Neurotrophins initiate their biological effects by binding to cell
membrane tyrosine kinase receptors of the trk protooncogene family. In addition,
all neurotrophins recognize with similar affinity a different receptor molecule
known as p75 nerve growth factor receptor (p75 NGFR) or low affinity NGFR,
which appears to interact with the trk receptors to potentiate their response to
neurotrophins.
Using a
yeast 2-hybrid screen with the cytosolic domain of p75(NTR) as bait, Mukai et al. (2000) obtained cDNAs encoding
mouse and human p75(NTR)-associated cell death executor, or NADE. Human NADE is identical to the the HGR74
cDNA cloned by Rapp et al. (1990) from an ovarian granulosa cDNA library. HGR74 was expressed in testis, prostate,
seminal vesicle, and ovarian granulosa cells.
NCBI Summary:
Expressed in testis, prostate, seminal vesicle, and ovarian granulosa cells
General function
Receptor, Cell death/survival, Apoptosis
Comment
Cellular localization
Other Membrane
Comment
Ovarian function
Follicle endowment, Follicle development, Follicle atresia, Early embryo development
Comment
Ovarian brain-derived neurotrophic factor (BDNF) promotes the development of oocytes into preimplantation embryos Kawamura K, et al .
Optimal development of fertilized eggs into preimplantation embryos is essential for reproduction. Although mammalian oocytes ovulated after luteinizing hormone (LH) stimulation can be fertilized and promoted into early embryos in vitro, little is known about ovarian factors important for the conditioning of eggs for early embryo development. Because LH interacts only with ovarian somatic cells, its potential regulation of oocyte functions is presumably mediated by local paracrine factors. We performed DNA microarray analyses of ovarian transcripts and identified brain-derived neurotrophic factor (BDNF) secreted by granulosa and cumulus cells as an ovarian factor stimulated by the preovulatory LH surge. Ovarian BDNF acts on TrkB receptors expressed exclusively in oocytes to enhance first polar body extrusion of oocytes and to promote the in vitro development of zygotes into preimplantation embryos. Furthermore, in vivo treatment with a Trk receptor inhibitor suppressed first polar body extrusion and the progression of zygotes into blastocysts. Thus, ovarian BDNF is important to nuclear and cytoplasmic maturation of the oocyte, which is essential for successful oocyte development into preimplantation embryos. Treatment with BDNF could condition the cultured oocytes for optimal progression into the totipotent blastocysts.
Expression regulated by
Growth Factors/ cytokines, TNF
Comment
Mural granulosa cell gene expression associated with oocyte developmental competence. Jiang JY et al. ABSTRACT: BACKGROUND: Ovarian follicle development is a complex process. Paracrine interactions between somatic and germ cells are critical for normal follicular development and oocyte maturation. Studies have suggested that the health and function of the granulosa and cumulus cells may be reflective of the health status of the enclosed oocyte. The objective of the present study is to assess, using an in vivo immature rat model, gene expression profile in granulosa cells, which may be linked to the developmental competence of the oocyte. We hypothesized that expression of specific genes in granulosa cells may be correlated with the developmental competence of the oocyte. METHODS: Immature rats were injected with eCG and 24h thereafter with anti-eCG antibody to induce follicular atresia or with pre-immune serum to stimulate follicle development. A high percentage (30-50%, normal developmental competence, NDC) of oocytes from eCG/pre-immune serum group developed to term after embryo transfer compared to those from eCG/anti-eCG (0%, poor developmental competence, PDC). Gene expression profiles of mural granulosa cells from the above oocyte-collected follicles were assessed by Affymetrix rat whole genome array. RESULTS: The result showed that twelve genes were up-regulated, while one gene was down-regulated more than 1.5 folds in the NDC group compared with those in the PDC group. Gene ontology classification showed that the up-regulated genes included lysyl oxidase (Lox) and nerve growth factor receptor associated protein 1 (Ngfrap1), which are important in the regulation of protein-lysine 6-oxidase activity, and in apoptosis induction, respectively. The down-regulated genes included glycoprotein-4-beta galactosyltransferase 2 (Ggbt2), which is involved in the regulation of extracellular matrix organization and biogenesis. CONCLUSIONS: The data in the present study demonstrate a close association between specific gene expression in mural granulosa cells and the developmental competence of oocytes. This finding suggests that the most differentially expressed gene, lysyl oxidase, may be a candidate biomarker of oocyte health and useful for the selection of good quality oocytes for assisted reproduction.
Ovarian localization
Granulosa
Comment
Dissen GA, et al 1995 reported the expression of neurotrophins and their receptors in the
mammalian ovary is developmentally regulated and changes at the
time of folliculogenesis.
The mature mammalian ovary has been shown to synthesize several
neurotrophins, including nerve growth factor (NGF), neurotrophin 3 (NT-3), and
neurotrophin 4/5 (NT-4/5). The ovary also expresses some of the neurotrophin
receptors, including p75 NGFR, trkB [the receptor for NT-4/5 and brain-derived
neurotropic factor (BDNF)], and trkA (the NGF receptor). The present
experiments were undertaken to determine whether neurotrophins and their
receptors are expressed at the time of definitive ovarian histogenesis, and whether
any of them exhibit a developmental pattern of expression related to the
completion of folliculogenesis. Immunohistochemical identification of p75 NGFR
in rat embryonic ovaries revealed that the receptor is predominantly expressed in
mesenchymal cells. By gestational day 18, these cells have formed pockets that
enclose presumptive pregranulosa cells and groups of oocytes into ovigerous
cords. Immediately after birth, the ovigerous cords are subdivided, resulting in the
abrupt formation of primordial follicles between 24-48 h after birth. Consistent
with these observations, the p75 NGFR messenger RNA (mRNA) content
increased after birth and remained elevated at the time of follicular assembly.