Nucleoside analog stavudine depletes mitochondrial DNA with no organelle loss in mouse oocytes.
Nucleoside reverse transcriptase inhibitors (NRTIs) are the basis of antiretroviral treatment of HIV-positive patients. Several studies have shown decreased fertility and fecundity among HIV-positive women under antiretroviral treatment. Oocyte impaired competence has been hypothesized to be one of the main mechanisms underlying of this decreased fertility. NRTI side effects are thought to be due to the induced mitochondrial dysfunction. Stavudine, a widely used NRTI, causes persistent mitochondrial damage in various tissues. In order to gain insights into possible mechanisms of HIV-related diminished fertility, we studied the effects of stavudine on mouse oocyte mitochondria. Mitochondrial volume, protein assay and ATP contents were unaltered by stavudine treatment, but we found mitochondrial Cox I depletion in liver and oocytes. Our findings suggest that stavudine induces mtDNA depletion without organelle loss in mouse oocytes. The decrease in Cox I DNA in treated oocytes likely points to mitochondrial dysfunction, which can impair chances of pregnancy and embryo viability. We propose that the competence of oocytes depends primarily on functional capacity of mitochondria and less on their number.
Bostan
Alionka
A
Human Reproduction Research Laboratory, Université Libre de Bruxelles, Campus Erasme, GE 2.2.214, Route de Lennik 808, 1070 Brussels, Belgium. abostan@ulb.ac.be
Demeestere
Isabelle
I
Vanderwinden
Jean-Marie
JM
Devreker
Fabienne
F
Englert
Yvon
Y
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D005260:Female; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009865:Oocytes / Q000187:drug effects*; D015388:Organelles / Q000187:drug effects; D018119:Stavudine / Q000494:pharmacology*
D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D008565:Membrane Proteins; D000255:Adenosine Triphosphate; D018119:Stavudine; D051545:Cyclooxygenase 1; C496512:Ptgs1 protein, mouse