It’s well known that maternal experience, such as diet, exercise, and stress during gestation, shapes fetal development and can have lasting impact on the offspring's overall physiology and health. For example, several studies indicate that prenatal exposure to disasters such as the Chernobyl nuclear accident, the September 11th attacks on the World Trade Center, or Hurricane Katrina, contribute to birth defects, alter birth weight, or affect post-partum mother-infant behavior (Harvill et al. 2010). Strikingly, similar experiences contributed from the paternal side also can influence fetal development. In contrast to maternal stress, which impacts developing fetuses in utero, paternal stress is marked in the sperm well before conception occurs, and, as demonstrated in a study from Emory University, may affect multiple generations (Dias and Ressler 2014).
In their study, the Emory researchers tested whether fear conditioning of F0 male mice could influence F1 offspring neuroanatomy. C57BL/6J (000664) and M71 odorant receptor LacZ reporter mice (M71-IRES-tauLacZ, 006675) were presented acetophenone, an odorant that stimulates M71 olfactory sensory neurons, and were then given a mild foot shock. After F0 males learned to associate the odor with fear, they were mated to females. Resulting F1 offspring that were naive to both the odor and the fear conditioning were more sensitive at detecting acetophenone than propanol, a control odorant that does not stimulate M71 neurons. Both the number and size of lacZ-positive M71 neurons were increased in F1 mice from acetophenone F0 fathers compared to these neurons in F1 mice descended from unconditioned F0 fathers or from F0 fathers conditioned to propanol.
Interestingly, F1 mice generated by in vitro fertilization using sperm from conditioned fathers, as well as F2 mice from acetophenone -naive F1 fathers who were descended from conditioned F0 fathers, both developed larger and more numerous M71 neurons. These results indicate that odorant sensitivity is transmitted genetically, rather than behaviorally. To explore the genetic mechanism for transmitting odorant sensitivity, DNA was isolated from conditioned F0 male sperm and subjected to bisulfite sequencing. The Olfr151 locus, which encodes the M71 odorant receptor, was found to be hypomethylated, suggesting increased gene transcription. These results indicate that odorant fear conditioning causes epigenetic changes to the DNA that can be passed on to future generations and may alter gene expression in the olfactory epithelium.
Together with other research on the influence of paternal diet on offspring metabolism (Wei et al. 2015), this study brings attention to an important relationship between father and offspring: namely, that paternal lifestyle during spermatogenesis and sperm maturation can affect fetal development just as maternal lifestyle can during gestation.