Spermatozoa telomeres determine telomere length in early embryos and offspring

Abstract

Offspring telomere length (TL) has been correlated with paternal TL, but the mechanism for this parent of origin-specific inheritance remains unclear. The objective of this study has been to determine the role of spermatozoa TL in embryonic telomere lengthening by using two mouse models showing dimorphism in their spermatozoa TL: Mus musculus vs Mus spretus and old vs young Mus musculus. Mus spretus spermatozoa displayed a shorter TL than Mus musculus. Hybrid offspring exhibited lower TL compared with Mus musculus starting at the two-cell stage, before the onset of telomerase expression. To analyze the role of spermatozoa telomeres in early telomere lengthening, we compared the TL in oocytes, zygotes, two-cell embryos and blastocysts produced by parthenogenesis or by fertilization with Mus musculus or Mus spretus spermatozoa. TL was significantly higher in spermatozoa compared with oocytes, and it increased significantly from the oocyte to the zygote stage in those embryos fertilized with Mus musculus spermatozoa, but not in those fertilized with Mus spretus spermatozoa or produced by parthenogenesis. A further increase was noted from the zygote to the two-cell stage in fertilized Mus musculus embryos, whereas hybrid embryos maintained the oocyte TL. Spermatozoa TL shortened with age in Mus musculus and the offspring from young males showed a significantly higher TL compared with that fathered by old males. These significant differences were already noticeable at the two-cell stage. These results suggest that spermatozoa telomeres act as a guide for telomerase-independent telomere lengthening resulting in differences in TL that persist after birth. Free Spanish abstract: A Spanish translation of this abstract is freely available at

Semen preparation methods and sperm telomere length: density gradient centrifugation versus the swim up procedure

“…What’s more, the sperm with short telomeres derived from the late generation of telomerase-null mice (TR −/− ) would have some bad influence on the fertilization and embryonic development, More specifically, fertilization of TR −/− sperm with wild-type eggs exhibited low rates of cleavage and development to morula and blastocysts14. Moreover, our previous study demonstrated a positive correlation between the telomere length and embryo quality in the early stages of development15, and another study reported that spermatozoa telomeres determine the telomere length of early embryos and offspring16. A recent report also showed that the STL could be used as a new parameter in diagnosing infertility in males17.…”

Longitudinal analysis of somatic and germ‐cell telomere dynamics in outbred mice

“…A previous study suggested that the ALT mechanism could be active during spermatogenesis in humans, based on an unexpected age‐related increase in sperm TL in the absence of telomerase (Antunes et al, ). This mechanism has been described also in the absence of telomerase activity after oocyte fertilization and activation (de Frutos et al, ; Liu et al, ). Interestingly, we observed upregulation of Zscan4 in old mouse testicles, and ZSCAN4 protein was localized in the nucleus of spermatocytes and spermatids, pointing to an active ALT mechanism during meiotic and postmeiotic stages.…”

“…It could be that longer telomeres in the sperm of old males somehow compensate for the short telomeres of aged oocytes. Further, it has been also described that sperm telomeres act as guides for intratelomeric alternative telomere lengthening of the early embryo's telomeres after fertilization (de Frutos et al, ).…”

“…To check if the collection protocol gave rise to a similar DNA content in all the oocytes, genomic DNA ( Rn18S ) was quantified in five samples per group. qPCR was performed using a Rotor Gene 6000 Real‐Time PCR machine (Corbett Research; 94°C 3 min followed by 40 cycles of 94°C 10 s, 60°C 30 s, and 72°C 30 s; de Frutos et al, ).…”

“…The small quantity of DNA in these samples precludes the use of relative qPCR (i.e., data normalization to an internal control). Thus, absolute qPCR was performed as previously described (de Frutos et al, ). Cycle threshold ( C t ) values were directly compared to the group with the highest average C t (i.e., shortest TL) without data normalization to internal control.…”