September 10, 2019

Air pollution harms reproductive health meeting June 1, 2019. Number 3 in the series

Jungfeng Zhang, Professor, Duke Global Health Institute and Nicolas School of the Environment, explained that identifying pregnancy time windows during which environment exposures impact fetal development is central to understanding the mechanisms leading to the impacts on infants and children.  Some studies report associations between low birth weight and air pollution exposure. During the 2008 Olympics held in Beijing August 8-24, air pollution levels were substantially lower than during the same time periods of 2007 and 2009.  He presented a study he and his colleagues conducted analyzing 80,246 births with at least I month of pregnancy occurring during these calendar dates.  Babies whose 8th month of gestation during the 2008 Olympics were on average 23 g. heavier than those babies born during the same dates in 2007 and 2009.  The scientists found that increased PM2.5, CO2, So2 and NO2 concentrations during the 8th month of pregnancy were associated with decreased birth weight. No significant association occurred during earlier gestational months. Thus, even short-term decreased in air pollution in late pregnancy can have beneficial effects on birth weight.  Dr. Zhang and colleagues are currently conducting a prospective cohort study of 660 women in China.  They hypothesize that maternal inflammatory responses to air pollution adversely impacts the development and transport of the placenta, increase placental inflammation altering placenta growth, vascular branching, hormone and growth factor levels.  This response may result in an inflammatory response in the fetus and reduced nutrient delivery from the mother across the placenta. Imprinted genes may also be impacted by these responses and play a role in placental function.  In this cohort study, links between individual-level gestational month specific pollutant concentrations and pathological responses and birth weight will be determined.

Judith Zelikoff, Professor of Environmental Medicine, NYU Langone School of Medicine, presented studies conducted in pregnant female mice exposed to air pollution.   Research in mice as a model of human pathology is extremely important in general, but especially so in reproductive biology.  These studies help understand the mechanisms of poor health conditions as the life span of mice is shorter than that of humans and thus studies of multiple generations can be carried out within reasonable time frames and long-term intergenerational impacts may be observed. In well designed studies groups of exposed mice are compared to control, unexposed mice.  Dr. Zelikoff presented data showing that prenatal e-cigarette aerosol exposure to female pregnant mice showed substantial evidence of neuroinflammation and cytokine expression in the brains of female and male offspring.  Furthermore, altered behavior, including learning and memory function and emotional processing was found in these offspring compared to those of control mice.  In a study where pregnant mice were exposed to particulate matter air pollution and compared to control animals, this exposure was associated with low birth weight and preterm birth, in gestational specific window of time.  Exposure to air pollution lead to alterations in adult offspring behavior associated with an autism-like phenotype.  Dr. Zelikoff also presented a study of gene expression in mouse placentae which demonstrated an association between preterm birth linked genes and PM2.5 exposure.  Six genes (ace, Ddah1, Col1a2, Chst15, Akap12, Ephx1) were downregulated and one gene (Chys3) was upregulated.  Thus, particulate matter exposure influences the placental genome.

Carol Readhead, PhD, Research Associate, California Institute of Technology, discussed the impact of winter air pollution in Ulaanbaatar, Mongolia on conception.  This city is the coldest capital city in the world, with January, February temperatures below -40 C.  Coal burning, car exhaust, and dust leads to the worst air pollution on earth, a pollution that is 133 times higher than the WHO recommended safe level.  The records of all 10,715 infants born from January 2014 to December 2015 were analyzed and gestational age calculated to determine the month of conception.  A 2.2- fold decrease in infants conceived in January, the month with the highest atmospheric pollution, compared to June, the month with the lowest levels of pollution.  S02, N02, PM10, and PM 2.5 levels were collected from six Mongolian Air Quality Monitoring Stations in Ulaanbaatar. SO2 had the strongest negative correlation between air pollution and conception rate.

Jeanette Stingone, PhD, MPH, Assistant Professor of Epidemiology, Mailman School of Public Health, Columbia University, explained that while most research on the environmental contributors to reproductive health analyzed toxins singly, a realistic assessment of human exposure needs to incorporate multiple exposures and to consider potential interactions between these exposures.  The totality of exposures (the exposome) from conception through life allows an examination of multiple exposures and their influences on health outcomes.  This conceptual approach can provide powerful insights into windows of susceptibility, analysis of contributors such as climate change and greater investigation of the interplay between parental and offspring exposure during development.

Sarah Berga, MD, Professor and Chief of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Utah, discussed the complex impact of stress and stress hormones on the hypothalamic- pituitary -ovarian axis and how this influences reproductive biology.