Gene changes due to maternal smoking more prevalent in males

Male fetuses and adult sons of women who smoke while pregnant exhibit more changes in gene expression than females.

Researchers at the University of Aberdeen conducted two studies – they analysed livers of fetuses from women who had elective pregnancy terminations, and they also investigated the longer-term effects of maternal smoking using data from the UK Biobank. They found that the expression of genes relating to inflammation, liver damage, cancer development and alcohol and drug metabolism was increased in the livers of male fetuses from women who smoked, but decreased in females. The team also found that these effects lasted into adulthood, with adult men whose mothers smoked while pregnant having an increased risk of dying younger. However, this risk was reduced in men who reported to have never smoked themselves.

'Our findings show that maternal smoking impacts baby's health, particularly for males, from as early as the second trimester and this continues throughout adulthood,' said Mihail Mihov, PhD student at the University of Aberdeen and first author of the paper published in eMedicine. 'However, we did find that this can be somewhat reversed. Our results indicate that smoking cessation or, ideally, not smoking at all in men can counter the increased risk of early death in adulthood.'

In the first part of their research, the team analysed 64 fetal livers and found that male fetuses exposed to maternal smoking were more affected than female fetuses, particularly in the later stages of pregnancy. Overall, the expression of 3313 genes was increased in the livers of male fetuses, compared with 1163 in the livers of female fetuses.

In a parallel investigation, the team studied data from over 350,000 middle-aged adults from the UK Biobank. About 30 percent of the participants reported that their mother had smoked at the time of their birth. The researchers conducted phenome-wide, genome-wide and transcriptome-wide association studies to identify genes associated with maternal smoking behaviour, and to see if the differences they saw in gene expression in the livers of male and female fetuses were present in later life.

'We also, for the first time, identified several gene variants which increase the likelihood that a mother will smoke or be addicted to smoking, even during pregnancy,' said Mihov.

The researchers found nine genetic variants that were significantly associated with maternal smoking behaviour, including in genes relating to nicotine addiction and neurodegeneration. The authors note that some of the genetic changes in the male fetal livers were also found in the adult study and conclude they may be influenced by inherited genetic variants. The authors suggest that these genes 'should be examined in more detail to find out their precise function in the context of maternal smoking in utero and their genetic control'.