Placental contribution to the origins of sexual dimorphism in health and diseases: sex chromosomes and epigenetics.
Placental contribution to the origins of sexual dimorphism in health and diseases: sex chromosomes and epigenetics.
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DOI：
10.1186/2042-6410-4-5
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发表时间：
2013-03-21
影响因子：
7.9
通讯作者：
Junien C
中科院分区：
文献类型：
--
作者：
Gabory A;Roseboom TJ;Moore T;Moore LG;Junien C
大多数非传染性疾病都存在性别差异，包括代谢性疾病、高血压、心血管疾病、精神和神经紊乱以及癌症。在许多情况下，对这些疾病的易感性在发育早期就开始了。所观察到的两性差异可能是由于遗传和激素的差异以及对环境因素（包括感染、饮食、药物和压力）的反应和相互作用的差异造成的。胎盘在胎儿的生长发育中起着关键作用，因此，它影响了胎儿的编程，从而影响了随后的成人健康，并部分解释了健康和疾病的发育起源（DOHaD）。越来越多的证据表明，不同环境对胎盘功能的影响与生命后期疾病风险之间存在性别特异性关系。作为人类少数容易收集的组织之一，这个器官可能因此被视为研究男性和女性胎盘如何感知营养和其他压力（如内分泌干扰物）的理想系统。控制不同器官两性二态特征的性别特异性调节途径，以及性激素表达终生差异的后果，在很大程度上解释了这种反应。然而，表观遗传标记的性别特异性变化是在受精后早期产生的，因此在没有性激素的情况下，在肾上腺和性腺分化之前，以及对环境条件的反应。考虑到参与胎盘发生的X连锁基因的丰富程度，以及男性和女性之间性染色体早期不平等的基因表达，X和y染色体连锁基因的作用，特别是那些参与特殊胎盘特异性表观遗传过程的基因，引起了不寻常的胎盘表观遗传景观，值得特别关注。然而，即使在这一领域有了最新的发展，我们仍然对早期性别特异性表观遗传标记导致性别偏向的基因表达途径和网络的机制知之甚少。作为母体环境和胎儿之间的重要信使，胎盘可能不仅在缓冲母亲传递的环境影响方面发挥关键作用，而且在母体和父亲在孕前暴露于压力条件下的表达和调节作用中发挥关键作用。
Sex differences occur in most non-communicable diseases, including metabolic diseases, hypertension, cardiovascular disease, psychiatric and neurological disorders and cancer. In many cases, the susceptibility to these diseases begins early in development. The observed differences between the sexes may result from genetic and hormonal differences and from differences in responses to and interactions with environmental factors, including infection, diet, drugs and stress. The placenta plays a key role in fetal growth and development and, as such, affects the fetal programming underlying subsequent adult health and accounts, in part for the developmental origin of health and disease (DOHaD). There is accumulating evidence to demonstrate the sex-specific relationships between diverse environmental influences on placental functions and the risk of disease later in life. As one of the few tissues easily collectable in humans, this organ may therefore be seen as an ideal system for studying how male and female placenta sense nutritional and other stresses, such as endocrine disruptors. Sex-specific regulatory pathways controlling sexually dimorphic characteristics in the various organs and the consequences of lifelong differences in sex hormone expression largely account for such responses. However, sex-specific changes in epigenetic marks are generated early after fertilization, thus before adrenal and gonad differentiation in the absence of sex hormones and in response to environmental conditions. Given the abundance of X-linked genes involved in placentogenesis, and the early unequal gene expression by the sex chromosomes between males and females, the role of X- and Y-chromosome-linked genes, and especially those involved in the peculiar placenta-specific epigenetics processes, giving rise to the unusual placenta epigenetic landscapes deserve particular attention. However, even with recent developments in this field, we still know little about the mechanisms underlying the early sex-specific epigenetic marks resulting in sex-biased gene expression of pathways and networks. As a critical messenger between the maternal environment and the fetus, the placenta may play a key role not only in buffering environmental effects transmitted by the mother but also in expressing and modulating effects due to preconceptional exposure of both the mother and the father to stressful conditions.