Project 2: Endocrine Disrupting Chemicals,
Diet and Gonadal Toxicity

Learn More

 

Significant Results

 

  • Embryonic BPA exposure in mice increased the percentage of germ cells remaining in germ cell nests compared to control mice (see figure), and also decreased the percentage of formed primordial follicles compared to controls.   Female fertility depends on breakdown of the germ cell nests and development of an adequate number of healthy primordial ovarian follicles, thus, disrupted regulation of primordial follicle numbers can reduce female fertility. 

 

  • Embryonic BPA exposure increased the expression of anti-apoptotic factors (i.e. factors that prevent cell death) and decreased expression of pro-apoptotic factors (factors that promote cell death) in the ovaries of exposed mice.  Together these changes could be the underlying mechanism by which BPA increased the percentage of germ cells remaining in germ cell nests and decreased the percentage of formed primordial follicles. 

 

  • Embryonic BPA exposure adversely affected estrous cyclicity and reproductive success especially as animals aged.

 

 

 

 

 

Publications

Zhou, C., Flaws, J.A. (2017) Effects of an environmentally relevant phthalate mixture on cultured mouse antral follicles. Toxicological Sciences (in press). https://academic.oup.com/toxsci/article-lookup/doi/10.1093/toxsci/kfw245

 

Barakat, R., Lin, P-C., Rattan, S., Brehm, E.S., Canisso, I.F., Abosalum, M.E., Flaws, J.A., Hess, R., Ko, C. (2017) Prenatal exposure to DEHP induces premature reproductive senescence in male mice. Toxicological Sciences (in press).https://academic.oup.com/toxsci/article-lookup/doi/10.1093/toxsci/kfw248

 

Zhou, C., Gao, L., Flaws, J.A. (2017) Prenatal exposure to an environmentally relevant phthalate mixture disrupts reproduction in F1 female mice. Toxicology Applied Pharmacology 318:49-57. http://www.sciencedirect.com/science/article/pii/S0041008X17300303

 

Zhou, C., Gao, L., Flaws, J.A. (2017) Exposure to an environmentally relevant phthalate mixture causes transgenerational effects on female reproduction in mice. Endocrinology (in press). https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2017-00100

 

Gal A, Lin PC, Barger AM, Macneill AL, Ko C.  (2014) Vaginal fold histology reduces the variability introduced by vaginal exfoliative cytology in the classification of mouse estrous cycle stages.  Toxicologic Pathology (Epub ahead of print). http://tpx.sagepub.com/content/early/2014/04/25/0192623314526321.long

 

Peretz, J., Vrooman, L., Ricke, W.A., Hunt, P.A., Ehrlich, S., Hauser, R., Padmanabhan, V., Taylor, H., Swan, S.H., VandeVoort, C., Flaws, J.A.  (2014) Bisphenol A and Reproductive Health: Update of Experimental and Human Evidence.  Environmental Health Perspectives (Epub ahead of print). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123031/

 

Peretz, J., Vrooman, L., Ricke, W.A., Hunt, P.A., Ehrlich, S., Hauser, R., Padmanabhan, V., Taylor, H., Swan, S.H., VandeVoort, C., Flaws, J.A.  (2014) Bisphenol A and Reproductive Health: Update of Experimental and Human Evidence.  Environmental Health Perspectives (Epub ahead of print). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123031/

 

Wang W., Hafner K., Flaws J.A. (2014) In utero bisphenol A exposure disrupts germ cell nest breakdown and reduces fertility with age in the mouse.  Toxicology and Applied Pharmacology 276:157-64. http://www.sciencedirect.com/science/article/pii/S0041008X14000465

 

R. N. Sadowski, L.M. Wise, P. Y. Park, S. L. Schantz, and J. M. Juraska  Early exposure to bisphenol A alters neuron and glia number in the rat prefrontal cortex of adult males, but not females.  Submitted to Neuroscience. http://www.sciencedirect.com/science/article/pii/S0306452214007155

 

Sadowski R.N., P. Park, S.L.Neese, D.C. Ferguson, S.L. Schantz and J.M. Juraska  Effects of perinatal bisphenol A exposure during early development on radial arm maze behavior in adult male and female rats.  Neurotoxicol Teratol, 42: 17-24, 2014, PMID: 24440629. http://www.sciencedirect.com/science/article/pii/S089203621400004X

 

Peretz, J., Vrooman, L., Ricke, W.A., Hunt, P.A., Ehrlich, S., Hauser, R., Padmanabhan, V., Taylor, H., Swan, S.H., VandeVoort, C., Flaws, J.A.  (2014) Bisphenol A and Reproductive Health: Update of Experimental and Human Evidence.  Environmental Health Perspectives (in press). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123031/

 

Peretz, J., Flaws, J.A.  (2013) Bisphenol A down-regulates rate-limiting Cyp11a1 to acutely inhibit steroidogenesis in cultured mouse antral follicles.  Toxicology Applied Pharmacology 27:249-56. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742584/

 

Brannick, K.E., Craig, Z.R., Himes, A.D., Peretz, J.R., Wang, W., Flaws, J.A., Raetzman, L.T.  (2012) Prenatal exposure to low doses of bisphenol A affects pituitary gonadotropes in a sex and dose dependent manner. Biology of Reproduction 87:82. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507543/

 

Peretz, J., Craig, Z.R., Flaws, J.A.  (2012)  Bisphenol A inhibits follicle growth and induces atresia in cultured mouse antral follicles independently of the genomic estrogenic pathway.  Biology of Reproduction 87:63. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464906/

 

Peretz, J., Gupta, R.K., Singh, J., Hernandez-Ochoa, I., Flaws, J.A.  (2011)  Bisphenol A impairs follicle growth, inhibits steroidogenesis, and down-regulates rate-limiting enzymes in the estradiol biosynthesis pathway.  Toxicological Sciences 119:209-217. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003833/