of proteins including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3) and neurotrophin 4 (NT-4)

  • We have previously demonstrated the expression of NGF mRNA and peptide in human trophoblast, decidua and fetal membranes in first and third trimester of pregnancy, hypothesizing a role for this neurotrophic factor in the regulation of placental development and in fetal growth.[14]

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Summary

Introduction

Neurotrophins (NT) are a group of functionally and structurally related polypeptides that share about 50% amino acid sequence and act as paracrine and autocrine growth factors. One gene family encodes the neurotrophins, and amino acids are clustered in conserved regions alternated by variable regions; this combination defines the biological functions of these proteins.[1] Neurotrophic factors comprise a family of proteins including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3) and neurotrophin 4 (NT-4) These proteins control generation, survival, differentiation and death of neurons in the peripheral and central nervous system in embryonic and postnatal stages, as well as neuronal maintenance later in life.[2,3] Outside the nervous system, NTs can regulate morphogenesis, proliferation and apoptosis[4,5,6] and seem to be involved in the development of organs such as kidney, muscles and heart.[7,8]. In migratory neural crest cells, the reported mitotic effect of NT-3 indicates an involvement in gangliogenesis and highlights an autocrine and/or paracrine action required for proliferation, differentiation and survival of sympathetic neuroblasts.[13]

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