Placental uptake and metabolism of 25(OH)vitamin D determine its activity within the fetoplacental unit.
Placental uptake and metabolism of 25(OH)vitamin D determine its activity within the fetoplacental unit.
复制标题
DOI：
10.7554/elife.71094
复制
发表时间：
2022-03-08
期刊：
影响因子：
7.7
通讯作者：
Cleal JK
中科院分区：
文献类型：
--
作者：
Ashley B;Simner C;Manousopoulou A;Jenkinson C;Hey F;Frost JM;Rezwan FI;White CH;Lofthouse EM;Hyde E;Cooke LDF;Barton S;Mahon P;Curtis EM;Moon RJ;Crozier SR;Inskip HM;Godfrey KM;Holloway JW;Cooper C;Jones KS;Lewis RM;Hewison M;Garbis SDD;Branco MR;Harvey NC;Cleal JK
怀孕25-羟基维生素D [25（OH）D]浓度与母体和胎儿健康结果有关。使用生理人胎盘灌注和绒毛外植体，我们研究了胎盘在调节母体25（OH）D与胎儿生理学之间的关系中的作用。我们证明了通过内吞作用的25（OH）D3的活跃胎盘摄取，胎盘代谢25（OH）D3成24,25-二羟基乙他蛋白D3和活性1,25-二羟基维他命D [1,25（OH）2d3]，随后释放这些代谢物中的母体和胎儿循环。 25（OH）D3的主动胎盘运输和1,25（OH）2D3的合成表明胎儿供应取决于胎盘功能，而不是仅仅取决于胎盘功能，而不是孕妇25（OH）D3的可用性。我们证明25（OH）D3暴露会引起对胎盘转录组和蛋白质组的快速影响。这些映射到胎盘功能中心的多个途径，从而与维生素D转移无关。我们的数据表明，潜在的表观遗传景观有助于决定对维生素D治疗的转录反应。这是第一个定量研究，证明了人胎盘的维生素D转移和代谢，对胎盘本身产生了广泛的影响。这些数据表明，维生素D与胎盘之间存在复杂的相互作用，并将使用维生素D进行胎儿发育和孕产妇适应妊娠的适应性措施。
Pregnancy 25-hydroxyvitamin D [25(OH)D] concentrations are associated with maternal and fetal health outcomes. Using physiological human placental perfusion and villous explants, we investigate the role of the placenta in regulating the relationships between maternal 25(OH)D and fetal physiology. We demonstrate active placental uptake of 25(OH)D3 by endocytosis, placental metabolism of 25(OH)D3 into 24,25-dihydroxyvitamin D3 and active 1,25-dihydroxyvitamin D [1,25(OH)2D3], with subsequent release of these metabolites into both the maternal and fetal circulations. Active placental transport of 25(OH)D3 and synthesis of 1,25(OH)2D3 demonstrate that fetal supply is dependent on placental function rather than simply the availability of maternal 25(OH)D3. We demonstrate that 25(OH)D3 exposure induces rapid effects on the placental transcriptome and proteome. These map to multiple pathways central to placental function and thereby fetal development, independent of vitamin D transfer. Our data suggest that the underlying epigenetic landscape helps dictate the transcriptional response to vitamin D treatment. This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta, with widespread effects on the placenta itself. These data demonstrate a complex interplay between vitamin D and the placenta and will inform future interventions using vitamin D to support fetal development and maternal adaptations to pregnancy.
影响因子：
--
作者：
Desforges, Michelle;Whittaker, Hannah;Farmer, Etaoin;Sibley, Colin P.;Greenwood, Susan L.
通讯作者：
Greenwood, Susan L.