ovarian stem cell marker////Marker genes identify three somatic cell types in the fetal mouse ovary. Rastetter RH et al. (2014) The two main functions of the ovary are the production of oocytes, which allows the continuation of the species, and secretion of female sex hormones, which control many aspects of female development and physiology. Normal development of the ovaries during embryogenesis is critical for their function and the health of the individual in later life. Although the adult ovary has been investigated in great detail, we are only starting to understand the cellular and molecular biology of early ovarian development. Here we show that the adult stem cell marker Lgr5 is expressed in the cortical region of the fetal ovary and this expression is mutually exclusive to FOXL2. Strikingly, a third somatic cell population can be identified, marked by the expression of NR2F2, which is expressed in LGR5- and FOXL2 double-negative ovarian somatic cells. Together, these three marker genes label distinct ovarian somatic cell types. Using lineage tracing in mice, we show that Lgr5-positive cells give rise to adult cortical granulosa cells, which form the follicles of the definitive reserve. Moreover, LGR5 is required for correct timing of germ cell differentiation as evidenced by a delay of entry into meiosis in Lgr5 loss-of-function mutants, demonstrating a key role for LGR5 in the differentiation of pre-granulosa cells, which ensure the differentiation of oogonia, the formation of the definitive follicle reserve, and long-term female fertility.//////////////////
Chicken ovalbumin upstream promoter transcription factors (COUP-TFs) are members of the steroid/thyroid hormone receptor superfamily. They are often called orphan receptors, since their ligands have not been identified. COUP-TF homologs have been cloned in many species, from Drosophila to human. The protein sequences are highly homologous across species, suggesting functional conservation. ARP1, also called COUP-TFII, and COUP-TFI (132890), were cloned from the human and their genomic organization characterized.
NCBI Summary:
This gene encodes a member of the steroid thyroid hormone superfamily of nuclear receptors. The encoded protein is a ligand inducible transcription factor that is involved in the regulation of many different genes. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]
General function
DNA binding, Transcription factor
Comment
Cellular localization
Nuclear
Comment
Ovarian function
Follicle development, Steroid metabolism
Comment
Expression regulated by
Comment
Ovarian localization
Theca
Comment
Sato Y, et al 2003 reported immunolocalization of Nuclear Transcription Factors, DAX-1 and COUP-TF
II, in the Normal Human Ovary and Correlation with Adrenal 4 Binding Protein/
Steroidogenic Factor-1 Immunolocalization during the Menstrual Cycle.
Steroid synthesis in the human ovary is regulated by the temporal and spatial expression of enzymes
involved in each step of ovarian steroidogenesis. Recent studies have demonstrated that DAX-1 and
COUP-TFII negatively regulate adrenal 4 binding protein (Ad4BP)/steroidogenic factor-1
(SF-1)-dependent transcription of steroidogenic enzymes in experimental animals. In this study the
expression patterns of these proteins in human normal ovaries were examined using
immunohistochemistry and compared with those of steroidogenic enzymes. In the ovarian follicle
and corpora lutea, immunoreactive DAX-1 protein was detected predominantly in granulosa cells,
whereas COUP-TFII was identified in thecal cells. In granulosa cells, both immunoreactive DAX-1
and Ad4BP/SF-1 protein expression increased after the preantral follicular stage. DAX-1
immunoreactivity was relatively high compared with that of Ad4BP/SF-1 in all follicular stages
from premordial to nondominant. The increase in expression of Ad4BP/SF-1 immunoreactivity
between follicles in the preantral and dominant stages of follicular development was greater than
that in DAX-1 expression. In thecal cells, immunoreactive COUP-TFII was consistently elevated
throughout the menstrual cycle, whereas Ad4BP/SF-1 immunoreactivity increased according to the
development of the follicle. These results indicated that DAX-1 and COUP-TFII may play a role in
the modulation of Ad4BP/SF-1-dependent transcription of steroidogenic enzymes in different cell
types and follicular stages in normal cycling human ovaries.
Follicle stages
Comment
Involvement of Ad4BP/SF-1, DAX-1, and COUP-TFII transcription factor on steroid production and luteinization in ovarian theca cells. Murayama C et al. To examine the essential mechanisms of steroid production in ovarian theca cells, we analyzed the expression of genes associated with steroid production using simple culture system with serum medium. In addition, we examined the involvement of DAX-1, COUP-TFII, and Ad4BP/SF-1 transcription factors on the steroid production in theca cells. Theca cells begin to display an elongated or fibroblastic aspect within 24 h of culture. Over the next 48 h, they metamorphosed from the fibroblastic to the epitheloid phenotype. The number of theca cells increased during culture period. Androstenedione and progesterone production per cell decreased at 48-96 h compared with 0-48 h of culture. Steroidogenic acute regulatory protein (StAR) and CYP 17 genes expression decreased at 48 h compared with 0 h of culture, and afterward maintained a low level. In contrast, expression of 3beta-HSD and P450scc mRNAs increased at 48 h compared with 0 h of culture. Protein expression of Ab4BP/SF-1 maintained a constant level during culture. COUP-TFII protein expression showed a peak level at 24 h of culture period. DAX-1 protein expression began to increase at 48 h of culture. Our data suggested that the inhibition in CYP 17 and StAR genes by DAX-1 transcription factor may be associated with the decrease in androstenedione and progesterone production by theca cells during in vitro culture. Such an essential pathway for steroid production might indicate the importance of theca cell function in bovine ovary.
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: subfertile Comment: Haploinsufficiency of COUP-TFII in Female Reproduction Takamoto N, et al .
The chicken ovalbumin upstream promoter transcription factor II, COUP-TFII, is a member of the Orphan nuclear receptor transcription factor family. Genetic ablation of COUP-TFII results in early embryonic lethality and demonstrates that this gene is required for cardiac and vascular development. Expression of COUP-TFII persists throughout postnatal life in various tissues including the female reproductive tract. However, the physiological function of COUP-TFII in female reproduction has not been extensively analyzed. Here, we provide phenotypic evidences that haploinsufficiency of COUP-TFII in mice demonstrates an important role of COUP-TFII for normal female reproduction. COUP-TFII +/- females show significantly reduced fecundity, irregular estrus cycles, delayed puberty and retarded postnatal growth. Analysis of the reduced fertility revealed that although ovarian function was normal with respect to ovulation, the ovaries have reduced ability to synthesize progesterone in response to exogenous gonadotropins. This reduction is due to the reduction of the expression of steroidogenic enzymes important for P4 synthesis and the reduction of vascularization in COUP-TFII heterozygotes. Analysis of uterine function demonstrated a reduced response to an experimentally induced decidual cell reaction indicating that the ability of the uterus to support embryo implantation was reduced. Taken together, our data shows global impact of gene dosage effects of COUP-TFII on female postnatal life and indicates requirement of COUP-TFII in normal female reproduction, in particular for uterine endometrial functions during the peri-implantation period.