Prenatal Bisphenol A Exposure Alters Epithelial Cell Composition in the Rhesus Macaque Fetal Oviduct

Abstract

Bisphenol A (BPA) is an endocrine disrupting compound that is a pervasive environmental contaminant. Although it has been reported to affect the development of a variety of fetal reproductive tissues, data on the effect of fetal BPA exposure on oviducts were extremely limited and were only available in mice. To determine if there are adverse effects of gestational BPA exposure on fetal oviduct, we exposed pregnant rhesus macaques with female fetuses to oral or nonoral BPA during the last trimester of gestation (day 100 to term). After the treatment, fetal oviducts were collected for morphology evaluation. BPA exposure altered the percentages of different cell types (ciliated, nonciliated, and secretory) in the fetal oviduct and resulted in a significant high ciliated cell population in the BPA-exposed fetal oviduct. The distribution of ciliated cells on the epithelium in the BPA-exposed fetal oviduct was also altered. Gestational BPA exposure reduced the expression of mucosubstance and uteroglobin in secretory cells in the fetal oviduct. A comparison of the outcome of the fetal oviduct studies with similar outcomes previously reported in the lung from the same fetuses demonstrates that BPA exhibits opposite effects in these two organs. In conclusion, the BPA-associated alterations in the fetal oviduct could potentially affect the oviduct morphology and function later in life with a negative impact on fertility. The mechanisms of action of the differential response in the oviduct and the lung to BPA exposure require further investigation.

The Association of Ovarian Reserve with Exposure to Bisphenol A and Phthalate in Reproductive-aged Women

“… 23 24 25 BPA is likely to alter oviduct morphology and gene expression, affect implantation, and uterine morphology and function. 26 27 It is further hypothesized that BPA may affect estrous cyclicity and the expression of major determinants in the hypothalamic-pituitary axis, including kisspeptin and GnRH. Importantly, BPA has been regarded as an ovarian toxicant likely to act through multiple pathways including apoptosis, oxidative stress and folliculogenesis.…”

Toxicoepigenetics and Environmental Health: Challenges and Opportunities

“…Moreover, there is significant epigenetic heterogeneity within a given tissue and even within individual cell types. − Recent work demonstrated that estimates of epigenetic age or correlations between DNA methylation and environmental exposures vary widely within the same individual, depending upon the sample type investigated . Likewise, environmental exposures may alter the relative proportions of cell types in a given tissue, , making it difficult to distinguish between epigenetic programming at the cellular level from shifts in cell type. TE biomarker research poses some unique challenges due to the need for refined TE detection and DNA methylation analysis, especially since nonconserved CpGs in multiple copies of TEs may confound the true DNA methylation status .…”

The role of environmental exposures and the epigenome in health and disease

“…Thus, assessment of tissue-specific effects of environmental exposures may be masked by such heterogeneity. Moreover, environmental exposures may induce changes in the cellular composition of tissues (Trevino and Katz 2018;Hung et al 2019), complicating the interpretation of epigenetic studies. These challenges may be addressed through emerging methods in single cell analyses (Cheow et al 2016).…”