Researchers identify new cause of male infertility in human studies.

Involuntary childlessness is common, and in half of all cases attributable to infertility in the man. Although male infertility has many possible causes, it often remains unexplained.  Now, a new study from Karolinska Institutet finds a new cause of male infertility by linking this condition to autoimmune prostatic inflammation.

Previous studies show that infertility is common in people of both sexes with the disease. While infertility in women with APS1 is caused by autoimmune action against the ovaries, what gives rise to the corresponding infertility in men has never been ascertained. Keen to investigate whether male fertility could be explained by an autoimmune reaction against some part of the male reproductive organs, the new study examined the immune system of 93 men and women with APS1.

In the current study, the researchers discovered a reason for reduced fertility in people with autoimmune polyendocrine syndrome type 1 (APS1), which increases the risk of developing autoimmune disease (caused by the immune system attacking and damaging healthy cells) and which is often used as a model for autoimmune disease in general.

The data findings showed that the immune system in a large group of patients reacted to a protein formed only in the prostate, namely the enzyme transglutaminase 4. The results also showed that it was only men who reacted to transglutaminase 4 and that the immune reaction first appeared at the onset of puberty once the prostate gland had matured. Interestingly, previous animal models have shown that transglutaminase 4 plays an important part in male fertility.

To better understand the data findings, the team examined the animal model for APS1 where the mice have the same genetic defect as human patients with the syndrome.  The data findings showed that male mice spontaneously developed an inflammatory disease in their prostate glands, a so-called prostatitis, and reacted to transglutaminase 4.

The team surmise that the study is important as it points to a new disease mechanism for male infertility.   However, they stress that more work needs to be done to understand the significance of autoimmune prostatitis to infertility in the male population at large.

Source:  Karolinska Institutet