Structures of vitamin A (retinol), retinal, and major retinoic acids used in chemoprevention.
(生物谷配圖)
維甲酸是維生素A的一種衍生物,，有數(shù)種同分異構體,，包括13順式與全反式,。
維甲酸類化合物(Retinoic acids)在調控細胞生長,、分化,、凋亡等生命活動中起重要作用,。其在體內的生理活性代謝產物包括全反式維甲酸(ATRA),、13-順維甲酸(13-cis-RA)和9-順維甲酸(9-cis-RA),它們可通過核維甲酸受體(RAR)結合于DNA應答元件調節(jié)靶基因的轉錄;其中9-cis-RA除生物學活性較強外,尚能與維甲酸X受體(RXR)結合,。
Animal Meiosis
Fifteen stages illustrate the reduction, division, which takes place within the sex organs of a typical animal, resulting in haploid germ cells. For simplicity, only three chromosomes are depicted.
(生物谷配圖)
Animal Mitosis
Nine key stages in nuclear and cell division in a typical animal. For the sake of clarity, only four pairs of chromosomes are represented.
(生物谷配圖)
最近一期（2006年3月31日）報道美國《科學》報道,， 是否存在維甲酸(Retinoic acid)決定發(fā)育中小鼠的生殖細胞最終變成卵子還是精子,。 Josephine Bowles和同事的這項發(fā)現(xiàn)可能會給控制動物的繁殖力提供一個靶標，或是提供一種在實驗室中從繁殖干細胞發(fā)育出功能卵子和精子的方法,。減數(shù)分裂發(fā)生的時間決定一個發(fā)育中的生殖細胞是朝雄性還是雌性的方向發(fā)展,。如果減數(shù)分裂在胚胎發(fā)育時發(fā)生,，生殖細胞成為卵子。如果減數(shù)分裂被推遲到出生之后,，生殖細胞則會成為精子,。Bowles和同事現(xiàn)在顯示，維甲酸引發(fā)減數(shù)分裂的開始,。在雄性胚胎中,，一種特有的酶降解維甲酸，從而推遲了減數(shù)細胞分裂的開始,。
對于這個報道的英文權威評論如下
Retinoic acid may control germ cells
Studies in Science and PNAS may overturn dogma of genetically programmed fates for gonadal cells
[Published 31st March 2006 06:33 PM GMT]
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Retinoic acid appears to control the timing and perhaps the choice for germ cells in the developing mouse to begin changing into eggs or sperm, scientists report in the March 30 online edition of Science. Their paper, and the recent findings of another group appearing in the Proceedings of the National Academy of Sciences, could force a rethinking of prevailing theories that suggest germ cells have genetically programmed fates.
Instead, germ cells may be "a blank slate that await chemical instructions to tell them which way to go," Science study coauthor Peter Koopman at the University of Queensland in Brisbane told The Scientist.
Whether developing germ cells become male or female depends on when they enter meiosis. If meiosis begins during fetal development, oogenesis is triggered, while delayed meiosis spurs spermatogenesis. It is widely thought that fetal germ cells in both males and females are intrinsically programmed to enter meiosis and trigger oogenesis unless prevented from doing so by a meiosis-inhibiting factor in males that until now had not been identified, Koopman said.
Koopman and his colleagues screened for genes expressed in a sex-specific manner during mouse gonadogenesis and focused on Cyp26b1, the product of which degrades retinoic acid, which in turn regulates the development of many organ systems. Quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis showed that expression of the gene became male-specific about 12.5 days post coitum.
Koopman and his colleagues found that in male Cyp26b1-knockout mice, germ cells enter meiosis precociously, suggesting CYP26B1 is the meiosis-inhibiting factor in male embryos. The PNAS study similarly found Cyp26b1 is expressed in embryonic mouse testes but not in ovaries, and that an inhibitor of CYP26 enzymes induced expression of pre-meiotic marker Stra8 in the testes. CYP26B1 is the only CYP26 enzyme found in embryonic gonads.
In quantitative RT-PCR experiments, Koopman and his colleagues found exposing male urogenital ridge organ cultures to retinoic acid induced the expression of Stra8 and meiotic progression markers Scp3 and Dmc1, while suppressing the pluripotency marker Oct4. Exposing female urogenital ridge organ cultures to a retinoic acid receptor antagonist prevented the downregulation of Oct4 normally observed in fetal ovaries and substantially decreased Stra8, Scp3 and Dmc1 expression, suggesting retinoic acid is a meiosis-inducing factor. The PNAS study likewise found retinoic acid stimulated Stra8 expression in embryonic mouse testes.
"They have certainly made an important observation in terms of an area of cell cycle control about which we know little, the trigger for entry into meiosis. Being able to putatively identify a signaling pathway we can now begin to dissect is very exciting," Debra Wolgemuth at Columbia University in New York, who did not participate in either study, told The Scientist.
Still, "a lot more research needs to be done to show whether or not the fate of these cells has actually been changed," Wolgemuth cautioned. Experiments should test whether germ cells in males that precociously enter meiosis express male- or female-specific proteins, she said.
William Blaner at Columbia University, who did not participate in either study, suggested future experiments could also examine the expression patterns of enzymes upstream of retinoic acid synthesis to see if they help regulate germ cell meiosis as well and analyze whether the byproducts of CYP26B1's metabolism of retinoic acid act on germ cells too. PNAS study coauthor Michael Griswold at Washington State University in Pullman added that he is analyzing what role retinoic acid plays in spermatogenesis in mice after birth.
