A transdisciplinary approach to evaluate the effects of wildfire smoke on fertility

Wildfires have become more frequent and intense over the last four decades. Due to the burning of both biomass and human-made structures during wildfires, the particulate matter generated from wildfire smoke (WFPM) tends to have smaller particle sizes and contain a unique mixture of chemicals that may be more toxic than urban background PM2.5, which is mostly generated from the fossil fuel combustion. Of particular concern is the presence of more polar and higher oxidative organic compounds, such as polycyclic aromatic hydrocarbons (PAHs), which could lead to a host of adverse consequences including effects on human fertility. As wildfires become more pervasive, it is imperative to understand how they affect female reproductive function. To address this knowledge gap, we propose to develop a transdisciplinary consortium to explore a set of integrated aims using population, clinical, and experimental approaches to investigate the association between wildfire smoke and female fertility. Aim 1 will utilize population-level data from the National Assisted Reproductive Technology (ART) Surveillance System, which includes over 220,000 ART cycles initiated in Western US states from 2001 to 2019, to evaluate the impact of WFPM on probability of cycle cancellation, clinical pregnancy, and live birth. Aim 2 will leverage a unique clinical biorepository of ART patients at UCSF who underwent oocyte retrieval during a period of pristine air quality (May-Jul 2020) and record-setting wildfires (Sep-Nov 2020) to determine the impacts of WFPM on ovarian reserve, oocyte and embryo quality, and the chemical composition of the follicular fluid. Finally, Aim 3 will use a state-of-the-art, lab-based wildfire simulator to experimentally evaluate the effects of whole-body WFPM on ovarian function and reproductive outcomes in mice. Moreover, an established ex vivo 3D ovarian follicle culture system will be used to investigate the toxic mechanisms of human relevant exposure levels of WFPM on folliculogenesis and oogenesis. We expect the clinical and biological insights gained from this proposal will provide valuable information for individual- and population-level prevention, clinical decision making, future risk assessments and policy decisions, with the longer-term goal of reducing female infertility.