The role of iron in the course of bacterial infection of the testis

• Applicant: Professor Dr. Andreas Meinhardt
• Subject Area: Reproductive Medicine, Urology
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 424111918

A major cause for environmentally induced male infertility is related to acute infectious epididymo-orchitis elicited by bacteria such as Neisseria gonorrhoeae, Chlamydia trachomatis or the uropathogenic E. coli (UPEC). Following UPEC infection, a reduction of epididymal sperm counts was observed also long after the resolution of the infection, which suggests a testicular involvement and possible damage to germ cells. UPEC has an exceptionally large range of iron acquisition systems which enable it to survive in extremely iron poor environments. In collaborative preparatory work, we have demonstrated that iron trafficking proteins are polarized in Sertoli cells and may participate in an internal iron cycle, which provides a constant controlled supply of iron to early developing germ cells to protect the developing sperm from oxidative stress and peripheral iron as well as nutrient fluctuations in general. We thus hypothesize, that UPEC infection will perturb the testicular iron homeostasis through UPEC elicited manipulation of host-iron regulatory proteins, directly affecting the host iron homeostasis and that the UPEC-elicited shift in iron homeostasis in the testis contributes to the course of the infection and male fertility. To test this hypothesis, the Meinhardt and Meyron-Holtz labs, experts in immunology of the male reproductive tract and iron metabolism, respectively, have teamed up. We will use an established mouse-model for UPEC mediated epididymo-orchitis to test how the infection with hemolysin A (hemolysin A is a pore forming protein important for iron acquisition of UPEC) positive or hemolysin A negative UPEC-strains will affect iron homeostasis, the course of the infection and fertility parameters in these mice. Understanding the contribution of iron homeostasis to male fertility during UPEC infection may lead to novel treatment strategies and the improvement of male fertility, following UPEC infection.

• DFG Programme: Research Grants
• International Connection: Israel
• International Co-Applicant: Privatdozentin Esther Meyron-Holtz, Ph.D.