Maternal prenatal depression is associated with decreased placental expression of the imprinted gene PEG3.
Maternal prenatal depression is associated with decreased placental expression of the imprinted gene PEG3.
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孕产妇产前抑郁症与印迹基因PEG3的胎盘表达降低有关。
DOI：
10.1017/s0033291716001598
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发表时间：
2016-10
影响因子：
6.9
通讯作者：
John, R. M.
中科院分区：
文献类型：
--
作者：
Janssen, A. B.;Capron, L. E.;O'Donnell, K.;Tunster, S. J.;Ramchandani, P. G.;Heazell, A. E. P.;Glover, V.;John, R. M.
妊娠期母体产前应激与胎儿生长受限和不良神经发育结局相关，这可能由胎盘功能受损介导。印记基因控制胎儿生长、胎盘发育、成年行为（包括母体行为）和胎盘催乳素的产生。本研究旨在探讨母体产前抑郁是否与胎盘印迹基因的异常表达有关，这些印迹基因包括父系表达基因3（PEG3）、父系表达基因10（PEG10）、普列克底物蛋白同源样结构域家族成员2（PHLDA 2）和细胞周期蛋白依赖性激酶抑制剂1C（CDKN 1C），并导致胎盘人胎盘催乳素（hPL）表达受损。从曼彻斯特队列参与者的医疗记录（n = 75）中记录了妊娠期间抑郁症的诊断。夏洛特女王（n = 40）和我的宝贝和我的研究（MBAM）（n = 81）队列参与者完成了爱丁堡产后抑郁量表自评心理测量问卷。绒毛滋养层组织样品进行了基因表达分析。在一项初步研究中，妊娠期间诊断的抑郁症与胎盘PEG 3表达的显著降低相关（41%，p = 0.02）。在另外两个独立的队列中，夏洛特女王和MBAM队列，胎盘PEG 3表达也与母体抑郁评分呈负相关，这种相关性在男性而非女性胎盘中显著。最后，临床诊断为抑郁症的女性（44%，p < 0.05）和抑郁评分高的女性（分别为31%和21%）的hPL表达显著降低。这项研究提供了第一个证据表明，母亲产前抑郁症与胎盘PEG3表达的变化有关，与hPL表达的减少同时发生。这种异常的胎盘基因表达可以为母体抑郁、胎儿生长受限、母体行为受损和后代结局较差的共同发生提供可能的机制解释。
Maternal prenatal stress during pregnancy is associated with fetal growth restriction and adverse neurodevelopmental outcomes, which may be mediated by impaired placental function. Imprinted genes control fetal growth, placental development, adult behaviour (including maternal behaviour) and placental lactogen production. This study examined whether maternal prenatal depression was associated with aberrant placental expression of the imprinted genes paternally expressed gene 3 (PEG3), paternally expressed gene 10 (PEG10), pleckstrin homology-like domain family a member 2 (PHLDA2) and cyclin-dependent kinase inhibitor 1C (CDKN1C), and resulting impaired placental human placental lactogen (hPL) expression. A diagnosis of depression during pregnancy was recorded from Manchester cohort participants’ medical notes (n = 75). Queen Charlotte's (n = 40) and My Baby and Me study (MBAM) (n = 81) cohort participants completed the Edinburgh Postnatal Depression Scale self-rating psychometric questionnaire. Villous trophoblast tissue samples were analysed for gene expression. In a pilot study, diagnosed depression during pregnancy was associated with a significant reduction in placental PEG3 expression (41%, p = 0.02). In two further independent cohorts, the Queen Charlotte's and MBAM cohorts, placental PEG3 expression was also inversely associated with maternal depression scores, an association that was significant in male but not female placentas. Finally, hPL expression was significantly decreased in women with clinically diagnosed depression (44%, p < 0.05) and in those with high depression scores (31% and 21%, respectively). This study provides the first evidence that maternal prenatal depression is associated with changes in the placental expression of PEG3, co-incident with decreased expression of hPL. This aberrant placental gene expression could provide a possible mechanistic explanation for the co-occurrence of maternal depression, fetal growth restriction, impaired maternal behaviour and poorer offspring outcomes.