Differential expression of human placental neurotrophic factors in preterm and term deliveries

Abstract

Neurotrophic factors such as brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are involved in development of the placenta and fetal brain. A series of human and animal studies in our department have shown that micronutrients (folic acid, vitamin B12) and omega 3 fatty acids like DHA are all interlinked in the one carbon cycle. Any alterations in one carbon components will lead to changes in methylation patterns that further affect the gene expression at critical periods of development resulting in complications during pregnancy. This may further contribute to risk for neurodevelopmental disorders in children born preterm. Therefore this study for the first time examines the mRNA levels from preterm and term placentae. A total number of 38 women delivering preterm (<37 weeks gestation) and 37 women delivering at term (=>37 weeks gestation) were recruited. The mRNA levels of BDNF and NGF were analyzed by real time quantitative polymerase chain reaction. Our results indicate that BDNF and NGF mRNA levels were lower in preterm group as compared to term group. There was a positive association of placental BDNF and NGF mRNA levels with cord plasma BDNF and NGF levels. The differential expression of BDNF and NGF gene in preterm placentae may also alter the vascular development in preterm deliveries. Our data suggests that the reduced mRNA levels of BDNF and NGF may possibly be a result of altered epigenetic mechanisms and may have an implication for altered fetal programming in children born preterm.

Maternal Factors that Induce Epigenetic Changes Contribute to Neurological Disorders in Offspring

“…The placenta has also been shown to be affected by several maternal factors, leading to abnormal epigenetic regulation of various developmental genes such as LINE-1 and AluYb8, which in turn may result in neurodevelopmental disorders in the offspring [9]. During pre-term deliveries, significantly lower levels of the two most prominent neurotrophic factors, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), were detected in the placental tissue and umbilical cord plasma, suggesting plausible altered epigenetic mechanisms that could lead to altered fetal programming [10]. …”

Environment, Epigenetic, and Disease: The Modifiable Trilogy

“…The condition of these developmental genes is an essential property of the mammalian germ-line nucleus, allowing differentiated gametes to stimulate the initiation of a totipotent program following fertilization. This totipotent program provides the basis for the embryo and extra-embryonic tissue (Dhobale et al 2013 ).…”

“…Brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are involved in the development of the placenta and fetal brain at the onset of the gestation period (Dhobale et al 2013 ). Before fetal maturation can occur, the placenta joins the fetus to the uterine wall allowing gas and nutrient exchange as well as waste elimination through maternal blood supply.…”

“…Such alterations have been associated with lower concentrations of BDNF and NGF mRNA in preterm placentae. These relatively low concentrations affect gene expression at critical periods of development, resulting in complications during pregnancy which may contribute to risk for neurodevelopmental disorders as well as poor vascular development in children born preterm (Dhobale et al 2013 ).…”

Neurotrophins: Role in adverse pregnancy outcome

“…BDNF in preterm delivery (Dhobale et al, 2012b). The lower placental BDNF and NGF mRNA levels in the preterm deliveries suggesting that the lower mRNA levels of BDNF and NGF may possibly be a result of altered epigenetic mechanisms (Dhobale et al, 2013).…”