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Ritonavir Has Reproductive Toxicity Depending on Disrupting PI3K/PDK1/AKT Signaling Pathway

Eun-Ju Jung1, Jae-Hwan Jo2, Claudine Uwamahoro1

  • 1Department of Animal Science and Biotechnology, Kyungpook National University, Sangju 37224, Gyeongsangbuk-do, Republic of Korea.

Toxics
|January 22, 2024
PubMed

Insights

Ritonavir (RTV) suppresses sperm function and viability by disrupting the PI3K/PDK1/AKT pathway. This study highlights RTV

Area of Science:

  • Reproductive Biology
  • Biochemistry
  • Pharmacology

Background:

  • Ritonavir (RTV), an antiviral used in COVID-19 treatments, also exhibits anti-cancer properties by inhibiting AKT signaling.
  • RTV can cause cytotoxicity and impair sperm function by altering AKT activity.
  • The specific mechanisms by which RTV affects AKT signaling in spermatozoa are not well understood.

Purpose of the Study:

  • To investigate the male reproductive toxicity of Ritonavir (RTV) in spermatozoa.
  • To elucidate the effects of RTV on the phosphoinositide 3-kinase/phosphoinositide-dependent protein kinase-1/protein kinase B (PI3K/PDK1/AKT) signaling pathway in sperm.

Main Methods:

  • Duroc spermatozoa were exposed to varying concentrations of RTV.
  • Sperm capacitation was induced.
  • Sperm functions (motility, kinematics, viability, capacitation, acrosome reaction) and protein expression (tyrosine phosphorylation, PI3K/PDK1/AKT pathway) were assessed.

Main Results:

  • RTV significantly reduced sperm motility, motion kinematics, capacitation, acrosome reaction rates, and cell viability.
  • RTV increased phospho-tyrosine protein levels and expression of PDK1/AKT pathway proteins, while decreasing PI3K levels.
  • AKT expression remained unchanged, but PI3K expression was significantly decreased.

Conclusions:

  • Ritonavir (RTV) impairs sperm function potentially through alterations in the PI3K/PDK1/AKT pathway, driven by increased tyrosine phosphorylation.
  • The findings suggest RTV possesses male reproductive toxicity that warrants consideration for prescribers and users.
Keywords:
PI3K/PDK1/AKT pathwaycapacitationritonavirspermatozoa

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