title: GATA4 regulates Sertoli cell function and fertility in adult male mice.
abstract: Transcription factor GATA4 is expressed in Sertoli and Leydig cells and is required for proper development of the murine fetal testis. The role of GATA4 in adult testicular function, however, has remained unclear due to prenatal lethality of mice harboring homozygous mutations in Gata4. To characterize the function of GATA4 in the adult testis, we generated mice in which Gata4 was conditionally deleted in Sertoli cells using Cre-LoxP recombination with Amhr2-Cre. Conditional knockout (cKO) mice developed age-dependent testicular atrophy and loss of fertility, which coincided with decreases in the quantity and motility of sperm. Histological analysis demonstrated Sertoli cell vacuolation, impaired spermatogenesis, and increased permeability of the blood-testis barrier. RT-PCR analysis of cKO testes showed decreased expression of germ cell markers and increased expression of testicular injury markers. Our findings support the premise that GATA4 is a key transcriptional regulator of Sertoli cell function in adult mice.
authors.affiliation: Department of Pediatrics, Washington University, St. Louis, MO 63110, USA.
authors.forename: Antti
authors.initials: A
authors.lastname: Kyrönlahti
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Euler
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Bielinska
authors.forename: Erica L
authors.initials: EL
authors.lastname: Schoeller
authors.forename: Kelle H
authors.initials: KH
authors.lastname: Moley
authors.forename: Jorma
authors.initials: J
authors.lastname: Toppari
authors.forename: Markku
authors.initials: M
authors.lastname: Heikinheimo
authors.forename: David B
authors.initials: DB
authors.lastname: Wilson
mesh_terms: D000375:Aging; D000818:Animals; D001284:Atrophy; D005298:Fertility / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering; D012708:Sertoli Cells / Q000378:metabolism*; D013081:Sperm Motility / Q000502:physiology; D013091:Spermatogenesis; D013737:Testis / Q000196:embryology / Q000473:pathology
chemical_list: D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D034741:RNA, Small Interfering