Control of Spermatogenesis in Mice by the Cyclin D-Dependent Kinase Inhibitors p18Ink4cand p19Ink4d

• DOI: 10.1128/mcb.21.9.3244-3255.2001
• Publication Date: 2002-07-27T10:03:53Z
• Authors: Frederique Zindy; Willem den Besten; Bo Chen; Jerold E. Rehg; Esther Latres; Mariano Barbacid; Jeffrey W. Pollard; Charles J. Sherr; Paula E. Cohen; Martine F. Roussel
• Keywords: Male; 0301 basic medicine; 0303 health sciences; Cyclin-Dependent Kinase 4; Cell Cycle Proteins; Cyclin-Dependent Kinase 6; Luteinizing Hormone; Cyclin-Dependent Kinases; Mice, Inbred C57BL; Meiosis; Mice; 03 medical and health sciences; Cyclin D; Cyclins; Animals; Cyclin-Dependent Kinase Inhibitor p18; Female; Cyclin-Dependent Kinase Inhibitor p19; Enzyme Inhibitors; Follicle Stimulating Hormone; Carrier Proteins; Cyclin-Dependent Kinase Inhibitor p16; Infertility, Male

Male mice lacking both the Ink4c and Ink4d genes, which encode two inhibitors of D-type cyclin-dependent kinases (Cdks), are infertile, whereas female fecundity is unaffected. Both p18(Ink4c) p19(Ink4d) expressed in seminiferous tubules postnatal wild-type mice, being largely confined to postmitotic spermatocytes undergoing meiosis. Their combined loss associated with delayed exit spermatogonia from mitotic cell cycle, leading retarded appearance meiotic cells that do not properly differentiate instead undergo apoptosis at an increased frequency. As a result, produce few mature sperm, residual spermatozoa have reduced motility decreased viability. Whether or present, animals develop hyperplasia interstitial testicular Leydig cells, levels testosterone. The anterior pituitary fertile infertile doubly deficient for produces normal luteinizing hormone (LH). Therefore, failure testosterone secondary defects LH production, account infertility strain. By contrast, Ink4d-null double-null elevated follicle-stimulating (FSH). Because fertile, FSH production by also unlikely contribute sterility observed Ink4c/Ink4d males. Our data indicate essential male fertility. These Cdk collaborate regulating spermatogenesis, helping ensure maturation spermatocytes.