Augmentation Of SWP Expression Contributes To Hypergravity-induced Reproductive Injury In Male Mouse

Background and objectivesA major goal of space life sciences research is to broaden scientific knowledge of the influence of gravity on living systems. Investigators have known for decades that the spaceflight environment can have dramatic effects on reproductive system. However, there are only limited reports on the mechanisms behind these changes.The spaceflight environment includes at least three factors that likely influence reproduction. These include mission-related psychological stress, low-dose-to-low-dose rate radiation, and changes in inertial condition (i.e., microgravity and hypergravity).Mammalian reproduction evolved within Earth's 1-g gravitational field. Therefore, deviations from Earth's normal gravity, i.e., hypogravity (forces<1 g) or hypergravity (forces>1 g), may compromise reproduction. Lift-off and re-entry of the spacecraft are associated with exposure to increased gravity (hypergravity). However, limited spaceflight opportunities and confounding effects of various nongravitational factors associated with spaceflight (i.e., radiation, stress) have led to the development of ground-based models for studying the effects of altered gravity on biological systems. Centrifugation is used to study hypergravity.The present study was designed to investigate effects of hypergravity on reproduction of male mouse and the mechanisms behind it.Methods and results1. In the mice subjected to hypergravity (3.3G) in the centrifuge, the number or motility of sperm, testosterone concentration of serum and NO-production of testis was decreased and the apoptosis of testicular cells was increased significantly. But the body weight, testis weight and capture rate did not change significantly.2. A novel protein, swiprosin-1(SWP) was found highly expressed in testis after mice suffered hypergravity and the expression increased with the times and intensity of hypergravity. The SWP was found distributed in the leydig cells in testis with Immunohistochemistry analysis.3. The expression of SWP in mice testis has no significant decreased after three different kinds of stress, hypoxia, hot, and hypothermia. In the primary cultured leydig cells, neither dexamethasone nor corticosterone did change the expression of SWP.4. The number or motility of sperm decreased after swiprosin-1 RNAi and also decreased after SWP overproduction through direct injection of recombinant lentivirus into mouse testis.5. The apoptosis in cultured leydig cells was decreased in after SWP RNAi and increased after SWP over-expression according to the expression of caspase-3, bax and bcl-2.6. The concentration of NO of the supernatant of cultured leydig cells and expression of iNOS increased after SWP RNAi, decreased after SWP overproduction.7. The concentration of testosterone of the supernatant of cultured leddig cells decreased after SWP over-expression, increased after SWP RNAi.ConclusionAugmentation of SWP expression attributes to hypergravity-induced reproductive injury in mouse. The protein-SWP may be an important target for prevention or treatment for hypergravity-induced reproductive injury.