Dynamic regulation of gonadal transposon control across the lifespan of the naturally short-lived African turquoise killifish

Bryan B. Teefy; Ari Adler; Alan Xu; Katelyn Hsu; Param Priya Singh; Bérénice A. Benayoun

doi:10.1101/gr.277301.122

Dynamic regulation of gonadal transposon control across the lifespan of the naturally short-lived African turquoise killifish

¹Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California 90089, USA;
²Molecular and Computational Biology Department, USC Dornsife College of Letters, Arts and Sciences, Los Angeles, California 90089, USA;
³Department of Genetics, Stanford University, Stanford, California 94305, USA;
⁴Biochemistry and Molecular Medicine Department, USC Keck School of Medicine, Los Angeles, California 90089, USA;
⁵USC Norris Comprehensive Cancer Center, Epigenetics and Gene Regulation, Los Angeles, California 90089, USA;
⁶USC Stem Cell Initiative, Los Angeles, California 90089, USA

↵Present addresses: ⁷Department of Anatomy, University of California San Francisco, San Francisco, CA 94143, USA; ⁸UCSF Bakar Aging Research Institute, San Francisco, CA 94143, USA

Corresponding author: berenice.benayoun{at}usc.edu

Abstract

Although germline cells are considered to be functionally “immortal,” both the germline and supporting somatic cells in the gonad within an organism experience aging. With increased age at parenthood, the age-related decline in reproductive success has become an important biological issue for an aging population. However, molecular mechanisms underlying reproductive aging across sexes in vertebrates remain poorly understood. To decipher molecular drivers of vertebrate gonadal aging across sexes, we perform longitudinal characterization of the gonadal transcriptome throughout the lifespan in the naturally short-lived African turquoise killifish (Nothobranchius furzeri). By combining mRNA-seq and small RNA-seq from 26 individuals, we characterize the aging gonads of young-adult, middle-aged, and old female and male fish. We analyze changes in transcriptional patterns of genes, transposable elements (TEs), and piRNAs. We find that testes seem to undergo only marginal changes during aging. In contrast, in middle-aged ovaries, the time point associated with peak female fertility in this strain, PIWI pathway components are transiently down-regulated, TE transcription is elevated, and piRNA levels generally decrease, suggesting that egg quality may already be declining at middle-age. Furthermore, we show that piRNA ping-pong biogenesis declines steadily with age in ovaries, whereas it is maintained in aging testes. To our knowledge, this data set represents the most comprehensive transcriptomic data set for vertebrate gonadal aging. This resource also highlights important pathways that are regulated during reproductive aging in either ovaries or testes, which could ultimately be leveraged to help restore aspects of youthful reproductive function.

Footnotes

[Supplemental material is available for this article.]
Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.277301.122.

Received September 9, 2022.
Accepted December 23, 2022.

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