Structures of vitamin A (retinol), retinal, and major retinoic acids used in chemoprevention.
(生物谷配图)
维甲酸是维生素A的一种衍生物，有数种同分异构体，包括13顺式与全反式。
维甲酸类化合物(Retinoic acids)在调控细胞生长、分化、凋亡等生命活动中起重要作用。其在体内的生理活性代谢产物包括全反式维甲酸(ATRA)、13-顺维甲酸(13-cis-RA)和9-顺维甲酸(9-cis-RA),它们可通过核维甲酸受体(RAR)结合于DNA应答元件调节靶基因的转录;其中9-cis-RA除生物学活性较强外,尚能与维甲酸X受体(RXR)结合。
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.
(生物谷配图)
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.
(生物谷配图)
最近一期（2006年3月31日）报道美国《科学》报道， 是否存在维甲酸(Retinoic acid)决定发育中小鼠的生殖细胞最终变成卵子还是精子。 Josephine Bowles和同事的这项发现可能会给控制动物的繁殖力提供一个靶标，或是提供一种在实验室中从繁殖干细胞发育出功能卵子和精子的方法。减数分裂发生的时间决定一个发育中的生殖细胞是朝雄性还是雌性的方向发展。如果减数分裂在胚胎发育时发生，生殖细胞成为卵子。如果减数分裂被推迟到出生之后，生殖细胞则会成为精子。Bowles和同事现在显示，维甲酸引发减数分裂的开始。在雄性胚胎中，一种特有的酶降解维甲酸，从而推迟了减数细胞分裂的开始。
对于这个报道的英文权威评论如下
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.
