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Sex-Dependent Influence of Developmental Toxicant Exposure on Group B Streptococcus-Mediated Preterm Birth in a Murine Model

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Abstract

Infectious agents are a significant risk factor for preterm birth (PTB); however, the simple presence of bacteria is not sufficient to induce PTB in most women. Human and animal data suggest that environmental toxicant exposures may act in concert with other risk factors to promote PTB. Supporting this “second hit” hypothesis, we previously demonstrated exposure of fetal mice (Fl animals) to the environmental endocrine disruptor 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to an increased risk of spontaneous and infection-mediated PTB in adult animals. Surprisingly, adult FImaes also confer an enhanced risk of PTB to their control partners. Herein, we used a recently established model of ascending group B Streptococcus (GBS) infection to explore the impact of a maternal versus paternal developmental TCDD exposure on infection-mediated PTB in adulthood. Group B Streptococcus is an important contributor to PTB in women and can have serious adverse effects on their infants. Our studies revealed that although gestation length was reduced in control mating pairs exposed to low-dose GBS, dams were able to clear the infection and bacterial transmission to pups was minimal. In contrast, exposure of pregnant Flfemales to the same GBS inoculum resulted in 100% maternal and fetal mortality. Maternal health and gestation length were not impacted in control females mated to FImales and exposed to GBS; however, neonatal survival was reduced compared to controls. Our data revealed a sex-dependent impact of parental TCDD exposure on placental expression of Toll-like receptor 2 and glycogen production, which may be responsible for the differential impact on fetal and maternal outcomes in response to GBS infection.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Women’s Reproductive Health Research Center, Vanderbilt University Medical Center, 1161 21st Ave S MCN B-1100, Nashville, TN, 37232, USA

    Tianbing Ding PhD, Lauren A. Lambert, David M. Aronoff MD, Kevin G. Osteen & Kaylon L. Bruner-Tran PhD

  2. Division of Infectious Disease, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    David M. Aronoff MD

  3. Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA

    Kevin G. Osteen

  4. VA Tennessee Valley Healthcare System, Nashville, TN, USA

    Kevin G. Osteen

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  1. Tianbing Ding PhD
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  2. Lauren A. Lambert
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  3. David M. Aronoff MD
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  5. Kaylon L. Bruner-Tran PhD
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Correspondence to Kaylon L. Bruner-Tran PhD.

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Ding, T., Lambert, L.A., Aronoff, D.M. et al. Sex-Dependent Influence of Developmental Toxicant Exposure on Group B Streptococcus-Mediated Preterm Birth in a Murine Model. Reprod. Sci. 25, 662–673 (2018). https://doi.org/10.1177/1933719117741378

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