Ryanodine receptors are expressed and functionally active in mouse spermatogenic cells and their inhibition interferes with spermatogonial differentiation

J Cell Sci. 2004 Aug 15;117(Pt 18):4127-34. doi: 10.1242/jcs.01283. Epub 2004 Jul 27.

Abstract

Ryanodine receptors (RyRs) are intracellular calcium release channels that are highly expressed in striated muscle and neurons but are also detected in several non-excitable cells. We have studied the expression of the three RyR isoforms in male germ cells at different stages of maturation by western blot and RT-PCR. RyR1 was expressed in spermatogonia, pachytene spermatocytes and round spermatids whereas RyR2 was found only in 5- to 10-day-old testis but not in germ cells. RyR3 was not revealed at the protein level, although its mRNA was detected in mixed populations of germ cells. Caffeine, a known agonist of RyRs, was able to induce release of Ca(2+) from intracellular stores in spermatogonia, pachytene spermatocytes and round spermatids, but not spermatozoa. Treatment with high doses of ryanodine, which are known to block RyR channel activity, reduced spermatogonial proliferation and induced meiosis in in vitro organ cultures of testis from 7-day-old mice. In conclusion, the results presented here indicate that RyRs are present in germ cells and that calcium mobilization through RyR channels could participate to the regulation of male germ maturation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caffeine / pharmacology
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Cell Differentiation / physiology
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Developmental / physiology
  • Male
  • Meiosis / drug effects
  • Meiosis / genetics
  • Mice
  • Organ Culture Techniques
  • RNA, Messenger / metabolism
  • Ryanodine / pharmacology
  • Ryanodine Receptor Calcium Release Channel / drug effects
  • Ryanodine Receptor Calcium Release Channel / genetics
  • Ryanodine Receptor Calcium Release Channel / metabolism*
  • Spermatids / cytology
  • Spermatids / drug effects
  • Spermatids / metabolism
  • Spermatocytes / cytology
  • Spermatocytes / drug effects
  • Spermatocytes / metabolism
  • Spermatogenesis / physiology*
  • Spermatogonia / cytology
  • Spermatogonia / drug effects
  • Spermatogonia / metabolism*
  • Testis / cytology*
  • Testis / metabolism

Substances

  • RNA, Messenger
  • Ryanodine Receptor Calcium Release Channel
  • Ryanodine
  • Caffeine
  • Calcium

Grants and funding