Monophosphoryl lipid A alleviated radiation‐induced testicular injury through TLR4‐dependent exosomes

Abstract

Radiation protection on male testis is an important task for ionizing radiation‐related workers or people who receive radiotherapy for tumours near the testicle. In recent years, Toll‐like receptors (TLRs), especially TLR4, have been widely studied as a radiation protection target. In this study, we detected that a low‐toxicity TLR4 agonist monophosphoryl lipid A (MPLA) produced obvious radiation protection effects on mice testis. We found that MPLA effectively alleviated testis structure damage and cell apoptosis induced by ionizing radiation (IR). However, as the expression abundance differs a lot in distinct cells and tissues, MPLA seemed not to directly activate TLR4 singling pathway in mice testis. Here, we demonstrated a brand new mechanism for MPLA producing radiation protection effects on testis. We observed a significant activation of TLR4 pathway in macrophages after MPLA stimulation and identified significant changes in macrophage‐derived exosomes protein expression. We proved that after MPLA treatment, macrophage‐derived exosomes played an important role in testis radiation protection, and specially, G‐CSF and MIP‐2 in exosomes are the core molecules in this protection effect.

The hydrogen storage nanomaterial MgH 2 improves irradiation-induced male fertility impairment by suppressing oxidative stress

“…The indirect effect of dissociated water produced after IR exposure can lead to testis injury [ 24 ]. Oxidative stress is the result of an imbalance between the generation and consumption of excessive ROS and the decreased activity of the antioxidant defense system [ 25 ].…”

“…The irradiation-induced increase in ROS production is also related to the increase in apoptosis [ 39 ]. Mitochondria are an important organelle for the process of apoptosis, which is mainly triggered by the release of Cytochrome C from the mitochondria into the cytoplasm and is mainly mediated by Bcl2 family proteins [ 24 ]. Bax , an apoptosis-promoting factor, is located in the cytosol.…”

The Hydrogen Storage Nanomaterial MgH2 Improves Irradiation-induced Male Fertility Impairment by Suppressing Oxidative Stress

“…Mitochondria are an important organelle for the process of apoptosis, which is mainly triggered by the release of Cytochrome C from the mitochondria into the cytoplasm and is mainly mediated by Bcl2 family proteins [25]. Bax, an apoptosis-promoting factor, is located in the cytosol.…”

“…At present, an increasing number of free radical scavengers have been identi ed. On the other hand, the indirect effect of dissociated water produced after IR exposure can lead to testis injury [25]. Oxidative stress is the result of an imbalance between the generation and consumption of excessive ROS and the decreased activity of the antioxidant defense system [26].…”

Melatonin Ameliorates Inflammation and Oxidative Stress by Suppressing the p38MAPK Signaling Pathway in LPS-Induced Sheep Orchitis

“…Isolation of Leydig cells for culturing was preformed according to a procedure described in [ 20 ]. The co-culture experiment of testicular macrophages and Leydig cells has also been previously described [ 21 , 22 ]. In the co-culture system, testicular macrophages (0.4 × 10 5 /mL) were cultured in a transwell plate; Leydig cells (1.6 × 10 5 /mL) were cultured in the bottom of the plate (Corning Company, 3491, New York, NY, USA).…”