“Let’s Talk about Sex” was an apt title for a discussion made more complex by a paucity of toxicological and clinical data and several heavily weighted assumptions. The discussion held by the speakers of the “Let’s Talk about Sex—Through the Lenses of a Toxicologist” Workshop Session during the SOT 61st Annual Meeting and ToxExpo leaned heavily on establishing model relevance in the context of real-world conditions while also subverting some popular assumptions, ranging from addressing the effect of tissue signaling on sex determination, sexual dimorphism in organ function, and differences in the real-world environment that change the way men and women are exposed to and expose themselves to toxicants.
Dr. Cheryl Rosenfeld acknowledged several variables that contribute to sex-specific toxicant response, including genetics, presence of hormone-producing sex organs, systemic hormone production and recognition, and signaling in the brain, points of discussion that were mirrored in the talks of each speaker. In pursuit of the guiding factors in sex signaling, Dr. Rosenfeld more specifically spoke on the interplay between the brain and placenta and which hormones drive sex determination and maturation, subverting previous assumptions regarding the muted role of the placenta and signaling in the developing brain.
Dr. Jennifer Schlezinger spoke on the role of PFAS in driving increased serum cholesterol and cholesterol transformation associated with risk for atherogenic dyslipidemia and the importance of the humanized mice model due to the differential activation of PPARα by PFAS between humans and rodents.
Dr. Judith Zelikoff explained the global differences between male and female consumption of e-cigarettes and in the consumption of media inspiring e-cigarette use, differences in nicotine metabolism leading to perceived emotional and biological benefits that promote smoking long-term, and the ways in which smoke leads to similar altered immune, inflammation, and behavioral function across males and females.
Overall, there were several different ways in which the speakers adapted existing experimental paradigms to better answer questions regarding toxicant response in males and females. However, there are several questions that remain unaddressed, especially with regard to incorporation and analysis of sexually dimorphic biology into in vitro assays and NAMs. With more time and data, these approaches can integrate into the existing methodology and improve translational in vitro and in silico approaches as we endeavor to prevent sex and gender bias in research.
This blog was prepared by an SOT Reporter and represents the views of the author. SOT Reporters are SOT members who volunteer to write about sessions and events in which they participate during the SOT Annual Meeting and ToxExpo. SOT does not propose or endorse any position by posting this article. If you are interested in participating in the SOT Reporter program in the future, please email Giuliana Macaluso.
On-demand recordings of all Featured and Scientific Sessions delivered during the 2022 SOT Annual Meeting and ToxExpo will be available to meeting registrants in the SOT Event App and Online Planner after their conclusion, through July 31, 2022.
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