Bidirectional communication between oocytes and somatic cells 卵母细胞和体细胞的双向交流

分类:医学文献 30 0

It has long been realized that the granulose cells support oocyte development. These follicular somatic cells direct many specific oocyte functions including maintenance of the oocyte in meiotic arrest, subsequently promoting reinitiation of meiosis and nuclear maturation, and promoting oocyte competence to undergo fertilization. Recently, it has become apparent that the oocyte itself communicates directly with the granulose cells.

很早之前就有研究人员发现颗粒细胞对卵母细胞的发育有支持作用。这些卵泡体细胞调控许多特定的卵母细胞功能,包括在减数分裂阻滞时维持卵母细胞发育,之后再促进减数分裂重新启动和细胞核成熟化,以及促进卵母细胞完成受精。近期研究发现,卵母细胞与颗粒细胞明显存在直接信息交流。

There is bidirectional communication between the oocytes and the surrounding somatic cells via gap junctions and paracrine signaling, with this feedback loop facilitating the growth and development of both cell types during folliculogenesis. The oocyte actively directs a favorable microenvironment for the acquisition of its own developmental competence (1).

卵母细胞与周围体细胞之间通过缝隙连接和旁分泌信号进行双向交流,这种反馈回路促进了两种细胞类型在卵泡生成过程中的生长和发育。卵母细胞积极调控有利的微环境以促进其自身的发育(1)。

Cumulus cell expansion is a good example of this cumulus cell/oocyte interaction (1). In the peri-ovulatory period, the cumulus cells expand to form a radiating layer in response to the midcycle surge of luteinizing hormone or exogenous human chorionic gonadotropin (hCG). Cumulus expansion denotes a grade III oocyte, the optimal stage for fertilization (2). During expansion, cumulus cells secrete a hyaluronic acid-rich matrix that binds the oocyte and cumulus together, facilitates follicular extrusion and oviductal fimbrial capture, and allows sperm penetration and fertilization (3). Cumulus expansion is imperative for normal oocyte development in vivo, and oocytes not associated with cumulus expansion have limited potential for implantation (2). Expansion of the cumulus layer appears to be regulated by growth differentiation factor 9 (GDF9), an oocyte-secreted member of the transforming growth factor beta (TGFβ) superfamily, and other oocyte-secreted factors such as bone morphogenic protein 15 (BMP15) (4,5).

卵丘细胞扩张就是卵丘细胞/卵母细胞之间相互作用的一个很好的例子(1)。在排卵前期,黄体激素或外源性人绒毛膜促性腺激素(hCG)在中期突增,卵丘细胞在激素作用下扩张形成辐射层。卵丘扩张暗示了卵母细胞达到III级,是受精的最佳阶段(2)。在扩张过程中,卵丘细胞分泌富含透明质酸的基质,将卵母细胞和卵丘细胞粘合在一起,促进卵子排出和输卵管菌毛捕获卵子,使得精子能够穿透卵子并进行授精(3)。卵丘细胞扩张是卵母细胞在体内正常发育的必要条件,缺乏卵丘扩张的卵母细胞的着床潜力降低(2)。卵丘细胞的扩张似乎受到生长分化因子9(GDF9,一个由卵母细胞分泌的转化生长因子β(TGFβ)超家族的成分)和其他卵母细胞分泌的因子如骨形态发生蛋白15(BMP15)的调控(4,5)。

GDF9 induces hyaluronan synthase 2 (has2) in cumulus cells (4) stimulating the production of hyaluronic acid, which facilitates cumulus expansion (5, 6). GDF9 also facilitates cumulus expansion via the induction of cyclooxygenase 2 (PTGS2) and the resultant prostaglandin E2 (PGE2) production (7), both of which are required for cumulus expansion (8).

GDF9诱导卵丘细胞内的透明质酸合酶2(HAS2)(4)刺激产生透明质酸,从而促进卵丘扩张(5,6)。GDF9还通过诱导环氧合酶2(PTGS2)和其产物前列腺素E2(PGE2)促进卵丘扩张(7),这两种酶都是卵丘扩张的必要物质(8)。

Mice lacking functional PTGS2 have defects in ovulation, fertilization, decidualization, and implantation (9). Systemic treatment with PGE2 restores the ability of PTGS2 knock-out mice to ovulate (10). Calder et al. (8) examined expression of PTGS2 and prostaglandin receptor mRNA in bovine cumulus-oocyte complexes and found that expression of PGTS2 and EP2 mRNA is dependent on time of maturation and oocyte quality. Complexes in which the oocyte is microsurgically removed and cultured with recombinant GDF9 can be induced to undergo cumulus expansion (7).

缺乏功能性PTGS2的小鼠在排卵,受精,蜕膜和胚胎着床方面存在缺陷(9)。用PGE2进行系统性治疗可恢复PTGS2小鼠的排卵能力(10)。Colder等人(8)检测到牛的卵丘-卵母细胞复合物中PTGS2和前列腺素受体mRNA的表达,发现PGTS2和EP2 mRNA的表达取决于成熟时间和卵母细胞质量。在卵母细胞通过显微外科术移除后加入重组GDF9一起培养的环境中的复合物可以用于诱导卵丘扩张(7)。

References

参考文献

1. Matzuk MM, Burns KH, Viveiros MM, Eppig JJ. Intercellular communication in the mammalian ovary: oocytes carry the conversation. Science 2002;296:2178-80.

2. Veek L (1999). An Atlas of Human Gamates and Conceptuses. New York: Parthenon.

3. Salustri A, Camaioni A, D’Alessandris C. Endocrine and paracrine regulation of cumulus expansion. Zygote 1996;4:313-15.

4. Elvin J, Clark A, Wang P, Wolfman N, Matzuk M. Paracrine actions of growth differentiation factor-9 in the mammalian ovary. Mol Endocrinol 1999;13:1035-48.

5. Su YQ, Wu X, O’Brien MJ, et al. Synergistic roles of BMP 15 and GDF9 in the development and function of the oocyte-cumulus cell complex in mice: genetic eveidence for an oocyte-granulosa cell regulatory loop. Dev Biol 2004;276:64-73.

6. Buccione R, Vanderhyden BC, Caron PJ, Eppig JJ. FSH-induced expansion of the mouse cumulus oophorus in vitro is dependent upon a specific factor(s) secreted by the oocyte. Dev Biol 1990;167:371-8.

7. Elvin JA, Yan C, Matzuk MM. Growth differentiation factor-9 stimulates progesterone synthesis in granulose cells via a prostaglandin E2/EP2 receptor pathway. Proc Natl Acad Sci USA 2000;97:10288-93.

8. Calder MD, Caveney AN, Westhusin ME, Watson AJ. Cyclooxygenase 2 and prostaglandin E2 receptor messenger RNAs are affected by bovine oocyte maturation time and cumulus oocyte complex quality, and PGE2 induces moderate expansion of the bovine cumulus in vitro. Biol Reprod 2001.

9. Lim H, Paria BC, Das SK, et al. Multiple female reproductive failures in cyclooxygenase deficient mice. Cell 1997;91:197-208.

10. Davis BJ, Lennard DE, Lee CA, et al. Anovulation in cyclooxygenase deficient mice is restored by PGE2 and interleukin-1B. Endocrinology 1999;140:2685-95.

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