Key role for cyclin-dependent kinases in the first and second meiotic divisions of rat spermatocytes

Murielle Godet1, Anne Damestoy, Sandrine Mouradian

  • 1INSERM U418/INRA UMR 1245, Hôpital Debrousse, 69322 Lyon 05, France. godet@lyon.inserm.fr

Biology of Reproduction
|December 30, 2003
PubMed

Insights

Inhibiting cyclin-dependent kinase (CDK) activity with roscovitine reduced male germ cell progression through meiosis. This demonstrates CDK

Area of Science:

  • Reproductive biology
  • Cell cycle regulation
  • Molecular endocrinology

Background:

  • The M-phase promoting factor (MPF), a complex of cdc2 (CDK1) and cyclin B1, regulates the G2/M phase transition in cell division.
  • MPF components and histone H1 kinase activity are present in pachytene spermatocytes (PS).
  • Direct inhibition of MPF activity's effect on the G2/M transition in male germ cells remains unproven.

Purpose of the Study:

  • To investigate the role of cyclin-dependent kinase (CDK) activity in male meiosis.
  • To determine if inhibiting CDK activity affects the G2/M transition in pachytene spermatocytes.
  • To establish a functional link between CDK activity and male germ cell meiotic progression.

Main Methods:

  • Coculture of pachytene spermatocytes (PS) with Sertoli cells.
  • Treatment with roscovitine, a potent inhibitor of CDK1, CDK2, and CDK5.
  • Assessment of secondary spermatocyte and round spermatid formation.
  • Measurement of cell viability.
  • Analysis of MPF levels and CDK-associated histone H1 kinase activity.

Main Results:

  • Roscovitine treatment reduced the formation of secondary spermatocytes and round spermatids without affecting cell viability.
  • The inhibitory effect of roscovitine was reversible and concentration-dependent.
  • Roscovitine did not alter MPF levels but inhibited CDK1- and CDK2-associated histone H1 kinase activity in PS.
  • The observed effects were independent of Sertoli cells.

Conclusions:

  • Cyclin-dependent kinase activity is functionally linked to the spontaneous progression of male germ cells through the first and second meiotic divisions.
  • Inhibition of CDK activity disrupts male meiosis at the G2/M transition.
  • This study provides the first evidence for the role of CDK activity in regulating the second meiotic division in male germ cells.

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