Prostate ‘organoids’ suggest how early bisphonel A exposure could increase cancer risk

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Researchers from the University of Illinois at Chicago (UIC) have cultured the world’s first prostate ‘organoid’ from human embryonic stem cells (hESCs). This model has been used to demonstrate that bisphenol A (BPA) can cause overproduction of prostate stem cells, possibly increasing a man’s risk of developing prostate cancer.

BPA is an additive used to soften plastic and found in everything from water bottles to carbonless receipts: it is a known endocrine disruptor that mimics oestrogen. Previous studies using rodent and adult human prostate stem-progenitor cell models suggest that early exposure to BPA can predispose to an individual to developing cancerous prostate cells later in life. However, prior to this study, published in PLOS ONE, it was unknown whether embryonic human prostate was equally susceptible to BPA during its natural developmental window.

To address this unmet need, the team pioneered the creation of prostate ‘organoids’. Only a couple of millimetres in size, these cells were cultivated from hESCs with precise control of growth factor and steroids, enabling researchers to investigate the effects of BPA exposure at different stages of differentiation, mimicking the effects of this exposure in utero.

A normal prostate gland has just a few stem cells dispersed throughout, which give rise to new prostate tissue over the course of a man’s life. This study found that BPA exposure caused the organoid to grow an overabundance of prostate stem cells in ‘nests’ throughout the tissue. It is thought, this overproduction could result in increased sensitivity to the naturally rising levels of oestrogen produced as a man ages, driving prostate cancer risk.

“The higher number of stem cells we saw in developing organoids given very low doses of BPA may be the underlying mechanism by which BPA increases the risk for prostate cancer,” commented lead author, Gail Prins, Professor of Physiology in the UIC College of Medicine and director of UIC’s Andrology laboratory. “Stem cells divide infrequently, but they may last a lifetime, carrying forward any abnormalities to all the tissues they give rise to. In theory, the more stem cells an organ has, the greater the risk of mutations that could cause the tissue to turn cancerous.”

This study supports Prin and team’s aforementioned research and provides the first direct evidence that low-dose BPA exposure targets hESC and causes structural changes to cell development as the embryonic cells differentiate towards human prostate organoids, suggesting that the developing human prostate may be susceptible to disruption by BPA exposures.

Prins continues, “This is as definitive as it gets, when it comes to the effect of BPA on the developing prostate. It produces an abnormally high number of prostate stem cells in the tissue, and these nests are a strong candidate for why exposure to BPA during development has been linked to prostate cancer later in life.”

Sources: Prostate ‘organoid’ hints at how early BPA exposure may increase cancer risk. Sharon Parment; Directed Differentiation of Human Embryonic Stem Cells into Prostate Organoids In Vitro and its Perturbation by Low-Dose Bisphenol A Exposure. PLOS ONE. Calderon-Gierszal and Prins. doi: 10.1371/journal.pone.0133238