Sex-specific, Male-line Transgenerational Responses in Humans

Marcus Pembrey
Institute of Child Health; UCL


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. We have reported earlier historical associations of longevity with paternal ancestors' food supply in the slow growth period (SGP) in mid childhood (Bygren LO et al 2001, Kaati G et al 2002).


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 Ã�verkalix 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 �verkalix data; paternal grandfather's food supply was only linked to the mortality RR of grandsons, whilst 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.


Sex-specific, male-line transgenerational responses exist in humans and we 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.