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Age-related changes in human Leydig cell status.

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Aging reduces Leydig cell number and insulin-like factor 3 (INSL3) expression in men. However, aged Leydig cells retain their in vitro androgen production capacity, suggesting preserved hormonal function despite cell loss.

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Area of Science:

  • Reproductive biology and endocrinology
  • Aging research
  • Human physiology

Background:

  • Aging is associated with decreased serum testosterone, testicular involution, and reduced spermatogenesis.
  • Previous studies on aged testes often focused on single features or used tissue from cancer patients.
  • A comprehensive understanding of age-related changes in human Leydig cells and their function is lacking.

Purpose of the Study:

  • To investigate the consequences of aging on human Leydig cell number and hormonal function.
  • To examine the relationship between Leydig cell number, Sertoli cell number, and INSL3 expression with age.
  • To assess the in vitro androgenic potential of Leydig cells from aged versus young men.

Main Methods:

  • Analysis of testis biopsies from organ donors and patients with complete spermatogenesis (age range 19-85 years).
  • Quantification of Leydig and Sertoli cells using immunohistochemistry.
  • Measurement of INSL3 and steroidogenic enzyme gene expression via qRT-PCR.
  • Assessment of androgen secretion from in vitro cultured testicular fragments using LC-MS/MS.

Main Results:

  • Leydig cell number and Sertoli cell number significantly decreased with increasing age.
  • A strong positive correlation was found between Leydig and Sertoli cell numbers across all ages.
  • INSL3 mRNA expression declined in parallel with Leydig cell number and age.
  • In vitro androgen production capacity of Leydig cells did not differ between young and old donors.

Conclusions:

  • Aging leads to a reduction in human Leydig and Sertoli cell numbers, with a strong interdependency between these cell types.
  • While Leydig cell number and INSL3 expression decrease with age, their in vitro androgen production capacity remains intact.
  • These findings offer insights into the regulation of intratesticular androgens during human aging and may be relevant for understanding male reproductive disorders in the elderly.