TY - JOUR
T1 - GATA4 deficiency impairs ovarian function in adult mice
AU - Kyrönlahti, Antti
AU - Vetter, Melanie
AU - Euler, Rosemarie
AU - Bielinska, Malgorzata
AU - Jay, Patrick Y.
AU - Anttonen, Mikko
AU - Heikinheimo, Markku
AU - Wilson, David B.
PY - 2011/5
Y1 - 2011/5
N2 - Transcription factor GATA4 is expressed in granulosa cells and, to a lesser extent, in other ovarian cell types. Studies of mutant mice have shown that interactions between GATA4 and its cofactor, ZFPM2 (also termed FOG2), are required for proper development of the fetal ovary. The role of GATA4 in postnatal ovarian function, however, has remained unclear, in part because of prenatal lethality of homozygous mutations in the Gata4 gene in mice. To circumvent this limitation, we studied ovarian function in two genetically engineered mouse lines: C57BL/6 (B6) female mice heterozygous for a Gata4-null allele, and 129;B6 female mice in which Gata4 is deleted specifically in proliferating granulosa cells using the Cre-loxP recombination system and Amhr2-cre. Female B6 Gata4+/- mice had delayed puberty but normal estrous cycle lengths and litter size. Compared to wild-type mice, the ovaries of gonadotropinstimulated B6 Gata4+/- mice were significantly smaller, released fewer oocytes, produced less estrogen, and expressed less mRNA for the putative GATA4 target genes Star, Cyp11a1, and Cyp19. Gata4 conditional knockout (cKO) mice had a more severe phenotype, including impaired fertility and cystic ovarian changes. Like Gata4+/- mice, the ovaries of gonadotropinstimulated cKO mice released fewer oocytes and expressed less Cyp19 than those of control mice. Our findings, coupled with those of other investigators, support the premise that GATA4 is a key transcriptional regulator of ovarian somatic cell function in both fetal and adult mice.
AB - Transcription factor GATA4 is expressed in granulosa cells and, to a lesser extent, in other ovarian cell types. Studies of mutant mice have shown that interactions between GATA4 and its cofactor, ZFPM2 (also termed FOG2), are required for proper development of the fetal ovary. The role of GATA4 in postnatal ovarian function, however, has remained unclear, in part because of prenatal lethality of homozygous mutations in the Gata4 gene in mice. To circumvent this limitation, we studied ovarian function in two genetically engineered mouse lines: C57BL/6 (B6) female mice heterozygous for a Gata4-null allele, and 129;B6 female mice in which Gata4 is deleted specifically in proliferating granulosa cells using the Cre-loxP recombination system and Amhr2-cre. Female B6 Gata4+/- mice had delayed puberty but normal estrous cycle lengths and litter size. Compared to wild-type mice, the ovaries of gonadotropinstimulated B6 Gata4+/- mice were significantly smaller, released fewer oocytes, produced less estrogen, and expressed less mRNA for the putative GATA4 target genes Star, Cyp11a1, and Cyp19. Gata4 conditional knockout (cKO) mice had a more severe phenotype, including impaired fertility and cystic ovarian changes. Like Gata4+/- mice, the ovaries of gonadotropinstimulated cKO mice released fewer oocytes and expressed less Cyp19 than those of control mice. Our findings, coupled with those of other investigators, support the premise that GATA4 is a key transcriptional regulator of ovarian somatic cell function in both fetal and adult mice.
KW - Developmental biology
KW - Fertility
KW - Gene regulation
KW - Granulosa cells
KW - Ovary
KW - Ovulation
KW - Puberty
KW - Transcription factor
UR - http://www.scopus.com/inward/record.url?scp=79956272184&partnerID=8YFLogxK
U2 - 10.1095/biolreprod.110.086850
DO - 10.1095/biolreprod.110.086850
M3 - Article
C2 - 21248289
AN - SCOPUS:79956272184
SN - 0006-3363
VL - 84
SP - 1033
EP - 1044
JO - Biology of reproduction
JF - Biology of reproduction
IS - 5
ER -