Literature DB >> 32914138

Short-acting testosterone appears to have lesser effect on male reproductive potential compared to long-acting testosterone in mice.

Kevin Y Chu1, Shathiyah Kulandavelu2, Thomas A Masterson1, Emad Ibrahim1, Himanshu Arora1, Ranjith Ramasamy1.   

Abstract

OBJECTIVE: To compare the effect of exogenous short-acting and long-acting testosterone on male reproductive potential in mice.
DESIGN: In vivo mouse model.
SETTING: University-based basic science research laboratory. ANIMALS: A total of 30 wild-type C57BL/6 male and female mice were used for this experimentation. The male mice were used for control group and testosterone supplementation, while both male and female mice were used for the breeding portion of the study.
INTERVENTIONS: Exogenous testosterone was administered either in short-acting formulation (Monday-Wednesday-Friday dosing schedule, testosterone propionate 0.2 mg/kg), or long-acting formulation (3-month dosing schedule - testosterone pellets 150 mg) to male mice. MAIN OUTCOME MEASURES: Time to pregnancy, Luteinizing hormone (LH) levels, and testicular weight.
RESULTS: Mice treated with long-acting testosterone appear to have longer time to pregnancy when compared to wild-type (33 ± 11 vs 23 ± 2.6 days, p ≤ 0.05) and mice that received short-acting testosterone propionate (26 ± 5.9 days). Mice treated with long-acting testosterone had smaller testes weight when compared to control (0.08 ± 0.01 vs 0.11 ± 0.01g; p ≤ 0.01), while the short-acting testosterone treated mice had similar testis weight when compared to control (0.09 ± 0.02 vs 0.11 ± 0.01g; ns). The serum testosterone level was elevated in mice that received testosterone pellets (285.78 ng/dL) and testosterone propionate (122.16 ng/dL) versus control (68.4 ng/dL). In mice that received long-acting testosterone pellets, LH levels at 3 months were almost undetectable while those that received short-acting testosterone remained similar to control (0.017 ± 0.058 vs 0.348 ± 0.232 IU/L; p ≤ 0.01). Female reproductive potential parameters including litter size and pup weight were collected and observed to have no difference between groups.
CONCLUSION: Through a mouse breeding study, mice that received short-acting testosterone were shown to have fertility potential similar to wild-type male mice. Long-acting exogenous testosterone appeared to impair male reproductive capacity and LH levels when compared to short-acting testosterone. Short-acting testosterone appeared to cause less LH suppression. Identifying strategies to increase testosterone while simultaneously preserving male fertility is important for treating young men with hypogonadism.

Entities:  

Keywords:  male infertility; mouse model; reproductive potential; testosterone

Mesh:

Substances:

Year:  2020        PMID: 32914138      PMCID: PMC7480784          DOI: 10.1016/j.xfss.2020.03.002

Source DB:  PubMed          Journal:  F S Sci        ISSN: 2666-335X


  22 in total

1.  Duration of spermatogenesis in the mouse and timing of stages of the cycle of the seminiferous epithelium.

Authors:  E F OAKBERG
Journal:  Am J Anat       Date:  1956-11

2.  Contraceptive efficacy of testosterone-induced azoospermia and oligozoospermia in normal men.

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Journal:  Fertil Steril       Date:  1996-04       Impact factor: 7.329

Review 3.  Novel Therapy for Male Hypogonadism.

Authors:  Robert Carrasquillo; Kevin Chu; Ranjith Ramasamy
Journal:  Curr Urol Rep       Date:  2018-06-09       Impact factor: 3.092

4.  Natesto Effects on Reproductive Hormones and Semen Parameters: Results from an Ongoing Single-center, Investigator-initiated Phase IV Clinical Trial.

Authors:  Thomas Masterson; Manuel Molina; Emad Ibrahim; Ranjith Ramasamy
Journal:  Eur Urol Focus       Date:  2018-09-01

5.  Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging.

Authors:  S M Harman; E J Metter; J D Tobin; J Pearson; M R Blackman
Journal:  J Clin Endocrinol Metab       Date:  2001-02       Impact factor: 5.958

Review 6.  GnRH pulse frequency-dependent differential regulation of LH and FSH gene expression.

Authors:  Iain R Thompson; Ursula B Kaiser
Journal:  Mol Cell Endocrinol       Date:  2013-09-19       Impact factor: 4.102

7.  Changing relationships between testis size, Sertoli cell number and spermatogenesis in Sprague-Dawley rats.

Authors:  W E Berndtson; T L Thompson
Journal:  J Androl       Date:  1990 Sep-Oct

Review 8.  The effects of advanced paternal age on fertility.

Authors:  Jason R Kovac; Josephine Addai; Ryan P Smith; Robert M Coward; Dolores J Lamb; Larry I Lipshultz
Journal:  Asian J Androl       Date:  2013-08-05       Impact factor: 3.285

9.  Prevalence of symptomatic androgen deficiency in men.

Authors:  Andre B Araujo; Gretchen R Esche; Varant Kupelian; Amy B O'Donnell; Thomas G Travison; Rachel E Williams; Richard V Clark; John B McKinlay
Journal:  J Clin Endocrinol Metab       Date:  2007-08-14       Impact factor: 5.958

10.  Pharmacokinetics and pharmacodynamics of subcutaneous testosterone implants in hypogonadal men.

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Journal:  Clin Endocrinol (Oxf)       Date:  1996-07       Impact factor: 3.478

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  1 in total

1.  Short-Acting Testosterone: More Physiologic?

Authors:  Gerwin Westfield; Ursula B Kaiser; Dolores J Lamb; Ranjith Ramasamy
Journal:  Front Endocrinol (Lausanne)       Date:  2020-09-30       Impact factor: 5.555

  1 in total

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