Stress, plastics and male infertility

“Modern life is having a devastating impact on men's fertility,” reported the Daily Mail . The newspaper looked at research claiming to show that the combination of stress and a “gender-bending” chemical found in plastics raises the odds of reproductive defects and undescended testicles.

The animal research has offered one explanation for the rising number of babies born with these conditions. However, it involved exposing rats to chemicals at levels that humans are usually not exposed to. This means the conclusions should be treated with caution.

As this study was mainly about the effect of high doses of a chemical called phthalates on the number of rats born with undescended testicles, it is premature to report that stress has a part to play in reducing fertility in men.

Where did the story come from?

This research was carried out by Dr Amanda Drake and colleagues from the Centres for Cardiovascular Science and Reproductive Biology at the Queen’s Medical Research Institute, University of Edinburgh. The study was supported by a European Union and Medical Research Council grant. It was published in the peer-reviewed medical journal Endocrinology .

What kind of scientific study was this?

In this animal study, the researchers looked at how conditions in the womb affected the development of male rats.

They begin by describing the importance of their research to humans in terms of male reproductive abnormalities. They say undescended testicles (cryptorchidism), misaligned urinary tracts (hypospadias) and low sperm counts are common. They link the three conditions to a syndrome called testicular dysgenesis syndrome (TDS), saying this is the result of reduced androgen production or action during a critical period of intrauterine development.

The researchers suggest that a recent increase in the occurrence of  this syndrome suggests that environmental or lifestyle factors could be a cause. They say the increase is “not replicated in all reports”.

In rats, the critical time for the development of the male reproductive tract is around day 15 to 17 of embryo development (equivalent to eight to 14 weeks’ gestation in humans). Having a deficiency of androgens (testosterone-like hormones) at this time have been shown to lead to the syndrome.
The researchers gave some pregnant rats chemicals called phthalates, which are solvents used to soften plastic. They can be found in household goods like shower curtains, vinyl floors, plastic packaging, toys and credit cards.

The rats were separated into six groups. Two groups were given daily doses of a phthalate ester called dibutyl phthalate (DBP), either 100mg/kg or 500 mg/kg. Three groups were given injections of a stress hormone, called dexamethasone, either alone or in combinations with the two doses of DPB. A sixth group was given an inert injection as a control treatment.

The researchers measured birth weight and made other general observations such as the distance between the anus and genitals in the animals (AGD), penis length, testicular weights and the blood testosterone levels in adulthood. The number and severity of any hypospadias were recorded, as well as any cases of undescended testicles.

What were the results of the study?

Looking at the results across the six combinations of treatments, the researchers found:

• Out of 40 animals treated with the control injections, none developed cryptorchidism (undescended testicles) and none developed hypospadias (misaligned urinary tracts).
• Out of 35 animals treated with dexamethasone, 3% developed cryptorchidism and none developed hypospadias.
• Out of 45 animals treated with a low dose DBP, none developed cryptorchidism or hypospadias.
• Out of 32 animals treated with high dose DBP, 53% developed cryptorchidism and 31% developed  hypospadias.
• Out of 33 animals treated with dexamethasone and low dose DPB, 3% developed cryptorchidism and none developed hypospadias.
• Out of 33 animals treated with dexamethasone and high dose DPB, 86% developed cryptorchidism and 45% developed hypospadias.

The researchers say the stress hormone alone did not affect the development of the baby rats' testicles or urinary systems, but the phthalate did. Giving the two together magnified the problems.

What interpretations did the researchers draw from these results?

The researchers cautiously acknowledge that although these animal studies are useful to show the mechanisms by which early life exposures can cause later disease, large doses of phthalate were required to cause this effect. They say that in terms of phthalate exposure in humans, “It is unclear whether the human foetus is exposed to sufficient levels of such chemicals to result in any adverse effect.”

What does the NHS Knowledge Service make of this study?

There are inconsistencies between what these researchers report in this animal study (and some of the implications they draw for human health) and what is reported in the newspapers. For example:

• The researchers say their observations support the concept of testicular dysgenesis syndrome (TDS) and that they have shown that combinations of lifestyle and environmental exposures during a critical developmental period may be of crucial importance in determining the risk of TDS disorders.  However, they did not test for lifestyle factors and used one dose of a synthetic injected hormone as a model for “stress”.
• This study did not look at fertility rates in the rats. The implication is that the changes in testosterone levels observed are somehow linked to fertility in the animals, but any link has not been demonstrated.
• As this study was mainly about high dose phthalates and undescended testicles, and the stress hormone, dexamethasone, had a tiny effect in comparison, to report that stress has a part to play in male fertility in humans.

The animal research has offered an explanation for the rising number of babies born with these conditions. However, the research is based on a level of exposure to chemicals that humans usually do not have. As such, the conclusions should be treated with caution. Further research is needed into this and the many other environmental and lifestyle factors that are competing for attention in this field of research.