November 19, 2019

E-cigarette exposure in pregnant mice delays implantation and reduced weight gain in female offspring

In a recent blog we reported work by Judith Zelicoff of NYU that pregnant mice exposed to e-cigarette vapor developed neuroinflammation and cytokine expression in the brains of offspring and altered memory function and emotional processing in these pups.  Now we report another study demonstrating the adverse reproductive impact of e-cigarette vapors.  Margeaux Wetendorf, PhD , a winner of a 2018 Campion Fund Award and member of Kathleen Caron’s laboratory, University of North Carolina, Chapel Hill, has published a paper demonstrating the C57BL6J strain of mice exposed to e-cigarette vapor five times a week for four months exhibited significantly impaired embryo implantation in the uterus (as there was a nearly complete absence of implantation sites in the exposed animals at day 5.5 of pregnancy).  These animals all had high levels of progesterone an indicator of pregnancy.   Dr. Wetendorf and colleagues then showed by RNA microarray at day 4.5 of gestation in pseudo pregnant mice that there were significant alterations, in the integrin, chemokine and JAK signaling pathways indicating key pathways known to regulate the attachment process -not only in mice, but in humans as well.   A total of 767 genes were differently expressed, 395 upregulated and 372 downregulated.  Successful functioning of the uterine receptive process, well documented to be day 4.5 in mice, and successful implanting of embryos in essential for normal pregnancy.  In a fertility trial conducted as part of these studies, Dr, Wetendorf and colleagues kept the female mice with male mice mating continuously over four consecutive months.  What was of interest is that e-cigarette exposure delayed onset of delivery of the first litter by 3-4 days compared to sham exposed mice.  However, there was no difference in time between subsequent onset of subsequent litters.

The health of the offspring was accessed by mating the offspring of exposed female mice at age 8 to 12 weeks and observing the F2 generation.   There was a slight reduction in fertility and offspring weight and number of the males of litters exposed in utero to e-cigarette vapor.  Females from e-cigarette exposed pregnant mice did not demonstrate reproductive impairment but they were significantly smaller in body weight at 8.5 months of age compared to sham-exposed mice (P=0.006). These findings raise awareness and cause concern that the use of e-cigarettes by pregnant women is not a safe alternative to a traditional tobacco cigarette.   It provides additional data suggesting that genetic and epigenetic programs affect metabolic dysregulation and may be initiated by in utero exposure to various substances.  Thus, clinical studies in humans are important to conduct.  Until definitive studies are performed it is necessary to be very cautious about the use of e-cigarettes during pregnancy in women.

Wetendorf M, Randall LT, Lemma MT, Hurr SH, Pawlak JB, Tarran R, Doerschuk CM, Caron KM. E-Cigarette exposure delays implantation and causes reduced weight gain in female offspring exposed in utero. Journal of the Endocrine Society. 2019 3 (10) 1907: 1016.