Genomewide Discovery and Classification of Candidate Ovarian Fertility Genes in the Mouse

Abstract

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 ¼ 348, $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.

PAX7 expression defines germline stem cells in the adult testis

“…RNA preparation, microarray hybridization, normalization, quality control, and digital Northern analysis was performed as described previously (24). Additional data sets included in this analysis were intact PD2 testes and cultured SSCs established as previously described (61), both from FVB/n mice.…”

Lkb1inactivation is sufficient to drive endometrial cancers that are aggressive yet highly responsive to mTOR inhibitor monotherapy

“…Having successfully employed this method for the systematic discovery of ovary-specific fertility factors (Gallardo et al, 2007b), we then applied the method to the mouse uterus, leading to the identification of five candidate genes. Subsequent analyses demonstrated that one of these genes, Sprr2f, was highly expressed in the uterus, but not in other tissues (Fig.…”

“…To identify uterine-specific genes in the mouse, mouse uteri harvested on the day of estrus, and a panel of 13 other tissues, were profiled using Affymetrix 430 2.0 arrays exactly as described (Gallardo et al, 2007b). All data sets were normalized by global scaling, and each probe set in the array was ranked by the signal ratio of the uterine sample relative to the average of the 13 somatic tissues.…”

Screening of genes involved in chromosome segregation during meiosis I: in vitro gene transfer to mouse fetal oocytes

“…[20][21][22][23] Although gene expression profile data for fetal or neonatal ovaries have been provided in mouse and human, and have enabled the analysis of genes involved in the initiation of meiosis, the sex differentiation of the gonad, early meiosis, and ovarian and follicle development, investigations of meiotic prophase I have been lacking. [24][25][26][27][28] In yeast, it is estimated that B150 genes may be meiosis-specific. 29,30 In our current study, we screened 99 genes that are upregulated during prophase in meiosis I.…”