Rice Frances, Harold Gordon T, Boivin Jacky, Hay Dale F, van den Bree Marianne, Thapar Anita
Department of Psychological Medicine, School of Medicine, Cardiff University, Cardiff CF14 4XN, Wales, United Kingdom.
Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2464-7. doi: 10.1073/pnas.0808798106. Epub 2009 Feb 2.
Exposure to adversity in utero at a sensitive period of development can bring about physiological, structural, and metabolic changes in the fetus that affect later development and behavior. However, the link between prenatal environment and offspring outcomes could also arise and confound because of the relation between maternal and offspring genomes. As human studies cannot randomly assign offspring to prenatal conditions, it is difficult to test whether in utero events have true causal effects on offspring outcomes. We used an unusual approach to overcome this difficulty whereby pregnant mothers are either biologically unrelated or related to their child as a result of in vitro fertilization (IVF). In this sample, prenatal smoking reduces offspring birth weight in both unrelated and related offspring, consistent with effects arising through prenatal mechanisms independent of the relation between the maternal and offspring genomes. In contrast, the association between prenatal smoking and offspring antisocial behavior depended on inherited factors because association was only present in related mothers and offspring. The results demonstrate that this unusual prenatal cross-fostering design is feasible and informative for disentangling inherited and prenatal effects on human health and behavior. Disentangling these different effects is invaluable for pinpointing markers of prenatal adversity that have a causal effect on offspring outcomes. The origins of behavior and many common complex disorders may begin in early life, therefore this experimental design could pave the way for identifying prenatal factors that affect behavior in future generations.
在发育的敏感时期子宫内暴露于逆境会给胎儿带来生理、结构和代谢变化，从而影响其日后的发育和行为。然而，由于母体基因组与后代基因组之间的关系，产前环境与后代结局之间的联系也可能产生并造成混淆。由于人体研究无法将后代随机分配到不同的产前条件下，因此很难检验子宫内事件是否对后代结局具有真正的因果效应。我们采用了一种不同寻常的方法来克服这一困难，即通过体外受精（IVF），让怀孕母亲与孩子在生物学上要么无亲缘关系，要么有亲缘关系。在这个样本中，产前吸烟会降低无亲缘关系和有亲缘关系后代的出生体重，这与通过独立于母体基因组与后代基因组关系的产前机制产生的影响一致。相比之下，产前吸烟与后代反社会行为之间的关联取决于遗传因素，因为这种关联仅在有亲缘关系的母亲和后代中存在。结果表明，这种不同寻常的产前交叉寄养设计对于区分遗传和产前对人类健康及行为的影响是可行且有参考价值的。区分这些不同影响对于确定对后代结局有因果效应的产前逆境标志物非常重要。行为以及许多常见复杂疾病的根源可能始于生命早期，因此这种实验设计可为识别影响后代行为的产前因素铺平道路。
