Sex-specific, male-line transgenerational responses in humans
Sex-specific, male-line transgenerational responses in humans
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DOI：
10.1038/sj.ejhg.5201538
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发表时间：
2006-02-01
影响因子：
5.2
通讯作者：
Golding, J
中科院分区：
文献类型：
--
作者：
Pembrey, ME;Bygren, LO;Golding, J
母亲营养或其他环境“暴露”的跨代影响已得到公认，但很少考虑男性暴露影响下一代发育和健康的可能性。然而，历史协会的长寿与父系祖先的食物供应在缓慢增长期（SGP）在童年中期的报告。使用雅芳父母和儿童纵向研究（ALSPAC），我们确定了166名报告在11岁之前开始吸烟的父亲，并在校正混杂因素后，将其后代的生长与父亲吸烟较晚的后代进行比较。我们分析了食物供应对后代和孙辈死亡风险比（RR）的影响，使用了瑞典北方1890年、1905年和1920年Overkalix队列中的303名先证者及其1818名父母和祖父母。经过适当的调整后，父亲早期吸烟与儿子9岁时更大的体重指数（BMI）相关，但与女儿无关。Overkalix数据还显示了性别特异性效应;祖父的食物供应仅与孙子的死亡率RR相关，而祖母的食物供应仅与孙女的死亡率RR相关。在SGP（祖父母双方）或胎儿/婴儿（祖母）时期的接触中观察到了这些跨代效应，但在祖父母的青春期中没有观察到。我们的结论是，性别特异性，男性线跨代反应存在于人类和假设，这些传输是由性染色体，X和Y介导的。这种反应为研究发育和健康中的基因-环境相互作用增添了一个全新的层面。
Transgenerational effects of maternal nutrition or other environmental 'exposures' are well recognised, but the possibility of exposure in the male influencing development and health in the next generation(s) is rarely considered. However, historical associations of longevity with paternal ancestors' food supply in the slow growth period (SGP) in mid childhood have been reported. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we identified 166 fathers who reported starting smoking before age 11 years and compared the growth of their offspring with those with a later paternal onset of smoking, after correcting for confounders. We analysed food supply effects on offspring and grandchild mortality risk ratios (RR) using 303 probands and their 1818 parents and grandparents from the 1890, 1905 and 1920 Overkalix cohorts, northern Sweden. After appropriate adjustment, early paternal smoking is associated with greater body mass index (BMI) at 9 years in sons, but not daughters. Sex-specific effects were also shown in the Overkalix data; paternal grandfather's food supply was only linked to the mortality RR of grandsons, while paternal grandmother's food supply was only associated with the granddaughters' mortality RR. These transgenerational effects were observed with exposure during the SGP (both grandparents) or fetal/infant life (grandmothers) but not during either grandparent's puberty. We conclude that sex-specific, male-line transgenerational responses exist in humans and hypothesise that these transmissions are mediated by the sex chromosomes, X and Y. Such responses add an entirely new dimension to the study of gene-environment interactions in development and health.