Zidovudine inhibits telomere elongation, increases the transposable element LINE-1 copy number and compromises mouse embryo development

Author(s)

Navarro, Paula A. ^{[1, 2]} ; Wang, Fang ^[1] ; Pimentel, Ricardo ^[1] ; Robinson, Jr., Leroy George ^[1] ; Berteli, Thalita S. ^{[1, 2]} ; Keefe, David L. ^[1]

Affiliation

^[1] NYU Langone Med Ctr, Dept Obstet & Gynecol, New York, NY 10016 - USA

^[2] Univ Sao Paulo, Dept Gynecol & Obstet, Fac Med Ribeirao Preto, 3900 Bandeirantes Ave, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: MOLECULAR BIOLOGY REPORTS; v. 48, n. 12 OCT 2021.
• Web of Science Citations: 0

Abstract

Purpose Millions of pregnant, HIV-infected women take reverse transcriptase inhibitors, such as zidovudine (azidothymidine or AZT), during pregnancy. Reverse transcription plays important roles in early development, including regulation of telomere length (TL) and activity of transposable elements (TE). So we evaluated the effects of AZT on embryo development, TL, and copy number of an active TE, Long Interspersed Nuclear Element 1 (LINE-1), during early development in a murine model. Design Experimental study. Methods In vivo fertilized mouse zygotes from B6C3F1/B6D2F1 mice were cultured for 48 h in KSOM with no AZT (n = 45), AZT 1 mu M (n = 46) or AZT 10 mu M (n = 48). TL was measured by single-cell quantitative PCR (SC-pqPCR) and LINE-1 copy number by qPCR. The percentage of morulas at 48 h, TL and LINE-1 copy number were compared among groups. Results Exposure to AZT 1 mu M or 10 mu M significantly impairs early embryo development. TL elongates from oocyte to control embryos. TL in AZT 1 mu M embryos is shorter than in control embryos. LINE-1 copy number is significantly lower in oocytes than control embryos. AZT 1 mu M increases LINE-1 copy number compared to oocytes controls, and AZT 10 mu M embryos. Conclusion AZT at concentrations approaching those used to prevent perinatal HIV transmission compromises mouse embryo development, prevents telomere elongation and increases LINE-1 copy number after 48 h treatment. The impact of these effects on the trajectory of aging of children exposed to AZT early during development deserves further investigation. (AU)

• FAPESP's process: 15/21907-0 - Accuracy of polar body mean telomere length and polar body shortest telomere length of human oocytes obtained after controlled ovarian stimulation for assisted reproduction techniques in predicting embryonic euploidia and aneuploidy
• Grantee: Paula Andrea de Albuquerque Salles Navarro
• Support Opportunities: Scholarships abroad - Research