Genomewide discovery and classification of candidate ovarian fertility genes in the mouse.
Female infertility syndromes are among the most prevalent chronic health disorders in women, but their genetic basis remains unknown because of uncertainty regarding the number and identity of ovarian factors controlling the assembly, preservation, and maturation of ovarian follicles. To systematically discover ovarian fertility genes en masse, we employed a mouse model (Foxo3) in which follicles are assembled normally but then undergo synchronous activation. We developed a microarray-based approach for the systematic discovery of tissue-specific genes and, by applying it to Foxo3 ovaries and other samples, defined a surprisingly large set of ovarian factors (n = 348, approximately 1% of the mouse genome). This set included the vast majority of known ovarian factors, 44% of which when mutated produce female sterility phenotypes, but most were novel. Comparative profiling of other tissues, including microdissected oocytes and somatic cells, revealed distinct gene classes and provided new insights into oogenesis and ovarian function, demonstrating the utility of our approach for tissue-specific gene discovery. This study will thus facilitate comprehensive analyses of follicle development, ovarian function, and female infertility.
Department of Pathology and Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9072, USA.
Teresa D
TD
Gallardo
George B
GB
John
Lane
L
Shirley
Cristina M
CM
Contreras
Esra A
EA
Akbay
J Marshall
JM
Haynie
Samuel E
SE
Ward
Meredith J
MJ
Shidler
Diego H
DH
Castrillon
D000818:Animals; D015152:Blotting, Northern; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling; D005796:Genes / Q000502:physiology*; D016678:Genome; D017403:In Situ Hybridization; D007247:Infertility, Female / Q000378:metabolism* / Q000473:pathology; D007834:Lasers; D008540:Meiosis; D008597:Menstrual Cycle; D051379:Mice; D018345:Mice, Knockout; D042282:Microdissection; D020411:Oligonucleotide Array Sequence Analysis; D009865:Oocytes / Q000502:physiology / Q000648:ultrastructure; D009866:Oogenesis / Q000502:physiology; D006080:Ovarian Follicle / Q000502:physiology* / Q000648:ultrastructure; D015347:RNA Probes; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D015347:RNA Probes; D012333:RNA, Messenger