Ye Yinghui, Kawamura Kazuhiro, Sasaki Mitsue, Kawamura Nanami, Groenen Peter, Sollewijn Gelpke Maarten D, Kumagai Jin, Fukuda Jun, Tanaka Toshinobu
Department of Obstetrics and Gynecology, Akita University School of Medicine, Akita, Japan.
Reprod Biomed Online. 2009 Aug;19(2):181-90. doi: 10.1016/s1472-6483(10)60070-3.
Recent studies indicate that LH stimulates production of ovarian paracrine factors that induce meiosis of the oocyte. DNA microarray analyses of ovarian transcripts were performed in mice and major increases of a short isoform of leptin receptor, ObRa, were identified by the preovulatory LH/human chorionic gonadotrophin (HCG) surge. In oocytes, the level of ObRa transcripts was increased shortly after HCG stimulation, whereas the level of ObRb transcripts was not changed. Leptin was produced by cumulus, granulosa, theca and interstitial cells of ovaries and its transcript level was not regulated during gonadotrophin treatment. Treatment with leptin promoted germinal vesicle breakdown (GVBD) in oocytes within preovulatory follicles, and enhance first polar body extrusion in both cumulus-oocyte complexes and denuded oocytes. The leptin-promoted GVBD and first polar body extrusion were blocked by a mitogen-activated protein kinase extracellular signal regulated kinase kinases (MEK)1/2 inhibitor, U0126, but not its inactive analogue U0124. Furthermore, leptin promoted fertilization of oocytes and the in-vitro development of zygotes to preimplantation embryos. These findings suggest paracrine roles of leptin in the enhancement of nuclear maturation of oocytes through MEK1/2 signalling, and in the promotion of cytoplasmic maturation essential for successful oocyte development to the preimplantation embryos.
最近的研究表明，促黄体生成素（LH）刺激卵巢旁分泌因子的产生，从而诱导卵母细胞减数分裂。在小鼠中对卵巢转录本进行了DNA微阵列分析，通过排卵前LH/人绒毛膜促性腺激素（HCG）高峰，发现瘦素受体短异构体ObRa大幅增加。在卵母细胞中，HCG刺激后不久ObRa转录本水平升高，而ObRb转录本水平未发生变化。瘦素由卵巢的卵丘、颗粒细胞、卵泡膜细胞和间质细胞产生，其转录本水平在促性腺激素治疗期间不受调控。用瘦素处理可促进排卵前卵泡内卵母细胞的生发泡破裂（GVBD），并增强卵丘-卵母细胞复合体和裸卵中第一极体的排出。瘦素促进的GVBD和第一极体排出被丝裂原活化蛋白激酶细胞外信号调节激酶激酶（MEK）1/2抑制剂U0126阻断，但未被其无活性类似物U0124阻断。此外，瘦素促进卵母细胞受精以及受精卵体外发育为植入前胚胎。这些发现表明，瘦素通过MEK1/2信号传导在增强卵母细胞核成熟方面具有旁分泌作用，并在促进卵母细胞成功发育为植入前胚胎所必需的细胞质成熟方面发挥作用。
