GATA4 regulates Sertoli cell function and fertility in adult male mice

被引：101

作者：

Kyroenlahti, Antti ^{[5
]}

Euler, Rosemarie ^{[6
]}

Bielinska, Malgorzata

Schoeller, Erica L. ^{[3
]}

Moley, Kelle H. ^{[3
,4
]}

Toppari, Jorma ^{[7
,8
]}

Heikinheimo, Markku ^{[5
]}

Wilson, David B. ^{[1
,2
]}

机构：

[1] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA

[2] Washington Univ, Dept Dev Biol, St Louis, MO 63110 USA

[3] Washington Univ, Dept Obstet & Gynecol, St Louis, MO 63110 USA

[4] Washington Univ, Dept Cell Biol & Physiol, St Louis, MO 63110 USA

[5] Univ Helsinki, Biomedicum Helsinki, Childrens Hosp, FIN-00290 Helsinki, Finland

[6] Univ Appl Sci, Hsch Mannheim, D-68163 Mannheim, Germany

[7] Univ Turku, Dept Physiol, Turku, Finland

[8] Univ Turku, Dept Pediat, Turku, Finland

来源：

MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2011年 / 333卷 / 01期

基金：

芬兰科学院;

关键词：

Infertility; Spermatogenesis; Testis; Transcription factor; TRANSCRIPTION FACTOR GATA-4; NECROSIS-FACTOR-ALPHA; HEART TUBE FORMATION; MOUSE SPERMATOGENESIS; GENE-EXPRESSION; VENTRAL MORPHOGENESIS; OVARIAN DEVELOPMENT; ANDROGEN RECEPTOR; SEX DETERMINATION; GONADAL-FUNCTION;

D O I：

10.1016/j.mce.2010.12.019

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

引用

页码：85 / 95

页数：11

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