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A pilot study of LINE-1 copy number and telomere length with aging in human sperm

  • Gamete Biology
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Unlike other cells in the body, in sperm, telomere length (TL) increases with age. TL can regulate nearby genes, and the subtelomeric region is rich in retrotransposons. We hypothesized that age-related telomere lengthening in sperm might suppress Long Interspersed Element 1 (LINE-1/L1), the only competent retrotransposon in humans.

Methods

We measured L1 copy number (L1-CN) and sperm telomere length (STL) from young and older men to evaluate the relationship between age, TL and L1-CN. We also evaluated L1-CN and TL in individual sperm to determine whether these variables influence sperm morphology. STL was assayed by Multiplex quantitative polymerase chain reaction method (mmqPCR) and L1-CN by Quantitative polymerase chain reaction (qPCR).

Results

We found that STL increased, and L1-CN decreased significantly with paternal age. STL in normal single sperm was significantly higher than in abnormal sperm. L1-CN did not differ between normal and abnormal sperm. Furthermore, morphologically normal sperm have longer telomeres than abnormal sperm.

Conclusions

Elongation of telomeres in the male germline could repress retrotransposition, which tends to increase with cellular aging. More studies in larger cohorts across a wide age span are needed to confirm our conclusions and explore their biological and clinical significance.

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Data availability

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

Abbreviations

CoV:

Coefficient of variation

DTT:

Dithiothreitol

EDTA:

Ethylenediaminetetraacetic acid

gDNA:

Genomic DNA

ICSI:

Intracytoplasmic sperm injection

IRB:

Institutional Review Board

IQR:

Interquartile range

L1:

Long interspersed element 1

L1-CN:

L1 copy number

Long Interspersed Element 1:

LINE-1/L1

mmqPCR:

Multiplex quantitative polymerase chain reaction method

non-LTR:

TE-non-long terminal repeat

NTC:

Non-template control

NYU:

New York University

NYUFC:

New York University Langone Fertility Center

ORFs:

Open reading frames

piRNA:

PIWI-interacting RNA

PTC:

Positive control

PVP:

Polyvinylpyrrolidone

qPCR:

Quantitative polymerase chain reaction

rDNA:

Recombinant DNA

RT:

Reverse transcriptase

RUES:

Rockefeller University

SC-qPCR:

Single-cell telomere length assay

STL:

Sperm telomere length

TEs:

Transposable elements

TL:

Telomere length

TPE:

Telomere position effect

WHO:

World Health Organization

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Acknowledgements

Coordination for the Improvement of Higher Education Personnel (CAPES, Finance Code: 001, Brazil; process n. 88887.371487/2019-00 and process n. 88887.597054/2021-00 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).

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Correspondence to Thalita S. Berteli.

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Berteli, T.S., Wang, F., Navarro, P.A. et al. A pilot study of LINE-1 copy number and telomere length with aging in human sperm. J Assist Reprod Genet 40, 1845–1854 (2023). https://doi.org/10.1007/s10815-023-02857-1

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