Nucleoside reverse transcriptase inhibitor-induced rat oocyte dysfunction and low fertility mediated by autophagy

Area of Science:

• Reproductive Biology
• Toxicology
• Cellular Biology

Background:

• Low fertility is a known side effect of nucleoside reverse transcriptase inhibitors (NRTIs).
• The precise molecular mechanisms behind NRTI-induced infertility remain largely unknown.
• Autophagy, a cellular degradation process, is implicated in various cellular dysfunctions.

Purpose of the Study:

• To investigate the role of autophagy in nucleoside reverse transcriptase inhibitor (NRTI)-induced oocyte dysfunction and reduced fertility in female rats.
• To elucidate the molecular mechanisms linking NRTIs to impaired reproductive capacity.

Main Methods:

• Both in vivo (Sprague-Dawley rats treated with zidovudine/AZT and lamivudine/3TC) and in vitro (isolated oocytes) experiments were performed.
• Oocytes were assessed for maturation, in vitro fertilization, mitochondrial function, apoptosis, and autophagy.
• Autophagy inhibition was achieved using 3-methyladenine (3-MA).

Main Results:

• NRTI treatment led to a time-dependent decrease in oocyte maturation markers, fertilization and cleavage rates, blastocyst formation, mitochondrial DNA copy number, and ATP levels.
• NRTI exposure significantly increased reactive oxygen species and apoptosis in oocytes.
• Autophagy inhibition partially reversed these NRTI-induced detrimental effects on oocytes.

Conclusions:

• Nucleoside reverse transcriptase inhibitors (NRTIs) demonstrably cause oocyte dysfunction and low fertility in rats.
• Autophagy is a significant mediator of the damage induced by NRTIs in rat oocytes.
• Targeting autophagy may offer a potential strategy to mitigate NRTI-related infertility.