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

Abstract

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. Experimental study analyzing TL and L1 copy number in C57BL/6J 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 96h versus blastocysts cultured 120h. TL and L1 copy number were measured by Real Time PCR. 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 120h (n = 15, Mean: 2.14 ± 1.05) was significantly longer than that of embryos cultured for 96h (n = 67, Mean: 1.63 ± 1.50; p = 0.0414). L1 copy number of blastocysts cultured for 120h (n = 15, Mean: 1.71 ± 1.49) exceeded that of embryos cultured for 96h (n = 67, Mean: 0.95 ± 1.03; p = 0.0162). 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.