López Sònia, Coll Oriol, Durban Mercè, Hernàndez Sandra, Vidal Ricard, Suy Anna, Morén Constanza, Casademont Jordi, Cardellach Francesc, Mataró Daniel, Miró Oscar, Garrabou Glòria
Mitochondrial Research Laboratory, Internal Medicine Department, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain.
Antivir Ther. 2008;13(6):833-8.
HIV-infected women under highly active antiretroviral therapy (HAART) undergoing in vitro fertilization (IVF) have a lower pregnancy rate than noninfected controls, which depends on oocyte-related factors. We hypothesized that mitochondrial toxicity caused by antiretrovirals could be the underlying mechanism of such disturbance.
We have studied 16 and 19 frozen-thawed oocytes obtained after oocyte retrieval IVF cycles from 8 and 14 infertile HIV-infected and uninfected women, respectively, matched by age. At inclusion, HIV-positive women had been infected for >13 years and had received HAART for >9 years, including at least one nucleoside reverse transcriptase inhibitor. All of them had undetectable HIV viral load and a good immunological status. Mitochondrial DNA (mtDNA) content was determined by quantitative real-time PCR in each individual oocyte.
HIV-infected infertile women on HAART showed significant oocyte mtDNA depletion when compared with uninfected controls (32% mtDNA decrease, P<0.05). This oocyte mtDNA depletion was even greater on those HIV-infected women who failed to become pregnant when compared with controls (39% mtDNA decrease, P=0.03). No significant correlation was found between mtDNA oocyte content and cumulative doses of antiretrovirals or the immunological status of HIV patients.
Oocytes from infertile HIV-infected HAART-treated women show decreased mtDNA content, and this could explain their poor reproductive outcome.
接受高效抗逆转录病毒治疗（HAART）的HIV感染女性在进行体外受精（IVF）时，其妊娠率低于未感染的对照组，这取决于与卵母细胞相关的因素。我们推测抗逆转录病毒药物引起的线粒体毒性可能是这种干扰的潜在机制。
我们分别研究了从8名和14名年龄匹配的HIV感染和未感染的不孕女性的卵母细胞取卵IVF周期后获得的16个和19个冻融卵母细胞。纳入研究时，HIV阳性女性已感染超过13年，并接受HAART超过9年，包括至少一种核苷类逆转录酶抑制剂。她们所有人体内的HIV病毒载量均检测不到，且免疫状态良好。通过定量实时PCR测定每个卵母细胞中的线粒体DNA（mtDNA）含量。
与未感染的对照组相比，接受HAART的HIV感染不孕女性的卵母细胞mtDNA明显减少（mtDNA减少32%，P<0.05）。与对照组相比，那些未怀孕的HIV感染女性的卵母细胞mtDNA减少更为明显（mtDNA减少39%，P=0.03）。mtDNA卵母细胞含量与抗逆转录病毒药物的累积剂量或HIV患者的免疫状态之间未发现显著相关性。
接受HAART治疗的HIV感染不孕女性的卵母细胞显示mtDNA含量降低，这可能解释了她们较差的生殖结局。
