Paternal lifestyle as a potential source of germline mutations transmitted to offspring

Abstract

Paternal exposure to high levels of radioactivity causes heritable germline minisatellite mutations. However, the effect of more general paternal exposures, such as cigarette smoking, on germline mutations remains unexplored. We analyzed two of the most commonly used minisatellite loci (CEB1 and B6.7) to identify germline mutations in blood samples of complete mother-father-child triads from the Norwegian Mother and Child Cohort Study (MoBa). The presence of mutations was subsequently related to general lifestyle factors, including paternal smoking before the partner became pregnant. Paternally derived mutations at the B6.7 locus (mutation frequency 0.07) were not affected by lifestyle. In contrast, high gross yearly income as a general measure of a healthy lifestyle coincided with low-mutation frequencies at the CEB1 locus (P=0.047). Income was inversely related to smoking behavior, and paternally derived CEB1 mutations were dose dependently increased when the father smoked in the 6 mo before pregnancy, 0.21 vs. 0.05 in smoking and nonsmoking fathers, respectively (P=0.061). These results suggest that paternal lifestyle can affect the chance of heritable mutations in unstable repetitive DNA sequences. To our knowledge, this is the first study reporting an effect of lifestyle on germline minisatellite mutation frequencies in a human population with moderate paternal exposures.

Father’s environment before conception and asthma risk in his children: a multi-generation analysis of the Respiratory Health In Northern Europe study

“…Smoking is known to cause genetic and epigenetic damage to spermatozoa, which are transmissible to offspring and have the potential to induce developmental abnormalities. 4,5,7,9,[24][25][26][27][28][29] In utero smoking exposure of fathers could influence primordial germ cell development. 3 A prepubertal vulnerability window could be related to de novo DNA methylation occurring during primordial germ cell differentiation to spermatogonia.…”

Single-molecule PCR analysis of an unstable microsatellite for detecting mutations in sperm of mice exposed to chemical mutagens

“…We also recommend that additional dose-response studies and analysis of other mutagens be conducted to establish fully the sensitivity of the assay for germ-cell mutation analysis. This method can be applied potentially to environmental biomonitoring using sentinel species and to human populations to assess the effects of variables that influence heritable mutagenesis [1,4,33,[60][61][62][63][64][65][66]. Our new method expands our ability to detect mutations in germ cells, but we must consider the diverse types of mutation mechanisms and continue to expand the mutational landscape that we can capture in toxicological screening [67].…”

“…There is growing recognition that environmental and lifestyle variables may contribute to increased heritable-mutation burden and adverse effects in the descendants of exposed males [1][2][3][4][5]. Applications of high-throughput genomics technologies in human Abbreviations: ESTRs, expanded simple tandem repeats; SM-PCR, singlemolecule PCR; ENU, N-ethyl-N-nitrosourea; BaP, benzo[a]pyrene; TGR, transgenic rodent gene mutation assay.…”

The protein and transcript profiles of human semen

“…Potential regulatory roles during fertilization and embryogenesis have been suggested for the collection of ncRNAs including confrontation and consolidation of the maternal and paternal genome during fertilization (reviewed in Bourc'his and Voinnet 2010; Krawetz et al 2011;Jodar et al 2013). Several recent studies have suggested that environmental changes may be transmitted to the offspring through spermatozoa, influencing their fertility or health (reviewed in Ng et al 2010;Rando 2012;Linschooten et al 2013;Selvaraju et al 2014). These include a predisposition to diabetes or perhaps even depression in the offspring which can reflect diet or a previous response of the father to traumatic stress (Carone et al 2010;Ng et al 2010;Rando 2012;Gapp et al 2014).…”