By Rachael Rogers, PhD Candidate in Reproductive Biology, and Professor Andrew Pask, Professor in Genetics, both at the University of Melbourne.

We all know that plastics are bad for the environment, but did you also know that they could be affecting our fertility and reproductive health too?

Infertility is a major issue in society today, with the World Health Organisation stating that one in six people will experience infertility in their lifetime.¹ On top of this, we have also seen a dramatic decrease in both male sperm count and female conception rates by almost 50% in the past 50 years.^2,3 This decrease in fertility can be largely attributed to our increasing exposure to chemicals in our environment known as endocrine disrupting chemicals (EDCs).

EDCs are defined as any agent that can block or interfere with the natural hormones within our body, like oestrogen and testosterone. Hormones are essential for our reproductive health and development, and any disruption to normal hormonal signalling can impact our fertility and increase our risk of developing reproductive disorders. EDCs are ubiquitous in our environment; they’re present in herbicides, pesticides, cosmetics, and pharmaceuticals, however, they’re most commonly found in plastics.

Plastics are made of plasticisers, and these plasticisers are often EDCs. Two of the most common plasticisers are BPA and phthalates. BPA is an estrogenic EDC, meaning it can bind to and activate the oestrogen receptor, thereby leading to unwanted oestrogen signalling. BPA is added to a variety of products including food and drink containers, baby bottles, plastic wrap and it is even used in the lining of receipts. Under certain conditions, such as heat and UV, BPA can leach from these products leading to high human exposure. BPA is so ubiquitous in our environment that studies have shown that 92% of the US population have detectable levels of BPA present in their urine.⁴ This is alarming as BPA is a known reproductive toxicant.

An Italian study investigating the effects of EDCs on female reproductive health found that women experiencing infertility have significantly higher levels of BPA present in their blood compared to fertile women.⁵ BPA exposure has also been associated with polycystic ovary syndrome (PCOS), one of the most common female reproductive disorders affecting 5-15% of women.⁶ Women with PCOS have been shown to have significantly higher levels of BPA in their blood compared to women without PCOS.⁷ Animal studies have also highlighted the negative reproductive effects of BPA, with prenatal exposure significantly impacting the timing of puberty and reducing fertility in female mice.⁸

The other common class of plasticisers are phthalates, with the most ubiquitous being diethylhexyl phthalate (DEHP). DEHP is commonly added to soft plastics to increase their flexibility, and, like BPA, is added to food and drink containers, as well as medical tubing and equipment (such as IV bags). This is an issue for premature babies, who are often connected to medical tubing for monitoring and support, as they can have exposures as high as 100 times the recommended upper limit of DEHP.⁹ DEHP exposure impacts both male and female reproduction, with accelerated puberty and impaired sperm motility (movement) having been observed in mice.^10,11

Although exposure to EDCs is harmful during all stages of life, it is particularly harmful during key developmental stages, such as pre- and neo- natal life. Activation or inhibition of normal hormonal pathways as the reproductive system develops can predispose individuals to disease later in life. Key genetic and epigenetic programming also occurs at this time, setting up germ cells (which go on to form the sperm and eggs) for the next generation. Any alterations to gene expression caused by EDC exposure, can hence not only contribute to reproductive diseases within a person, but also cause changes to their germ cells, impacting future generations.

Our research group at the University of Melbourne investigates the effects of EDCs on reproductive development. The specific EDC we research is called diethylstilbestrol (DES), a synthetic oestrogen drug that was prescribed to pregnant women between 1940-1970 in the hopes of preventing miscarriage and premature labour. Although DES is not found in plastics, we use it as a model to understand the impacts of other estrogenic EDCs present in the environment.

Our research found that exposing a pregnant mouse with DES doesn’t just affect the fertility in her offspring – reduced fertility continues to impact her descendants into the second and third generation in both males and females. This is alarming as the second and third generation developed in a normal hormonal environment and did not have a direct foetal exposure to DES. We also saw that the female descendants went through puberty significantly earlier than control females, and male descendants had significantly increased rates of hypospadias, a misplacement of the urethral opening on the penis. Hypospadias is the most common human congenital birth defect and its incidence has doubled in the past 50 years, now impacting 1 in every 125 live male births.¹² These results highlight the long-lasting effects of EDCs and suggest that what we are exposed to today may not only affect ourselves, but future generations to come.

Avoiding plastics and exposure to EDCs is almost impossible today, and a radical change to the way plastics are used is needed. Change can come about through consumer choice, such as choosing food and water which comes in metal or glass packaging over those made of plastic. Knowing which products to avoid and choosing those that don’t use EDC plastics can help, but this is hard due to the prevalence of these products in almost everything we use. Ultimately, we need more studies defining the impacts of EDCs on reproductive health to underpin global reform and stringent policies on the use of these chemicals in our environment.

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Rachael Rogers is a PhD Candidate in Reproductive Biology, working under the supervision of Professor Andrew Pask (Professor in Genetics) at the University of Melbourne.

This piece appears in the August 2023 edition of Science Victoria magazine. All issues can be read online for free at rsv.org.au/Science-Victoria.

References:

1. Infertility. (n.d.). Retrieved September 8, 2022, from who.int/health-topics/infertility
2. Levine, H., et al. (2017). Temporal trends in sperm count: A systematic review and meta-regression analysis. Hum Reprod Update, 23(6), 646–659. doi.org/10.1093/humupd/dmx022
3. Hamilton, B. E., & Ventura, S. J. (2006). Fertility and abortion rates in the United States, 1960-2002. Int J Androl, 29(1), 34–45. doi.org/10.1111/j.1365-2605.2005.00638.x
4. Calafat, A. M., et al. (2008). Exposure of the U.S. Population to Bisphenol A and 4-tertiary-Octylphenol: 2003–2004. Environmental Health Perspectives, 116(1), 39–44. doi.org/10.1289/ehp.10753
5. Caserta, D., et al. (2013). The influence of endocrine disruptors in a selected population of infertile women. Gynecological Endocrinology, 29(5), 444–447. doi.org/10.3109/09513590.2012.758702
6. Rasquin Leon, L. I., Anastasopoulou, C., & Mayrin, J. V. (2022). Polycystic Ovarian Disease. In StatPearls. StatPearls Publishing. hncbi.nlm.nih.gov/books/NBK459251/
7. Kandaraki, E., et al. (2011). Endocrine disruptors and polycystic ovary syndrome (PCOS): Elevated serum levels of bisphenol A in women with PCOS. J Clin Endocrinol Metab, 96(3), E480-4. doi.org/10.1210/jc.2010-1658
8. Ziv-Gal, A., et al. (2015). The effects of in utero bisphenol A exposure on reproductive capacity in several generations of mice. Toxicology and Applied Pharmacology, 284(3), 354–362. doi.org/10.1016/j.taap.2015.03.003
9. Koch, H. M., Preuss, R., & Angerer, J. (2006). Di(2-ethylhexyl)phthalate (DEHP): Human metabolism and internal exposure – an update and latest results1. International Journal of Andrology, 29(1), 155–165. doi.org/10.1111/j.1365-2605.2005.00607.x
10. Rattan, S., et al. (2018). Di(2-Ethylhexyl) Phthalate Exposure During Prenatal Development Causes Adverse Transgenerational Effects on Female Fertility in Mice. Toxicol Sci, 163(2), 420–429. doi.org/10.1093/toxsci/kfy042
11. Khasin, L. G., et al. (2020). The Impact of Di-2-Ethylhexyl Phthalate on Sperm Fertility. Frontiers in Cell and Developmental Biology, 8, 426. doi.org/10.3389/fcell.2020.00426
12. Nassar, N., Bower, C., & Barker, A. (2007). Increasing prevalence of hypospadias in Western Australia, 1980–2000. Archives of Disease in Childhood, 92(7), 580–584. doi.org/10.1136/adc.2006.112862