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Impact of superovulation and in vitro fertilization on LINE-1 copy number and telomere length in C57BL/6 J mice blastocysts

Molecular Biology Reports volume 49, pages 4909–4917 (2022)Cite this article

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.

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Data availability

The data underlying this study will be shared on reasonable request to the corresponding author.

Code availability

Not applicable.

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Funding

Coordination for the Improvement of Higher Education Personnel (CAPES, Finance Code: 001, Brazil; Grant number 88887.371487/2019-00 to TSB), Brazilian National Council for Scientific and Technological Development (CNPq, Brazil; Grant number 204747/2018-0 to FBK) and the Stanley H. Kaplan Fund of the NYU Grossman School of Medicine (to DLK). These data has been presented previously at 77th ASRM Scientific Congress & Expo: vol. 116, issue 3, Suppl: E168-E169, September 01. 2021, https://doi.org/10.1016/j.fertnstert.2021.07.465.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Langone Medical Center, New York University, New York, NY, USA

    Thalita S. Berteli, Fang Wang, Fabiana B. Kohlrausch & David L. Keefe

  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

    Thalita S. Berteli, Caroline M. Da Luz, Fernanda V. Oliveira & Paula A. Navarro

  3. National Institute of Hormones and Women’s Health, CNPq, Porto Alegre, RS, 90035-003, Brazil

    Thalita S. Berteli, Caroline M. Da Luz & Paula A. Navarro

  4. Department of General Biology, Fluminense Federal University (UFF), Niterói, RJ, Brazil

    Fabiana B. Kohlrausch

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  1. Thalita S. Berteli
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Correspondence to Thalita S. Berteli.

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This study was approved by the Faculty of Medicine of Ribeirão Preto Ethics Committee on the Use of Animals, under the number CEUA-FMRP/USP-107/2017.

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Berteli, T.S., Wang, F., Kohlrausch, F.B. et al. Impact of superovulation and in vitro fertilization on LINE-1 copy number and telomere length in C57BL/6 J mice blastocysts. Mol Biol Rep 49, 4909–4917 (2022). https://doi.org/10.1007/s11033-022-07351-y

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