4 Discussion
PE is a serious pregnancy complication that endangers the safety of mother and fetus and the quality of life. Though the exact pathogenesis of PE is still not clear, different pathogenesis finally showed a same pathological manifestations: poor placental perfusion and deficient trophoblast cells invasion, which eventually may result in placental dysfunction in the development of PE. Early blockage of trophoblasts may protect the embryo from high concentrations of oxygen. However, when the trophoblast cells are insufficiently infiltrated, the placenta will prematurely loss its blockage effect causing the occurrence of PE16. In recent years, genetics have also been considered as one of the causes of PE17.
Neurotrophins are considered to be new pre-angiogenic factors that can affect endothelial cells and work through myeloid progenitor cells18. BDNF, as the one of member of Neurotrophins family, participates in neovascularization and contributes to the development of placenta through activating the expression of TrkB receptors19. The activated TrkB receptors conferred an antiapoptotic effect in the process of oxidative stress, contributing to resist adverse conditions5. Animal experiments20also showed that the BDNF / TrkB signaling system is implicated in embryo implantation, placental development and fetal growth. Before embryo implantation , BDNF can facilitate the growth of blastocyst and resist the apoptosis of embryonic cell during embryonic development19. Many studies proved there is a difference in the level of BDNF between PE and healthy pregnant women, suggesting that BDNF emits its effect in the occurrence and development of PE 5, 8, 21-23. As a functional SNP in BDNF , Val66Met first described by Egan et al.24 in 2003 and quickly regarded as a commonBDNF mutation that can affect the functional expression of BDNF and suppress the transport and release of BDNF-containing vesicles in synapses25. In addition, MF et al. found cells transfected with Met alleles of BDNF can alter the activity-dependent secretion of BDNF14. This polymorphism has since been thought to be associated with many diseases, such as schizophrenia14, neurodegenerative disease26and so on.
In this study, we first screened the matching samples from PE patients and analyzed the alleles of BDNF Val66Met locus in PE patients based on large sample research objects. Although there was no significant difference in genotypic distribution of BDNF Val66Met polymorphism in the PE group compared with the healthy control group, we found that the allele was significantly statistical difference. The ratio of allele G to A in PE group as a protective factor in the onset, suggesting that allele A may increase the risk of PE. This is the first description that BDNF Val66Met locus is associated with occurrence of PE. Besides, we detected the level of BDNF in the placenta tissue, and found a lower expression of BDNF in the placenta of PE patients, further confirming the role of BDNF placental development and indicating the depression of BDNF may be related to the occurrence of PE. Vandita et al. 8indicated maternal BDNF levels, cord BDNF levels and BDNF mRNA level are lower in PE group than control group in 61 PE pregnant women and 89 healthy women. They also found the marternal BDNF in case group have a statistical reduce in the another study10 of 106 PE pregnant women and 95 healthy women. Kamini et.al27also have proved this result in a study that there are 72 PE women and 102 healthy pregnant women. These studies are consistent with our results. However, some reports have shown that the BDNF level are higher in PE group than the control group. J. Bienertova-Vasku et.al 23 measured BDNF levels of cord blood in 12 cases PE patients and 34 healthy controls, and suggested BDNF have an obvious increase in PE group. The BDNF levels in maternal plasma have also been observed to be elevated in 15 PE women in case group 5, inferred that small sample size may be the reason for the results that BDNF levels showed an increasing trend in case group. Therefore, these controversial results drive us to further investigate the role of BDNF in PE and explore probable reason for the low BDNF expression of PE placentas.
Then, we conducted a mother-fetal pairing study to further explore the mother-to-fetal transmission of BDNF Val66Met and anticipate to find out whether this variants is associated with the poor neonatal prognosis related to PE. As we all known, PE not only threatens the life and health of pregnant women, but also it has a severe adverse prognosis for newborns. By large sample clinical data analysis, we found pregnant women with PE have lower gestational age and birth weight of fetus. The higher incidence of premature birth and lower birth weight will necessarily affect newborn quality of life and survival. BDNF can act on embryos TrkB in preimplantation, promoting early embryo development and inhibiting embryo apoptosis in a paracrine / autocrine manner28. BDNF can play an important role in placental development and fetal growth through the TrkB signaling system and penetrate the uterus-placenta barrier in animal models7, 29. Here, we analyzed the BDNF Val66Met polymorphism of the newborn, and performed mother-fetal pairing to analyze the transmission trend of the allele between the mother and the fetus. However, the results showed that there was no significant difference in the BDNF Val66Met allele and genotype between the two groups, and there was no statistical difference in maternal-fetal transmission of the locus between the two groups, suggesting the Val66Met variant carrying by women with PE dose not transfer to her fetus. Therefore, we can concluded that the poor prognosis of neonates associated with PE may not be related to fetus’ Val66Met polymorphism and we still need to do related research to explore the possible mechanism.
In this study, we found that the SNP at the Val66Met site of BDNF may be related to PE susceptibility. The pregnant women occurring G to A mutation at position 196 have a higher PE susceptibility. Besides, we also proved that BDNF Val66Met may be not related to the poor prognosis of neonates associated with preeclampsia. Therefore, we can conclude that the SNP at the Val66Met may have a potential impact in the occurrence of PE, which provide a possible direction for the treatment,while the reason for poor prognosis of neonates associated with PE still need further study.