Determinants of brain-derived neurotrophic factor (BDNF) in umbilical cord and maternal serum

Flöck, A; Weber, Sarah K.; Ferrari, Nina; Fietz, Cornelia; Gräf, Christine; Fimmers, Rolf; Gembruch, Ulrich; Merz, Waltraut M.

doi:10.1016/j.psyneuen.2015.09.028

Cited by 35 publications

(29 citation statements)

References 36 publications

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“…Compared to controls, women with PCOS had higher IL6 levels and comparable levels of IL15, BDNF, and NGF in peripheral blood. Female newborns of women with PCOS had comparable IL6 and IL15 levels but significantly lower levels of BDNF and NGF in umbilical cord blood compared to those of control women, which is in accordance with a previous study that reported that neural factors are unlikely to traffic between foetus and mother [ 60 ].…”

Section: Resultssupporting

confidence: 91%

Molecular mechanisms underlying altered neurobehavioural development of female offspring of mothers with polycystic ovary syndrome: FOS-mediated regulation of neurotrophins in placenta

et al. 2020

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Background This study explored the mechanisms underlying altered neurobehavioural development of female offspring born to mothers with polycystic ovary syndrome (PCOS). Methods In total, 20 women with PCOS and 32 healthy women who underwent caesarean deliveries with a single female foetus were recruited. Infants were assessed with Dubowitz scoring. Swan71 cell line with stable FOS overexpression was used to verify the regulatory effects of FOS on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) expression. Learning and memory in female first-generation (F1) and second-generation (F2) offspring in a rat model of PCOS was tested using the Morris water maze at puberty and adulthood. Transcriptome analysis of pubertal hippocampi and hypothalami of female F1 offspring was conducted. Findings Total score and behaviour subscales of Dubowitz scoring were significantly lower in female infants of women with PCOS. FOS and NGF protein levels were downregulated in placental villi of the PCOS group. FOS played a key role in BDNF inhibition and enhancing NGF in Swan71 cells. PCOS female F1 rats exhibited lower target crossing times during puberty when compared to controls. Transcriptome analysis revealed significant changes in hippocampal and hypothalamic neuronal pathways in female F1 rats at puberty. Interpretation FOS regulation of neurotrophins in the placenta negatively affects neurobehavioural development of female offspring of PCOS mothers. Funding This study was funded by the National Key R&D Program of China (2018YFC1004900 to F.Q. and F.W.) and the National Natural Science Foundation of China (81874480 to F.Q.; 81873837 to F.W.).

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Section: Resultssupporting

confidence: 91%

Molecular mechanisms underlying altered neurobehavioural development of female offspring of mothers with polycystic ovary syndrome: FOS-mediated regulation of neurotrophins in placenta

et al. 2020

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“…Because of this heterogeneity, we do not assume that BDNF methylation in peripheral tissues is the same as in a particular brain region. Nevertheless, examining BDNF methylation in these tissues is relevant for prenatal development as BDNF plays a role in placental and fetal growth [7] and BDNF protein levels in the periphery are associated with birth outcomes [23–25]. Recent research has documented several types of prenatal exposures, including air pollution and nicotine use, are associated with placental BDNF methylation [84, 85].…”

Section: Discussionmentioning

confidence: 99%

BNDF methylation in mothers and newborns is associated with maternal exposure to war trauma

et al. 2017

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BackgroundThe BDNF gene codes for brain-derived neurotrophic factor, a growth factor involved in neural development, cell differentiation, and synaptic plasticity. Present in both the brain and periphery, BDNF plays critical roles throughout the body and is essential for placental and fetal development. Rodent studies show that early life stress, including prenatal stress, broadly alters BDNF methylation, with presumed changes in gene expression. No studies have assessed prenatal exposure to maternal traumatic stress and BDNF methylation in humans. This study examined associations of prenatal exposure to maternal stress and BDNF methylation at CpG sites across the BDNF gene.ResultsAmong 24 mothers and newborns in the eastern Democratic Republic of Congo, a region with extreme conflict and violence to women, maternal experiences of war trauma and chronic stress were associated with BDNF methylation in umbilical cord blood, placental tissue, and maternal venous blood. Associations of maternal stress and BDNF methylation showed high tissue specificity. The majority of significant associations were observed in putative transcription factor binding regions.ConclusionsThis is the first study in humans to examine BDNF methylation in relation to prenatal exposure to maternal stress in three tissues simultaneously and the first in any mammalian species to report associations of prenatal stress and BDNF methylation in placental tissue. The findings add to the growing body of evidence highlighting the importance of considering epigenetic effects when examining the impacts of trauma and stress, not only for adults but also for offspring exposed via effects transmitted before birth.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-017-0367-x) contains supplementary material, which is available to authorized users.

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“…57 Accordingly, we demonstrated in a previous human study that umbilical cord BDNF is correlated with maternal BDNF, although the correlation was weak. 58 Animal models using different exercise protocols already demonstrated that maternal exercise during pregnancy has beneficial effects on the development and cognitive function of the offspring brain. 11,59 Our study observed three-fold higher serum BDNF levels in the offspring of exercised mothers (INT m ) compared with CO m .…”

Section: Effects Of Maternal Exercise On Adult Offspring Without Hfdmentioning

confidence: 99%

Exercise during pregnancy and its impact on mothers and offspring in humans and mice

Ferrari

Bae‐Gartz

Bauer

et al. 2017

J Dev Orig Health Dis

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Exercise during pregnancy has beneficial effects on maternal and offspring's health in humans and mice. The underlying mechanisms remain unclear. This comparative study aimed to determine the long-term effects of an exercise program on metabolism, weight gain, body composition and changes in hormones [insulin, leptin, brain-derived neurotrophic factor (BDNF)]. Pregnant women (n=34) and mouse dams (n=44) were subjected to an exercise program compared with matched controls (period I). Follow-up in the offspring was performed over 6 months in humans, corresponding to postnatal day (P) 21 in mice (period II). Half of the mouse offspring was challenged with a high-fat diet (HFD) for 6 weeks between P70 and P112 (period III). In period I, exercise during pregnancy led to 6% lower fat content, 40% lower leptin levels and an increase of 50% BDNF levels in humans compared with controls, which was not observed in mice. After period II in humans and mice, offspring body weight did not differ from that of the controls. Further differences were observed in period III. Offspring of exercising mouse dams had significantly lower fat mass and leptin levels compared with controls. In addition, at P112, BDNF levels in offspring were significantly higher from exercising mothers while this effect was completely blunted by HFD feeding. In this study, we found comparable effects on maternal and offspring's weight gain in humans and mice but different effects in insulin, leptin and BDNF. The long-term potential protective effects of exercise on biomarkers should be examined in human studies.

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Determinants of brain-derived neurotrophic factor (BDNF) in umbilical cord and maternal serum

Cited by 35 publications

References 36 publications

Molecular mechanisms underlying altered neurobehavioural development of female offspring of mothers with polycystic ovary syndrome: FOS-mediated regulation of neurotrophins in placenta

Molecular mechanisms underlying altered neurobehavioural development of female offspring of mothers with polycystic ovary syndrome: FOS-mediated regulation of neurotrophins in placenta

BNDF methylation in mothers and newborns is associated with maternal exposure to war trauma

Exercise during pregnancy and its impact on mothers and offspring in humans and mice

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