Neurotrophin NT3 promotes ovarian primordial to primary follicle transition.
Neurotrophin NT3 promotes ovarian primordial to primary follicle transition.
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DOI：
10.1530/rep-09-0179
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发表时间：
2009-10
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影响因子：
--
通讯作者：
Skinner MK
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文献类型：
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作者：
Nilsson E;Dole G;Skinner MK
神经营养素是已知在促进细胞存活和分化方面发挥作用的生长因子。当前研究的重点是检查神经营养素在调节卵巢原始卵泡发育中的作用。将 4 天龄大鼠的卵巢放入器官培养物中，在不存在或存在神经营养素 3 (NT3)、脑源性神经营养因子 (BDNF) 或神经生长因子 (NGF) 的情况下培养 10 天。用 NT3 治疗卵巢导致原始卵泡发育（即原始卵泡向初级卵泡转变）显着增加（P<0.01）。高剂量 100-250 ng/ml BDNF 治疗也显着（P<0.01）增加原始卵泡发育，但 NGF 没有效果。免疫组织化学研究确定 NT3 存在于颗粒细胞、间质组织以及原始卵泡和初级卵泡的卵母细胞中。 NT3 受体 NTRK3 存在于所有发育阶段的卵母细胞中。对主要含有原始卵泡的卵巢的分析表明，NT3、NTRK3、NGF 和 BDNF/neurotropin-4 (NT4) 受体 NTRK2 的转录本有所表达，而 BDNF、NT4 和 NGF 受体 NTRK1 则未检测到。用酪氨酸磷酸酶 AG 879 抑制 NTRK3 受体会导致卵母细胞死亡和卵泡池大小显着减少 (P<0.01)。用 K252a 抑制 NTRK 受体可减缓原始卵泡向初级卵泡的转变。微阵列分析表明，NT3处理后少数基因出现差异表达。观察结果表明，神经营养蛋白 NT3 通过卵母细胞中的 NTRK3 受体发挥作用，促进原始卵泡向初级卵泡的转变。
Neurotrophins are growth factors that are known to have a role in promoting cell survival and differentiation. The focus of the current study is to examine the role of neurotrophins in regulating ovarian primordial follicle development. Ovaries from 4-day old rats were placed into organ culture and cultured for 10 days in the absence or presence of neurotrophin-3 (NT3), brain-derived neurotrophic factor (BDNF), or nerve growth factor (NGF). Treatment of ovaries with NT3 resulted in a significant (P<0.01) increase in primordial follicle development (i.e. primordial to primary follicle transition). Treatment with BDNF at high doses of 100–250 ng/ml also significantly (P<0.01) increased primordial follicle development, but NGF had no effect. Immunohistochemical studies determined that NT3 was present in granulosa cells, interstitial tissue, and in the oocytes of primordial and primary follicles. The NT3 receptor NTRK3 was present in oocytes at all stages of development. Analysis of ovaries that contain predominantly primordial follicles demonstrated the transcripts for NT3, NTRK3, NGF, and the BDNF/neurotrophin-4 (NT4) receptor NTRK2 are expressed, while BDNF, NT4, and the NGF receptor NTRK1 are not detectable. Inhibition of the NTRK3 receptor with the tyrphostin AG 879 resulted in oocyte death and a significant (P<0.01) reduction in follicle pool size. Inhibition of the NTRK receptors with K252a slowed primordial to primary follicle transition. A microarray analysis demonstrated that a small number of genes were differentially expressed after NT3 treatment. Observations indicate that the neurotrophin NT3, acting through the NTRK3 receptor in oocytes, promotes the primordial to primary follicle transition.