Researchers have offered promising insights into the effects of antimicrobial peptide MPX in addressing oxidative stress and maintaining blood-testis barrier integrity, key factors in male infertility exacerbated by testicular inflammation.
Published in the journal Scientific Reports on March 19, 2025, the study delves into the significance of MPX as an innovative strategy against the detrimental impacts caused by lipopolysaccharide (LPS), a component of gram-negative bacteria that can induce severe inflammation and oxidative stress in the testes. The research team, including authors Zhu et al., explored how orally administered antimicrobial peptides can mitigate oxidative stress while repairing the blood-testis barrier, which plays an essential role in spermatogenesis—the process of sperm development.
The study evaluated the effects of administering 0.5 mg/kg MPX to male Kunming mice over 20 and 40 days. By dividing the subjects into six groups—including controls and those receiving LPS—the researchers were able to measure vital parameters such as glutathione (GSH), total superoxide dismutase (T-SOD), catalase (CAT), nitric oxide (NO), malondialdehyde (MDA), and lactate dehydrogenase (LDH) in both serum and testicular tissues.
Results showed a significant increase in testicular GSH, T-SOD, and CAT levels in MPX-treated mice across both intervals. Moreover, there was a marked reduction in oxidative stress markers MDA and LDH, indicating that MPX is effective in counteracting the harmful effects of LPS.
In further analysis, MPX not only improved oxidative stress parameters but also upregulated the expression of crucial proteins associated with cellular defense against oxidative stress, such as Kelch-like ECH-associated protein 1 (Keap1), Nuclear factor erythroid 2-related factor 2 (Nrf2), and Glutamate cysteine ligase, modifier (GLCM), while downregulating Glutamate cysteine ligase, catalytic (GCLC) and Inducible nitric oxide synthase (iNOS)—glycoproteins that can exacerbate inflammatory responses.
Additionally, the research indicated that MPX administration promoted a substantial increase in sperm count and motility, along with repairing the LPS-induced damage to the blood-testis barrier, through the upregulation of tight junction proteins including Claudin, Occludin, N-cadherin, and E-cadherin, which are essential for maintaining the barrier’s integrity. “This study systematically evaluated the long-term effects of the orally administered antimicrobial peptide MPX on oxidative stress and the blood-testis barrier in the male reproductive system,” wrote the authors of the article.
Key insights from the pharmacokinetic analysis indicated that FLTC-MPX was first distributed in the stomach, later showing multi-tissue distribution, with fluorescence signals detectable in testicular tissue after just one hour following administration. This not only substantiates the testicular targeting potential of MPX but also showcases its therapeutic promise in treating testicular inflammatory diseases.
The researchers conclude that given the growing evidence of MPX’s efficacy in counteracting oxidative stress and preserving blood-testis barrier function, this antimicrobial peptide might serve as a viable treatment pathway for male infertility related to testicular inflammation. Their findings highlight the functional advantages of MPX in the prevention and treatment of conditions such as orchitis, further underlining the importance of seeking novel therapies in the field of reproductive health.
