August 31, 2019

Air Pollution Harms Reproductive Health Meeting, June 1, 2019. Number 2 in the series of highlights from the meeting.

Male reproductive health is impacted by poor air quality explained Douglas Carrell, PhD, University of Utah, Center for Reproductive Medicine.   He mentioned that previous reports demonstrate that air pollution negatively affects semen quality including sperm chromosome telomere shortening and alter the ratio of sperm containing the X or Y chromosome.  Particulate matter (PM 2.5) found in the Salt Lake Valley region of Utah has been implicated in genetic instability.  This is relevant to sperm quality since there is extensive genetic remodeling during spermatogenesis.  Furthermore, the air pollution associated with the Salt Lake Valley’s temperature inversions correlates with negative change in semen quality two months after air pollution exposure, a fact consistent with the spermatogenesis cycle.  Dr. Carrell then presented the results of a study comparing genome-wide DNA methylation alterations (modifications indicating epigenetic changes in gene expression) and DNA strand breaks (indicating DNA damage) in the sperm in semen analysis of men residing in the Salt Lake Valley region two months after exposure to air pollution and their semen analysis two months after low air pollution.  The controls for the study were the semen analysis of men who resided in rural low air pollution areas of Utah taken at the two time points.  CpG is shorthand for a cytosine and quanine separated by one phosphate group in DNA. These sites occur with high frequency in some areas of the genome and are called CpG islands.  A cytosine can be methylated or demethylated changing gene expression.  The findings of the study were significant and showed that 225 CpG sites of the sperm genes from men residing in the Salt Lake Valley region were differentially methylated after air pollution exposure compared to the sperm DNA of the same men after low air pollution.  Compared to men in rural areas 209 of these CpG sites were differentially methylated. The differentially methylated genes were distributed throughout the genome and tended to be demethylated following air pollution.  Thus, epigenetic alterations in the form of altered DNA methylation was associated with exposure to air pollution.  Given the potential consequences of altered gene expression inherent with epigenetic changes and the possibility of transgenerational inheritance of these epigenetic alterations this study raises serious concerns regarding the health of future generations of children produced as a result of air pollution on male reproduction.  It is important to continue to study this problem in a rigorous manner.

Michelle Debbink, MD, PhD, University of Utah, LDS Hospital and Intermountain Hospital, presented a follow-up study of the outcomes of offspring born during the 13months of Utah County Geneva Steel Mill closure due to a labor strike in 1986.  A previous study demonstrated that during the mill closure when air quality improved the preterm birth rate improved compared to the times immediately before and after the mill closure.  The study Dr. Debbink presented included 75,053 singleton live births greater than 23 weeks gestation in Utah County from August 1981 to September 1992.  The subjects were alive in 2014.  The birth data was linked to 2014 health care data of the subjects. 11,129 births followed in utero exposure to the air at the time of mill closure.  There were no significant differences in birth sex, gestational age, birth weight, maternal age and type of delivery compared to those born during mill operation.  The outcomes studied were medical visits for endocrine, psychiatric, respiratory, reproductive, cardiovascular and autoimmune disorders in adult life.  Exposure in utero was calculated by the number of weeks of the first and second trimester occurring during the time of the mill strike.  Maternal education was utilized as a marker of socioeconomic status.  Interestingly, in utero exposure to mill closure air was associated with increased health care visits, indicating a higher disease burden in this group.  The one exception was that number of visits for cardiovascular disorders was less.  These findings suggest that the economic stress of the mill closure and the significant economic consequences of job loss during the mill strike was associated with the long-term trend of poorer health in these individuals.  However, the improved cardiovascular health assumed by the decrease in cardiovascular disease visits suggested that in utero exposure to cleaner air quality lessened adult cardiovascular disorders.  Greater maternal education was associated with fewer healthcare visits.  What is apparent from this study is that epidemiological studies of air pollution and reproductive health need to be carefully designed, conducted and analyzed to account for all variables that impact on outcomes.

Further reading:

Carrell DT. The sperm epigenome: implications for assisted reproductive technologies. Genetic damage in human spermatogenesis. Adv Exp Med. 2019: 1166: 47-56.

Parker JD, Mendola P, Woodruff TJ.  Preterm birth after the Utah Valley Steel Mill closure: a natural experiment. Epidemiology. 2008. DOI:10.1097/EDE.ob013e318883d5d

Debbink MP, Wong J, Hollinghaus MD, et al.  Long time health effects after in utero exposure to the Geneva Steel Mill closure.  Amer Jour Obstet Gynecol 2019. 220: 1 Suppl S 474.