Murthi Padma, Davies-Tuck Miranda, Lappas Martha, Singh Harmeet, Mockler Joanne, Rahman Rahana, Lim Rebecca, Leaw Bryan, Doery James, Wallace Euan M, Ebeling Peter R
Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Vic., Australia.
The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Vic., Australia.
Clin Endocrinol (Oxf). 2017 Mar;86(3):401-409. doi: 10.1111/cen.13281. Epub 2016 Dec 19.
Maternal vitamin D deficiency during pregnancy has been linked to impaired neurocognitive development in childhood. The mechanism by which vitamin D affects childhood neurocognition is unclear but may be via interactions with serotonin, a neurotransmitter involved in foetal brain development. In this study, we aimed to explore associations between maternal and foetal vitamin D concentrations, and foetal serotonin concentrations at term.
Serum 25-hydroxyvitamin D (25(OH)D, nmol/l) and serotonin (5-HT, nmol/l) concentrations were measured in maternal and umbilical cord blood from mother-infant pairs (n = 64). Association between maternal 25(OH)D, cord 25(OH)D and cord serotonin was explored using linear regression, before and after adjusting for maternal serotonin levels. We also assessed the effects of siRNA knockdown of the vitamin D receptor (VDR) and administration of 10 nm 1,25-dihydroxyvitamin D on serotonin secretion in human umbilical vein endothelial cells (HUVECs) in vitro.
We observed an inverse relationship between both maternal and cord 25(OH)D concentrations with cord serotonin concentrations. The treatment of HUVECs with 1,25-dihydroxyvitamin D in vitro decreased the release of serotonin (193·9 ±14·8 nmol/l vs 458·9 ± 317·5 nmol/l, control, P < 0·05). Conversely, inactivation of VDR increased serotonin release in cultured HUVECs.
These observations provide the first evidence of an inverse relationship between maternal 25(OH)D and foetal serotonin concentrations. We propose that maternal vitamin D deficiency increases foetal serotonin concentrations and thereby contributes to longer-term neurocognitive impairment in infants and children.
孕期母亲维生素D缺乏与儿童神经认知发育受损有关。维生素D影响儿童神经认知的机制尚不清楚,但可能是通过与血清素相互作用,血清素是一种参与胎儿大脑发育的神经递质。在本研究中,我们旨在探讨足月时母亲和胎儿维生素D浓度与胎儿血清素浓度之间的关联。
测量了母婴对(n = 64)母亲和脐带血中的血清25-羟基维生素D(25(OH)D,nmol/l)和血清素(5-HT,nmol/l)浓度。在调整母亲血清素水平前后,使用线性回归探讨母亲25(OH)D、脐带25(OH)D和脐带血清素之间的关联。我们还评估了维生素D受体(VDR)的siRNA敲低以及10 nM 1,25-二羟基维生素D给药对人脐静脉内皮细胞(HUVECs)体外血清素分泌的影响。
我们观察到母亲和脐带25(OH)D浓度与脐带血清素浓度均呈负相关。体外使用1,25-二羟基维生素D处理HUVECs可降低血清素的释放(193·9 ±14·8 nmol/l对458·9 ± 317·5 nmol/l,对照组,P < 0·05)。相反,VDR失活会增加培养的HUVECs中血清素的释放。
这些观察结果首次证明了母亲25(OH)D与胎儿血清素浓度之间存在负相关。我们提出,母亲维生素D缺乏会增加胎儿血清素浓度,从而导致婴幼儿长期神经认知损害。