Thalita S Berteli1,2,3, Fang Wang4, Fabiana B Kohlrausch4,5, Caroline M Da Luz6,7, Fernanda V Oliveira6, David L Keefe4, Paula A Navarro6,7. 1. Department of Obstetrics and Gynecology, Langone Medical Center, New York University, New York, NY, USA. thalitabertelli@gmail.com. 2. Human Reproduction Division, Department of Gynecology and Obstetrics, Faculty of Medicine of Ribeirao Preto, Ribeirao Preto Medical School, University of Sao Paulo, 3900 Bandeirantes Avenue, Ribeirao Preto, SP, 14049-900, Brazil. thalitabertelli@gmail.com. 3. National Institute of Hormones and Women's Health, CNPq, Porto Alegre, RS, 90035-003, Brazil. thalitabertelli@gmail.com. 4. Department of Obstetrics and Gynecology, Langone Medical Center, New York University, New York, NY, USA. 5. Department of General Biology, Fluminense Federal University (UFF), Niterói, RJ, Brazil. 6. Human Reproduction Division, Department of Gynecology and Obstetrics, Faculty of Medicine of Ribeirao Preto, Ribeirao Preto Medical School, University of Sao Paulo, 3900 Bandeirantes Avenue, Ribeirao Preto, SP, 14049-900, Brazil. 7. National Institute of Hormones and Women's Health, CNPq, Porto Alegre, RS, 90035-003, Brazil.
Abstract
OBJECTIVE: Millions of babies have been conceived by IVF, yet debate about its safety to offspring continues. We hypothesized that superovulation and in vitro fertilization (IVF) promote genomic changes, including altered telomere length (TL) and activation of the retrotransposon LINE-1 (L1), and tested this hypothesis in a mouse model. MATERIAL AND METHODS: Experimental study analyzing TL and L1 copy number in C57BL/6 J mouse blastocysts in vivo produced from natural mating cycles (N), in vivo produced following superovulation (S), or in vitro produced following superovulation (IVF). We also examined the effects of prolonged culture on TL and L1 copy number in the IVF group comparing blastocysts cultured 96 h versus blastocysts cultured 120 h. TL and L1 copy number were measured by Real Time PCR. RESULTS: TL in S (n = 77; Mean: 1.50 ± 1.15; p = 0.0007) and IVF (n = 82; Mean: 1.72 ± 1.44; p < 0.0001) exceeded that in N (n = 16; Mean: 0.61 ± 0.27). TL of blastocysts cultured 120 h (n = 15, Mean: 2.14 ± 1.05) was significantly longer than that of embryos cultured for 96 h (n = 67, Mean: 1.63 ± 1.50; p = 0.0414). L1 copy number of blastocysts cultured for 120 h (n = 15, Mean: 1.71 ± 1.49) exceeded that of embryos cultured for 96 h (n = 67, Mean: 0.95 ± 1.03; p = 0.0162). CONCLUSIONS: Intriguingly ovarian stimulation, alone or followed by IVF, produced embryos with significantly longer telomeres compared to in vivo, natural cycle-produced embryos. The significance of this enriched telomere endowment for the health and longevity of offspring born from IVF merit future studies.
OBJECTIVE: Millions of babies have been conceived by IVF, yet debate about its safety to offspring continues. We hypothesized that superovulation and in vitro fertilization (IVF) promote genomic changes, including altered telomere length (TL) and activation of the retrotransposon LINE-1 (L1), and tested this hypothesis in a mouse model. MATERIAL AND METHODS: Experimental study analyzing TL and L1 copy number in C57BL/6 J mouse blastocysts in vivo produced from natural mating cycles (N), in vivo produced following superovulation (S), or in vitro produced following superovulation (IVF). We also examined the effects of prolonged culture on TL and L1 copy number in the IVF group comparing blastocysts cultured 96 h versus blastocysts cultured 120 h. TL and L1 copy number were measured by Real Time PCR. RESULTS: TL in S (n = 77; Mean: 1.50 ± 1.15; p = 0.0007) and IVF (n = 82; Mean: 1.72 ± 1.44; p < 0.0001) exceeded that in N (n = 16; Mean: 0.61 ± 0.27). TL of blastocysts cultured 120 h (n = 15, Mean: 2.14 ± 1.05) was significantly longer than that of embryos cultured for 96 h (n = 67, Mean: 1.63 ± 1.50; p = 0.0414). L1 copy number of blastocysts cultured for 120 h (n = 15, Mean: 1.71 ± 1.49) exceeded that of embryos cultured for 96 h (n = 67, Mean: 0.95 ± 1.03; p = 0.0162). CONCLUSIONS: Intriguingly ovarian stimulation, alone or followed by IVF, produced embryos with significantly longer telomeres compared to in vivo, natural cycle-produced embryos. The significance of this enriched telomere endowment for the health and longevity of offspring born from IVF merit future studies.
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