A new finding made by scientists at the University of Marseille may be key to understanding certain types of male infertility and, more importantly, finding an effective treatment for them. The research, published in the Journal of Experimental Medicine , has described the origin, development and characteristics of immune cells that “defend” sperm. A kind of “guardians of fertility”, which prevent other agents of the immune system from entering the testicles.
Specifically, a type of cell has been analyzed: testicular macrophages. These not only migrate to the sites of infection and pathogens, but also modulate the activity of the immune system to ensure proper organ function and regeneration . Research with mice has made it possible to describe testicular macrophage populations in depth.
From the beginning of life, an individual’s immune system learns to distinguish the “self”, that is, native cells, from other potentially pathogenic cells. But in men, since sperm does not appear until puberty, it can be mistaken for foreign cells by certain elements of the immune system. Testicular macrophages are special immune cells that have a defense function for sperm. By releasing specific molecules, they prevent other agents of the immune system from entering the testes.
The testicle is divided into two compartments . One type of testicular macrophage is found in the interstitial spaces, where testosterone-producing cells are also located. These interstitial macrophages are of embryonic origin : they are present from the beginning of the individual’s life. The other type is located in the area where sperm (seminiferous tubules) form and mature. Each macrophage population has distinctive cellular markers . Macrophages can arise from embryonic progenitors or bone marrow cells in adults.
Image: cross section of the testicle of the newborn mouse, where we can see the seminiferous tubules in red, surrounded by testicular macrophages, in green. / Noushine Mossadegh-Keller and Sébastien Mailfert.
The researchers, led by Michael Sieweke of the Luminy Center for Immunology in Marseille, used a new method of cell tracking to follow the movement of macrophages from the bone marrow to the testes. They found that these macrophages appear only two weeks after the mice are born, which corresponds to the pubescent stage in human males. Surprisingly, once they have established themselves in the testes, macrophages from both populations remain there for the rest of their lives.
Testicular macrophages are the main immune cells of the mammalian testes. Beyond the classic immune functions, they have been shown to be important for the manufacture of sperm and the production of male hormones. Although the study has identified two different macrophage populations in the adult testis based on their location and different tissue morphology, their evolutionary origin and mode of maintenance are still unknown.
Sieweke’s team will now focus their research efforts on the relationships between macrophages, sperm, and testosterone production, which may lead to innovative treatments for certain types of male infertility.
References:
Developmental origin and maintenance of distinct testicular macrophage populations. Noushin Mossadegh-Keller, Rebecca Gentek, Gregory Gimenez, Sylvain Bigot, Sebastien Mailfert, Michael H. Sieweke. DOI: 10.1084 / jem.20170829
