The proposed 5-year project will allow us to identify the spectrum of bisphenol contaminants in our environment, gain insight to their metabolism during pregnancy, assess fetal exposure levels, and begin to assess effects of exposure on fetal development through studies of the fetal ovary. During the current project period, we have amassed a unique collection of human pregnancy specimens over a particularly interesting time in the history of bisphenol A (BPA) and other bisphenols. We have also improved analytical methodology for accurate and complete measurement of BPA and its metabolites and begun to extend this methodology to the analysis of emergent bisphenols that are replacing BPA. We propose to complete the development of new analytical tools and obtain data on parent and metabolite levels of replacement bisphenols in maternal (urine and serum) and fetal (cord serum and amniotic fluid) biospecimens from second trimester pregnancies. We will determine if BPA levels have changed with the appearance of new bisphenols, if the total `bisphenol load' is increasing with time in our study population, and assess current human fetal exposure levels. We also will conduct studies of metabolizing enzymes to evaluate maternal and fetal metabolism of bisphenols. Although exploratory in nature, these studies will allow us to test existing hypotheses about the key factors that influence fetal exposure and generate new hypotheses. Taken together, the unique and detailed information on maternal/fetal pairs that will be generated will allow us to analyze the impact of genetic variation on the metabolism of individual contaminants, and assess the effects of exposure on the earliest stages of egg development in the fetal ovary.
Rapid introduction of new chemicals with endocrine disrupting properties into consumer products provides an ever-changing list of potentially harmful contaminants in our daily lives. The proposed studies provide a rare opportunity to track the emergence over nearly a decade of one such class of chemicals, bisphenols. We will determine the frequency and levels of contamination for different bisphenols - including the premier member of this class of chemicals, bisphenol A - in biospecimens from second trimester maternal/fetal pairs to identify those of most concern and gain insight to their metabolism and effect on the developing fetus.
| Horan, Tegan S; Pulcastro, Hannah; Lawson, Crystal et al. (2018) Replacement Bisphenols Adversely Affect Mouse Gametogenesis with Consequences for Subsequent Generations. Curr Biol 28:2948-2954.e3 |
| Yang, Qi-En; Nagaoka, So I; Gwost, Ivy et al. (2015) Inactivation of Retinoblastoma Protein (Rb1) in the Oocyte: Evidence That Dysregulated Follicle Growth Drives Ovarian Teratoma Formation in Mice. PLoS Genet 11:e1005355 |
| Vrooman, Lisa A; Oatley, Jon M; Griswold, Jodi E et al. (2015) Estrogenic exposure alters the spermatogonial stem cells in the developing testis, permanently reducing crossover levels in the adult. PLoS Genet 11:e1004949 |
| Vrooman, Lisa A; Nagaoka, So I; Hassold, Terry J et al. (2014) Evidence for paternal age-related alterations in meiotic chromosome dynamics in the mouse. Genetics 196:385-96 |
