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.