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17α-estradiol does not adversely affect sperm parameters or fertility in male mice: implications for reproduction-longevity trade-offs

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Abstract

17α-estradiol (17α-E2) is referred to as a nonfeminizing estrogen that was recently found to extend healthspan and lifespan in male, but not female, mice. Despite an abundance of data indicating that 17α-E2 attenuates several hallmarks of aging in male rodents, very little is known with regard to its effects on feminization and fertility. In these studies, we evaluated the effects of 17α-E2 on several markers of male reproductive health in two independent cohorts of mice. In alignment with our previous reports, chronic 17α-E2 treatment prevented gains in body mass, but did not adversely affect testes mass or seminiferous tubule morphology. We subsequently determined that chronic 17α-E2 treatment also did not alter plasma 17β-estradiol or estrone concentrations, while mildly increasing plasma testosterone levels. We also determined that chronic 17α-E2 treatment did not alter plasma follicle-stimulating hormone or luteinizing hormone concentrations, which suggests 17α-E2 treatment does not alter gonadotropin-releasing hormone neuronal function. Sperm quantity, morphology, membrane integrity, and various motility measures were also unaffected by chronic 17α-E2 treatment in our studies. Lastly, two different approaches were used to evaluate male fertility in these studies. We found that chronic 17α-E2 treatment did not diminish the ability of male mice to impregnate female mice, or to generate successfully implanted embryos in the uterus. We conclude that chronic treatment with 17α-E2 at the dose most commonly employed in aging research does not adversely affect reproductive fitness in male mice, which suggests 17α-E2 does not extend lifespan or curtail disease parameters through tradeoff effects with reproduction.

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Funding

This work was supported by Coordination for the Improvement of Higher Education Personnel (CAPES) (J. V. V. I.), Brazilian National Council for Scientific and Technological Development (CNPq) (A. S.), Research Support Foundation of the State of Rio Grande do Sul (FAPERGS) (A. S.), and the National Institutes of Health (R01 AG069742 to M. B. S.).

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Authors and Affiliations

  1. Aging & Metabolism Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Chapman S212, Oklahoma City, OK, 73104, USA

    José V. V. Isola & Michael B. Stout

  2. Faculdade de Veterinária, Universidade Federal de Pelotas, Pelotas, RS, Brazil

    José V. V. Isola, Camila R. C. de Brito, Bianka M. Zanini, Arnaldo D. Vieira, Bernardo G. Gasperin & Augusto Schneider

  3. Faculdade de Nutrição, Universidade Federal de Pelotas, Rua Gomes Carneiro, 1, Pelotas, RS, 96010-610, Brazil

    Gabriel B. Veiga, Driele N. Garcia, Jéssica D. Hense & Augusto Schneider

  4. Facultad de Ciencias Agropecuarias, Universidad de La Salle, Campus Utopía, Yopal, Casanare, Colombia

    Joao A. Alvarado-Rincón

  5. Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand

    Michael Garratt

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  1. José V. V. Isola
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Isola, J.V.V., Veiga, G.B., de Brito, C.R.C. et al. 17α-estradiol does not adversely affect sperm parameters or fertility in male mice: implications for reproduction-longevity trade-offs. GeroScience 45, 2109–2120 (2023). https://doi.org/10.1007/s11357-022-00601-8

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