Decrease of mitochondrial DNA level in sperm from patients infected with human immunodeficiency virus-1 linked to nucleoside analogue reverse transcriptase inhibitors.
OBJECTIVE
To study sperm parameters in patients infected with human immunodeficiency virus (HIV)-1 and to analyze mitochondrial DNA (mtDNA) in sperm according to the HIV treatment.


METHODS
Observational study.


METHODS
University-affiliated teaching hospital.


METHODS
Thirty-two patients infected with HIV-1 and 31 noninfected healthy men provided semen samples.


METHODS
None.


METHODS
After DNA extraction, mtDNA level was assessed using real-time polymerase chain reaction (PCR) (LightCycler) in whole semen and in selected spermatozoa from 90% density centrifugation gradients. For each sample, mtDNA and β-globin gene sequences were amplified and PCR products were quantified. The mtDNA-to-β-globin ratio expressed the number of mtDNA copies per cell.


RESULTS
Compared with the control group, several sperm parameters were altered in patients with HIV. The number of mtDNA copies per cell in whole semen was increased in HIV-infected patients (6.3±6.3 vs. 3.5±3.2). However, there was no statistically significant difference in mtDNA copy number in the spermatozoa obtained after density gradient centrifugation. The number of nucleoside analogue reverse transcriptase inhibitors (NRTI) taken by patients during treatment significantly influenced the mtDNA level in sperm (1 NRTI 7.6±8.1, 2 NRTIs 7.0±5.1, 3 NRTIs 3.2±2.1).


CONCLUSIONS
Using a specific method to measure sperm mtDNA, we demonstrated a decrease of mtDNA copies in spermatozoa after use of NRTIs with known mitochondrial toxicity.
Université de Toulouse, UPS, Groupe de Recherche en Fertilité Humaine (EA 3694, Human Fertility Research Group), TSA 70034, CECOS Midi Pyrénées, Hôpital Paule de Viguier, Toulouse, France.
Lynda
L
Pavili
Myriam
M
Daudin
Nathalie
N
Moinard
Marie
M
Walschaerts
Lise
L
Cuzin
Patrice
P
Massip
Christophe
C
Pasquier
Louis
L
Bujan
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000009:adverse effects* / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism
D004272:DNA, Mitochondrial; D009705:Nucleosides; D018894:Reverse Transcriptase Inhibitors