Human growth differentiation factor-9,GDF-9 ELISA Kit

Required for ovarian folliculogenesis. Promotes primordial follicle development. Stimulates granulosa cell proliferation. Promotes cell transition from G0/G1 to S and G2/M phases, through an increase of CCND1 and CCNE1 expression, and RB1 phosphorylation. It regulates STAR expression and cAMP-dependent progesterone release in granulosa and thecal cells. Attenuates the suppressive effects of activin A on STAR expression and progesterone production by increasing the expression of inhibin B. It suppresses FST and FSTL3 production in granulosa-lutein cells.

1. The present mini-review provides an overview of recent findings relating GDF-9 and BMP-15 as fundamental factors implicated in the regulation of ovarian function and discusses their potential role as markers of oocyte quality in women. PMID: 30039232
2. Data suggest that GDF9 and BMP15 are oocyte-secreted factors with leading roles in control of ovarian function in female reproduction, modulating both fate of somatic granulosa cells and quality/developmental competence of the egg. (GDF9 = growth and differentiation factor-9; BMP15 = bone morphogenetic protein-15) [REVIEW] PMID: 29544636
3. GDF9 single nucleotide polymorphism is not associated with Endometriosis-associated infertility. PMID: 28831646
4. GDF9 single nucleotide polymorphism is associated with fecundity. PMID: 28762037
5. Asiaticoside hindered the invasive growth of KFs by inhibiting the GDF-9/MAPK/Smad pathway. PMID: 28346732
6. Human GDF9 and BMP15 act synergistically to stimulate granulosa cell proliferation, a response that also involves species-specific non-SMAD signalling pathways. PMID: 25155366
7. these results indicated that the GDF9 C447T SNP is a possible candidate genetic risk factor for female infertility in the Polish population. PMID: 27035733
8. GDF-9 promotes the proliferation and migration of keloid fibroblasts via a mechanism involving the Smad2/3 pathway. PMID: 27855376
9. GDF9 c.169G>T (D57Y), c.546G>A (rs1049127), and BMP15 rs79377927 (788_789insTCT) were associated with premature ovarian failure in the Chinese Hui population. PMID: 25954833
10. results support a model of activation for human GDF9 dependent on cumulin formation through heterodimerization with BMP15. Oocyte-secreted cumulin is likely to be a central regulator of fertility in mono-ovular mammals. PMID: 26254468
11. GDF-9 and GDF-15 levels may influence bone parameters in polycystic ovary syndrome PMID: 24430093
12. GDF9 and BMP15 expression is reduced in primordial, primary, and secondary follicles in ovarian tissues of PCOS patients. PMID: 25172094
13. The arginine residue in the pre-helix loop of GDF9 homodimer may prevent the inhibition from its pro-domain or directly alter receptor binding, but this residue in GDF9 does not significantly affect the heterodimer activity. PMID: 25253739
14. Eleven unique copy number changes are identified in a total of 11 patients, including a tandem duplication of 475 bp, containing part of the GDF9 gene promoter region. PMID: 24939957
15. Data suggest up-regulation of mRNA for GDF9 and BMP15 (bone morphogenetic protein 15) in cumulus granulosa cells serves as biomarker for oocyte maturation, fertilization, embryo quality, and pregnancy in couples undergoing ICSI for male infertility. PMID: 25139161
16. These results suggest that COCs cultured with recombinant GDF9 in oocyte maturation medium improve oocyte developmental competence and subsequent developmental competence of cloned embryo in cattle. PMID: 24840335
17. Reduced expression of growth and differentiation factor-9 is associated with aggressive behaviour of clear-cell renal cell carcinoma. PMID: 25368253
18. Oocyte-derived GDF9 does not alter gap junction intercellular communication activity between human granulosa cells. PMID: 24413384
19. Alterations to hGDF9 synthesis and activity can contribute to the most common ovarian pathologies. PMID: 24438375
20. genetic association studies in population of Han women in China: Data suggest that a mutation in precursor region of GDF9 (R146C) is associated with premature ovarian failure (POF); R146C mutation found in 3 women with POF but absent in controls. PMID: 23851219
21. FOXL2 expression is required for GDF-9 stimulation of follistatin transcription. PMID: 23523567
22. BMP15 and GDF9 transcript levels increase in mature oocytes from women with polycystic ovary syndrome after ovarian stimulation, and might inhibit the progesterone secretion by follicular cells PMID: 22825968
23. findings that GDF9:BMP15 heterodimers are the most bioactive ligands in mice and humans compared with homodimers explain many puzzling genetic and physiological data and have important implications for improving female fertility in mammals PMID: 23382188
24. CDC6 and GDF-9 might be closely related to the carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma. PMID: 23011157
25. It was shown that human kidney tumours have a reduced or loss of expression of GDF9. In vitro, GDF9 overexpression suppresses the invasiveness, growth and migration of kidney cancer cells. PMID: 23060562
26. GDF-9 levels are inversely correlated with the growth, adhesion and migration of bladder cancer cells in vitro. PMID: 22159313
27. GDF9 may contribute to the variation observed in follicular development, ovulation rate, and fecundity between mammals PMID: 22234469
28. GDF9 decreases basal and activin A-induced FST and FSTL3 expression, and this explains, in part, its enhancing effects on activin A-induced inhibin beta(B)-subunit mRNA expression and inhibin B production in hGL cells PMID: 21829661
29. In the samples from girls/women, the number of developing follicles was greater with GDF9 or BMP15 alone than with no BMP15 or GDF9. PMID: 21632818
30. The expression of GDF9 and BMP15 in oocytes from patients with polycystic ovary syndrome cannot reach the normal level even after ovarian stimulation. PMID: 21669410
31. Higher mature GDF9 levels in the follicular fluid were significantly correlated with oocyte nuclear maturation and embryo quality. PMID: 21496799
32. GDF-9 signaling via ALK-5, can promote cell invasiveness PMID: 21116689
33. Integral role of GDF-9 and BMP-15 in ovarian function. PMID: 21226076
34. GDF-9 can promote the motile and adhesive capacity of PC-3 prostate cancer cells by up-regulating expression of FAK and paxillin in a Smad dependent manner, suggesting a pro-tumourigenic role for GDF-9 in prostate cancer. PMID: 21042764
35. Impaired production of BMP15 and GDF9 mature proteins derived from proproteins with mutation in the proregion. PMID: 20547206
36. Mutational analysis of the coding region of GDF9 among 216 Chinese polycystic ovary syndrome patients. Five novel missense mutations were discovered namely c.15C>G, c.118T>G, c.133A>G, c.1025A>T and c.1275C>A. PMID: 20705511
37. The detection of GDF9 and TGFbetaR1 at both at the protein and mRNA levels suggests that GDF9 may have functions in human preantral follicles. PMID: 20427239
38. GDF-9 c.G546A, but not c.G169A or c.C447T, is correlated with the poor ovarian stimulation and in vitro fertilization outcomes in women with diminished ovarian reserve. PMID: 20451184
39. GDF9 attenuates the suppressive effects of activin A on StAR expression and progesterone production by increasing the expression of inhibin B, which acts as an activin A competitor. PMID: 20660033
40. Cell growth was significantly increased in the GDF9 over-expressing cells compared to the two controls; apoptosis was decreased in the presence of GDF9. PMID: 20458753
41. GDF-9 concentration in women with severe endometriosis was lower than in those without PMID: 19931079
42. data demonstrate that polymorphisms in major folliculogenesis genes, GDF9, BMP15, AMH, and AMHR2, are not associated with polycystic ovary syndrome susceptibility. PMID: 20236105
43. Reduced GDF-9 expression in cumulus granulosa cells of patients with polycystic ovary syndrome (PCOS) appears to be associated with decreased long-term developmental potential of the oocytes of patients with PCOS. PMID: 19376510
44. Data show that Golgi apparatus casein kinase (G-CK) catalyzes the phosphorylation of rhBMP-15 and rhGDF-9. PMID: 20067794
45. 2 synonymous mutations (c.447C>T, c.546G>A) & a novel missense variant (c.169G>T) were found in both premature ovarian failure patients & control subjects in the coding region of GDF9, indicating them as a novel polymorphism PMID: 19438907
46. Bone morphogenetic protein receptor type II is a receptor for growth differentiation factor-9 PMID: 12135884
47. interaction with bone morphogenetic protein-15 PMID: 12446716
48. BMP-15 and GDF-9 have roles in fertility; critical sequences are determined by mutagenesis PMID: 14970198
49. This case-control study revealed eight mutations in the GDF9 gene in women with premature ovarian failure PMID: 16278619
50. although mutations in BMP15 and GDF9 are not a major cause of ovarian insufficiency, they may be involved in premature ovarian failure PMID: 16645022

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Altered GDF9 function may be involved in ovarian disorders. Rare variants in GDF9 have been found in patients with premature ovarian failure and mothers of dizygotic twins.

Secreted.

TGF-beta family

Expressed in ovarian granulosa cells. Present in oocytes of primary follicles (at protein level).

HGNC: 4224

OMIM: 601918

KEGG: hsa:2661

STRING: 9606.ENSP00000296875

UniGene: Hs.25022