1 / 1

Evaluation of Pregnancy PBMC and Placental MtDNA in HIV-infected,

Oak Tree Clinic. Placenta maternal side. Placenta fetal side. P=0.058. P=0.563. 250. 250. 300. 300. A = HAART 2. A= HAART 2. trimester. trimester. nd. nd. 200. 200. B= HAART conception. B = HAART at conception. 250. 250. mtDNA/nDNA. C = HIV. C= HIV. -. -. controls.

kelii
Download Presentation

Evaluation of Pregnancy PBMC and Placental MtDNA in HIV-infected,

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Oak Tree Clinic Placenta maternal side Placenta fetal side P=0.058 P=0.563 250 250 300 300 A = HAART 2 A= HAART 2 trimester trimester nd nd 200 200 B= HAART conception B = HAART at conception 250 250 mtDNA/nDNA C = HIV C= HIV - - controls controls mtDNA/nDNA 150 150 ratio 100 200 200 nDNA 100 50 50 150 150 PBMC mtDNA/ A N=30 C N=23 A N=30 C N=23 0 0 100 100 50 50 13 13 - - 23 23 >23 >23 - - 30 30 >30 >30 - - 39 39 Delivery Delivery 6 weeks 6 weeks Weeks Weeks Weeks Weeks Weeks Weeks Post Post - - partum partum N 14 22 28 17 28 Period in pregnancy N 5 7 8 5 8 N 21 22 21 20 Placenta mtDNA/nDNA maternal vs . fetal Group N MATERNAL FETAL Pearson's correlations paired comparisons mean ± standard error R slope p value p value A 30 97 ± 7 90 ± 7 0.476 0.504 0.008 0.052 B 7 81 ± 8 84 ± 15 0.719 0.359 0.069 0.938 C 23 84 ± 8 85 ± 10 0.899 1.05 <0.0001 0.223 Hélène C.F. Côté helene.cote@ubc.ca Ph: 604-822-9777 FAX: 604-822-7635 948 Evaluation of Pregnancy PBMC and Placental MtDNA in HIV-infected, HAART-treated women, compared to HIV-uninfected women* Hélène Côté*1,2, Evelyn Maan3, Eszter Papp1, Tessa Chaworth-Musters3, Izabelle Gadawski1, Julie van Schalkwyk3, Marissa Jitratkosol3, John Forbes2,3, David Burdge2,3, Deborah Money2,3, and The HIV Perinatal Study Group 1University of British Columbia; 2Women`s Health Research Institute; and 3 Oak Tree Clinic / Children`s & Women`s Health Centre of BC, Vancouver, British Columbia, Canada Background Results Figure 3. Comparison of infant blood mtDNA content between groups at birth (0-3 days of age). Figure 2. Comparison of placental mtDNA content between groups A and C on the maternal and fetal side. • HIV-infected women receive HAART during pregnancy, either from the 2nd trimester until delivery, or throughout the pregnancy if indicated by CD4 count. • NRTI can cause mitochondrial toxicity and are known to cross the placenta. • This study evaluated longitudinal peripheral blood mononucleated cells (PBMC) and placental tissue mitochondrial DNA (mtDNA) levels in HIV-positive pregnancies compared to control HIV-negative pregnancies, as well as whole blood mtDNA levels in the infants at birth. Group A: N=27 for longitudinal PBMC, N=30 for placenta, HIV+ on HAART since 2nd trimester of pregnancy (mostly AZT/3TC/nelfinavir HAART regimen) Group B: N=8 for longitudinal PBMC, 7 for placenta, HIV+ on HAART since conception (regimen varied) Group C: N=24 for PBMC, 23 for placenta: HIV negative controls P=0.285 P=0.121 P=0.518 350 300 250 Blood mtDNA/nDNA Figure 1. Longitudinal mean ± standard error maternal PBMC mtDNA content during pregnancy. 200 150 100 50 Methods A N=26 C N=19 B N=8 • Prospective single centre cohort study. • Blood was collected in CPT tubes (BD) at 4 time periods in all pregnancies: 13-23w of gestation (before HAART for Group A), >23-30w, >30-39w, delivery (when possible) and for HIV pregnancies, at 6w post-partum. PBMC were isolated and washed in PBS 3 times at low speed. • Whole blood was collected from infants (PKU heel prick) within 3 days of birth. • Placental tissue was collected from fetal and maternal sides shortly after delivery. • MtDNA content was measured in isolated maternal PBMC, infant whole blood and placental tissue by real-time PCR. • Statistical analyses: Between group comparisons were done using the Mann-Whitney test. For placenta maternal vs. fetal side analyses, Wilcoxon signed-rank test and Pearson’s correlation were used. Conclusions Figure 4. Correlation between placenta mtDNA content, maternal vs. fetal side. • A physiological increase in PBMC mtDNA is seen in normal pregnancy near the end of gestation, possibly to meet high energy demands. This increase appears delayed in HIV+ HAART-treated pregnancies. • In HIV+ HAART-treated pregnancies, placental mtDNA tends to be higher on the maternal side compared to the fetal side of the organ. • Changes in placental mtDNA may affect metabolism and energy production within the placenta. • Infant blood mtDNA at birth content was not different between groups. • Mitochondrial toxicity related to nucleoside therapy may have amplified consequences in a perinatal setting. • Further studies are needed to identify antiretrovirals with the least toxicity in pregnancy. Group A = HIV+ HAART-exposed * Values presented here are slightly different from those in the abstract as a study participant originally been placed in Group B belonged in Group A 300 250 200 fetal side mtDNA/nDNA 150 100 50 0 Acknowledgements 0 50 100 150 200 250 300 maternal side mtDNA/nDNA Table 1. Placental mtDNA content. The Perinatal HIV Study Group also includes: Ariane Alimenti Group C = HIV- controls 300 250 200 Funding to D. Money from: fetal side mtDNA/nDNA 150 100 50 0 0 50 100 150 200 250 300 maternal side mtDNA/nDNA

More Related