Placental contribution to the origins of sexual dimorphism in health and diseases: sex chromosomes and epigenetics

Biology of Sex Differences

Anne Gabory⁵  Tessa J Roseboom⁴  Tom Moore²  Lorna G Moore³  Claudine Junien¹ 

[1] UVSQ, Université Versailles Saint-Quentin en Yvelines, Guyancourt, France

[2] Department of Biochemistry, Biosciences Institute, University College Cork, College Road, Cork, Ireland

[3] Department of Obstetrics and Gynecology, University of Colorado Denver, Aurora, CO, USA

[4] Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, the Netherlands

[5] INRA, UMR1198 Biologie du Développement et Reproduction, Jouy-en-Josas, F-78352, France

关键词: Sexual dimorphism;    Fetal programming;    Environment;    DOHaD;    Nutrition;    DNA methylation;    Histone modifications;    Epigenetics;   

Others  :  793289
DOI  :  10.1186/2042-6410-4-5

 received in 2012-11-02, accepted in 2013-03-04,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Gabory et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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