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Objective: Progesterone receptor is present in human sperm. Here, we determined if progesterone (P4) improves capacitation and stimulates sperm survival by suppressing apoptosis to evaluate its relevance to be used as a preservation agent to increase and prolong sperm viability and motility. Materials and Methods: Semen samples were obtained from healthy human donors. The sample was washed by Percoll gradient centrifugation and was divided into five groups of 500 µL, each containing approximately 10 million sperm cells. P4 was added to each group at the final concentrations of 0 (control), 250, 500, 750, and 1000 ng/mL, respectively, and was incubated at 37°C for 2 h. Sperm motility was assessed using a computer-assisted sperm analyzer. Tyrosine phosphorylation, Akt phosphorylation, and caspase-3 activation in sperm were analyzed by western immunoblotting. Results: P4 did not increase the sperm motility. Western blot analysis revealed that P4 at the concentration of 500 ng/mL increased tyrosine phosphorylation, indicating increased sperm capacitation. P4 at 750 mg/ml also increased Akt phosphorylation. Interestingly, the activation of Akt was associated with a decrease in caspase-3 activity, indicating the prosurvival effect of P4. Conclusion: This study results suggest that P4 does not influence sperm motility; however, it increases sperm tyrosine phosphorylation (at a specific concentration of 500 ng/ul), activates AKT (Protein kinase B), and suppresses caspase-3 (at a specific concentration of 750 ng/ul). The biochemical effects of P4 on sperm may warrant its use as a preservation agent to increase sperm viability. [ABSTRACT FROM AUTHOR]