Intrafollicular Concentrations of the Oocyte-secreted Factors GDF9 and BMP15 Vary Inversely in Polycystic Ovaries.

Intrafollicular Concentrations of the Oocyte-secreted Factors GDF9 and BMP15 Vary Inversely in Polycystic Ovaries.
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DOI:
10.1210/clinem/dgac272
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发表时间:
2022-07-14
期刊:
The Journal of clinical endocrinology and metabolism
影响因子:
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卵母细胞分泌因子生长分化因子9(GDF 9)和骨形态发生蛋白15(BMP 15)在卵泡发育和卵母细胞成熟过程中起重要作用,其异常调控可能参与多囊卵巢综合征的发病。在患有和不患有多囊卵巢(PCO)的女性的小窦卵泡液中,GDF 9、BMP 15和GDF 9/BMP 15异源二聚体的浓度是否存在可测量的差异?卵泡液(n = 356)收集从4至11毫米的卵泡在未经刺激的卵巢的87名妇女接受卵巢组织冷冻保存生育能力。  根据年龄和卵泡大小,确定了27名PCO女性和60名无PCO样特征的女性(非PCO女性)。使用酶联免疫吸附测定法测量GDF 9、BMP 15、GDF 9/BMP 15异二聚体、抗苗勒管激素(AMH)、卵泡素-A和-B、总卵泡素、激活素-B和-AB以及卵泡抑素的卵泡内浓度。GDF 9、BMP 15和GDF 9/BMP 15异源二聚体的检出率分别为100%、94.4%和91.5%,且浓度与卵泡大小呈显著负相关(P <0.0001)。  GDF 9在患有PCO的女性中显著较高(PCO:4230 ± 189 pg/mL [平均值± SEM],n = 188;非PCO:3498 ± 199 pg/mL,n = 168; P <0.03),而BMP 15在患有PCO的女性中较低(PCO:431 ± 40 pg/mL,n = 125;非PCO:573 ± 55 pg/mL,n = 109; P = 0.10),导致患有PCO的女性中GDF 9:BMP 15比率显著较高(P <0.01)。                        在非PCO女性中,BMP 15与AMH、激活素和BMP 15之间的显著正相关在PCO女性中转为负相关。在PCO患者中,卵泡内GDF 9和BMP 15的浓度呈相反变化,反映了异常的内分泌环境。GDF 9:BMP 15比值升高可能是PCO的一种新生物标志物。
The oocyte-secreted factors growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) play essential roles in follicle development and oocyte maturation, and aberrant regulation might contribute to the pathogenesis of polycystic ovary syndrome. Are there measurable differences in concentrations of GDF9, BMP15, and the GDF9/BMP15 heterodimer in small antral follicle fluids from women with and without polycystic ovaries (PCO)? Follicle fluids (n = 356) were collected from 4- to 11-mm follicles in unstimulated ovaries of 87 women undergoing ovarian tissue cryopreservation for fertility preservation. Twenty-seven women with PCO were identified and 60 women without PCO-like characteristics (non-PCO women) were matched according to age and follicle size. Intrafollicular concentrations of GDF9, BMP15, GDF9/BMP15 heterodimer, anti-Mullerian hormone (AMH), inhibin-A and -B, total inhibin, activin-B and -AB, and follistatin were measured using enzyme-linked immunosorbent assays. The detectability of GDF9, BMP15, and the GDF9/BMP15 heterodimer were 100%, 94.4%, and 91.5%, respectively, and concentrations were significantly negatively correlated with increasing follicle size (P < 0.0001). GDF9 was significantly higher in women with PCO (PCO: 4230 ± 189 pg/mL [mean ± SEM], n = 188; non-PCO: 3498 ± 199 pg/mL, n = 168; P < 0.03), whereas BMP15 was lower in women with PCO (PCO: 431 ± 40 pg/mL, n = 125; non-PCO: 573 ± 55 pg/mL, n = 109; P = 0.10), leading to a significantly higher GDF9:BMP15 ratio in women with PCO (P < 0.01). Significant positive associations between BMP15 and AMH, activins, and inhibins in non-PCO women switched to negative associations in women with PCO. Intrafollicular concentrations of GDF9 and BMP15 varied inversely in women with PCO reflecting an aberrant endocrine environment. An increased GDF9:BMP15 ratio may be a new biomarker for PCO.
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