Brain inflammation caused by air pollution reduces sperm count in mice

Inflammation of certain neurons in the hypothalamus region of the brain is responsible for reduced sperm counts in male mice exposed to high-levels of air pollution, scientists have shown.

The link between air pollution and reduced fertility is not new. Human studies have associated exposure to high-levels of fine airborne particles of particulate matter less than 2.5 micrometres in diameter (PM2.5), with poor sperm quality in men (see Bionews 928), reduced egg reserves in women (see BioNews 1004), and increased risk of infertility in couples (see BioNews 1084). The new mouse study published in Environmental Health Perspectives, by scientists from the University of Maryland School of Medicine, however, is among the first to provide a potential mechanism explaining the link between air pollution and low sperm count and also a potential target for therapies to reduce this effect.

'Our findings showed that the damage due to air pollution – at least to the sperm count – could be remedied by removing a single inflammation marker in the brains of mice, suggesting that we may be able to develop therapies that could prevent or reverse the damaging effects of air pollution on fertility,' said study lead Dr Zhekang Ying.

Previous research had shown that although mice exposed to high levels of PM2.5 have low sperm counts, their testes do not show signs of inflammation. This observation prompted the scientists to look for alternative mechanisms behind this phenomenon. They speculated that inflammation of the brain caused by air pollutions could be responsible for changes in testicular function. Researchers bred mice to lack the pro-inflammatory enzyme inhibitor kappa B kinase 2 (IKK2) marker in their brain cell and exposed them to high concentrations of PM2.5. This reduced sperm counts in healthy mice but sperm counts remained normal in the mutant mice.

To narrow down the site of brain inflammation that leads to reduced sperm count, researchers then removed IKK2 in a specific group of neurons located in the hypothalamus, a brain structure which controls the production and release of several hormones into the blood stream. Removing the pro-inflammatory enzyme inhibitor from neurons of the hypothalamus known to be involved in the control of food intake and the sleep-wake cycle, resulted in mice with normal sperm counts despite exposure to PM2.5.

'Looking back, it makes perfect sense that the neurons in the hypothalamus are the culprits perpetuating this inflammation response that results in low sperm count, as we know that the hypothalamus is a major pathway link between the brain and the reproductive system,’ explained Dr Ying.

It is important to note the PM2.5 concentrations used in the study were higher than those experienced in most human habitats and the effects on sperm count reduction were relatively small.