Morphofunctional state of the testicles and proinflammatory cytokines in experimental toxic injury condition
Introduction. It is known cytokines play an important role in the communication between different systems of the body, regulate embryogenesis and regeneration of cells. It is proved a number of cytokines involved in the process of regulation of the reproductive system.
The aim of our research was to study the dynamic changes of inflammatory cytokines in mice males under the influence of doxorubomicyne hydrochloride (DH).
Materials and methods. The study was conducted in adult male mice ICR. Toxic testicular affection was modeled by intraperitoneal introduction of DH, twice with an interval of 7 days. Pathomorphological study of testes and measurement of cytokines content (interleukin-2, interleukin-4, interleukin-6 and interleukin-13) by enzyme immunoassay (ELISA), were conducted. The withdrawal of animals from the experiment took place at the 1st, 7th, 28th and 35th days of the experiment.
Results. In the animals of the control group the distribution of the cells of spermatogenic epithelium due to the stages of maturation was observed: the layers of spermatogonia and spermatocytes, evently spaced Sertoli cells, the lumen of the convoluted seminiferous tubules filled with sperm. IL-2 content was 17, 44 pg/ml; IL-6 - 80.21 pg/ml.
On the first day of the experiment spermatogenic epithelium of the large number of convoluted tubules is somewhat disorganized, in the lumen formed spermatozoa are observed, the height of the epithelium is uneven, sometimes its detachment is found. The content of IL-2 decreased almost three times, at the same time the reduction of IL-6 is almost 20%.
On the 7th day of the experiment in the most convoluted tubules there is a violation of the organization of spermatogenic epithelium: the number of spermatogonia is prominantly reduced, intercellular spaces are widen, diameter of the tubules seems wider due to the lowering of the epithelium, tubular lumen filled by very single sperm, significantly reduced the number of Sertoli cells. The content of IL-2 remains the same, and IL-6 – is reduced as compared both to the control and previous period.
On the 28th day of the experiment number of spermatogonia is sharply reduced, significantly expanded intercellular spaces, most of the tubules is empty, in the lumen of tubules some rare sperm are found, Sertoli cell number is substantially reduced, interstitium is edematous. No significant increase in the content of IL-2 compared to the previous period, but compared to control its content remains below 44 %. This trend is also characteristic of IL-6 content – it’s 12,4 % increased compared to the previous period, but remains 13, 6 % below the control group data.
On the 35th day of the experiment convoluted tubules remain dilated and filled by protein detritus, dramatically reduced the number of spermatogonia, sperm is almost absent, basement membrane is thickened, hyperchromic, in many cases spermatogenic epithelium turns peeled off. IL-2 content reaches only 66, 5% of control. The content of IL-6 is 11 % lower than the control group.
Immediately after the cessation of DH toxic exposure there is a sharp decline of IL-2 and IL-6, but on the 7th day of the experiment their content grows up and this growth continues throughout the observation period to the 35th day. Such fluctuations in the content of proinflammatory cytokines lead to an additional deviation of the metabolic processes in the affected organs.
Conclusions. The research demonstrates the importance of cytokine influence on the course of the pathological process in the testes of male mice under the toxic damage conditions. Substantial fluctuations in the content of proinflammatory cytokines during chronic experiment were found: first, there is a sharp decline, and then – a gradual increase of the concentration of these cytokines.