Androgens and spermatogenesis

Ann Endocrinol (Paris). 2022 Jun;83(3):155-158. doi: 10.1016/j.ando.2022.04.010. Epub 2022 Apr 27.

Abstract

Male infertility contributes to 50% of all cases of infertility. The main cause is low quality and quantity of sperm. In humans, spermatogenesis starts at the beginning of puberty and lasts lifelong. It is under the control of FSH and testicular androgens, and mainly testosterone (T), and therefore requires a normal gonadotroph axis, intratesticular T production by Leydig cells and functional androgen receptors (ARs) within testicular Sertoli cells. Various clinical cases illustrate the roles of T in human spermatogenesis. Men with complete congenital hypogonadotropic hypogonadism (HH) are usually azoospermic. Treatment by exogenous testosterone injection and FSH is not able to produce sperm. However, combined treatment with FSH and hCG is effective. This example shows that intratesticular T plays a major role in spermatogenesis. Furthermore, testicular histology of men with LH receptor mutations shows Leydig cell hypoplasia/agenesis/dysplasia with conserved Sertoli cell count. The sperm count is reduced, as in males with partial inactivating mutation of the androgen receptor. Some protocols of hormonal male contraception or exogenous androgen abuse induce negative feedback in the hypothalamic pituitary axis, decreasing FSH, LH and T levels and inducing sperm defects and testicular atrophy. The time to recovery after cessation of drug abuse is around 14 months for sperm output and 38 months for sperm motility. In summary, abnormal androgen production and/or AR signaling impairs spermatogenesis in humans. The minimal level of intratesticular T for normal sperm production is a matter of debate. Interestingly, some animal models showed that completely T-independent spermatogenesis is possible, potentially through strong FSH activation. Finally, recent data suggest important roles of prenatal life and minipuberty in adult spermatogenesis.

Keywords: Androgens; Male infertility; Minipuberty; Sperm; Spermatogenesis; Testosterone.

MeSH terms

  • Androgens*
  • Animals
  • Disorder of Sex Development, 46,XY
  • Follicle Stimulating Hormone*
  • Humans
  • Male
  • Sperm Motility
  • Spermatogenesis
  • Testis / abnormalities
  • Testosterone / pharmacology

Substances

  • Androgens
  • Testosterone
  • Follicle Stimulating Hormone

Supplementary concepts

  • Leydig Cell Hypoplasia