TY - JOUR
T1 - GATA4 regulates Sertoli cell function and fertility in adult male mice
AU - Kyrönlahti, Antti
AU - Euler, Rosemarie
AU - Bielinska, Malgorzata
AU - Schoeller, Erica L.
AU - Moley, Kelle H.
AU - Toppari, Jorma
AU - Heikinheimo, Markku
AU - Wilson, David B.
PY - 2011/2/10
Y1 - 2011/2/10
N2 - 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.
AB - 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.
KW - Infertility
KW - Spermatogenesis
KW - Testis
KW - Transcription factor
UR - http://www.scopus.com/inward/record.url?scp=78651451766&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2010.12.019
DO - 10.1016/j.mce.2010.12.019
M3 - Article
C2 - 21172404
AN - SCOPUS:78651451766
SN - 0303-7207
VL - 333
SP - 85
EP - 95
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1
ER -