抑制视黄酸生物合成能否作为一种非激素女性避孕药？
Can inhibition of retinoic acid biosynthesis function as a non-hormonal female contraceptive?
作者信息
Paik Jisun, Treuting Piper M, Haenisch Michael, Amory John K
机构信息
Department of Comparative Medicine, University of Washington, Seattle, WA, USA.
Department of Comparative Medicine, University of Washington, Seattle, WA, USA.
出版信息
Contraception. 2018 Apr 7. doi: 10.1016/j.contraception.2018.03.035.
Abstract
OBJECTIVE
Vitamin A deficient females have reduced fertility due to decreased retinoic acid production. WIN 18,446 inhibits retinoic acid biosynthesis and functions as a contraceptive in males. We tested whether WIN 18,446 treatment would suppress fertility in female mice.
STUDY DESIGN
Female mice were treated with WIN 18,446 and mated. Pregnancy rates were compared using Fisher's exact test.
RESULTS
WIN 18,446 reduced pregnancy compared with control (p=.03). However, one animal became pregnant with malformed embryos.
CONCLUSIONS
WIN 18,446 treatment significantly reduces fecundity, but teratogenicity in the setting of contraceptive failure limits the appeal of this approach to female contraception.
摘要
目的
维生素A缺乏的雌性动物由于视黄酸生成减少而生育能力降低。WIN 18,446抑制视黄酸生物合成，在雄性动物中起避孕药的作用。我们测试了WIN 18,446处理是否会抑制雌性小鼠的生育能力。
研究设计
用WIN 18,446处理雌性小鼠并使其交配。使用Fisher精确检验比较妊娠率。
结果
与对照组相比，WIN 18,446降低了妊娠率（p = 0.03）。然而，有一只动物产下了畸形胚胎。
结论
WIN 18,446处理显著降低了生育力，但避孕失败时的致畸性限制了这种女性避孕方法的吸引力。
相似文献
1
Can inhibition of retinoic acid biosynthesis function as a non-hormonal female contraceptive?抑制视黄酸生物合成能否作为一种非激素女性避孕药？
Contraception. 2018 Apr 7. doi: 10.1016/j.contraception.2018.03.035.
2
Suppression of spermatogenesis by bisdichloroacetyldiamines is mediated by inhibition of testicular retinoic acid biosynthesis.双二氯乙酰二胺对精子发生的抑制作用是通过抑制睾丸视黄酸生物合成介导的。
J Androl. 2011 Jan-Feb;32(1):111-9. doi: 10.2164/jandrol.110.010751. Epub 2010 Aug 12.
3
Inhibition of retinoic acid biosynthesis by the bisdichloroacetyldiamine WIN 18,446 markedly suppresses spermatogenesis and alters retinoid metabolism in mice.双二氯乙酰二胺WIN 18,446对维甲酸生物合成的抑制作用显著抑制了小鼠的精子发生并改变了类视黄醇代谢。
J Biol Chem. 2014 May 23;289(21):15104-17. doi: 10.1074/jbc.M113.540211. Epub 2014 Apr 7.
4
Return to fertility, toxicology, and transgenerational impact of treatment with WIN 18,446, a potential male contraceptive, in mice.恢复生育能力、毒理学以及 WIN 18,446（一种潜在的男性避孕药）治疗对小鼠的跨代影响。
Contraception. 2024 Jan;129:110306. doi: 10.1016/j.contraception.2023.110306. Epub 2023 Oct 7.
5
New approaches to male non-hormonal contraception.男性非激素避孕的新方法。
Contraception. 2013 Mar;87(3):296-9. doi: 10.1016/j.contraception.2012.08.016. Epub 2012 Sep 17.
6
Inhibition of retinoic acid synthesis disrupts spermatogenesis and fecundity in zebrafish.维甲酸合成的抑制会破坏斑马鱼的精子发生和繁殖力。
Gen Comp Endocrinol. 2015 Jun-Jul;217-218:81-91. doi: 10.1016/j.ygcen.2015.02.002. Epub 2015 Feb 14.
7
Down-regulation of the liver-derived plasma protein fetuin-B mediates reversible female infertility.肝脏来源的血浆蛋白胎球蛋白-B的下调介导可逆性女性不孕。
Mol Hum Reprod. 2017 Jan;23(1):34-44. doi: 10.1093/molehr/gaw068. Epub 2016 Oct 12.
8
Hyperglycaemia potentiates the teratogenicity of retinoic acid in diabetic pregnancy in mice.高血糖会增强糖尿病小鼠孕期视黄酸的致畸性。
Diabetologia. 2004 Mar;47(3):515-522. doi: 10.1007/s00125-004-1350-6. Epub 2004 Feb 14.
9
Suppression of Stra8 expression in the mouse gonad by WIN 18,446.WIN 18,446 抑制小鼠性腺中 Stra8 的表达。
Biol Reprod. 2011 May;84(5):957-65. doi: 10.1095/biolreprod.110.088575. Epub 2011 Jan 5.
10
Short- and long-term effect of contraceptive methods on fecundity.避孕方法对生育力的短期和长期影响。
Eur J Contracept Reprod Health Care. 2019 Aug;24(4):260-265. doi: 10.1080/13625187.2019.1621999. Epub 2019 Jun 21.
引用本文的文献
1
Determination of pharmacological inhibition of ALDH2 by ethanol clearance in mice.通过小鼠体内乙醇清除率测定乙醛脱氢酶2（ALDH2）的药理学抑制作用。
Toxicol Appl Pharmacol. 2024 Feb;483:116801. doi: 10.1016/j.taap.2023.116801. Epub 2024 Jan 4.
2
Return to fertility, toxicology, and transgenerational impact of treatment with WIN 18,446, a potential male contraceptive, in mice.恢复生育能力、毒理学以及 WIN 18,446（一种潜在的男性避孕药）治疗对小鼠的跨代影响。
Contraception. 2024 Jan;129:110306. doi: 10.1016/j.contraception.2023.110306. Epub 2023 Oct 7.
本文引用的文献
1
Retinoic Acid Regulates Calcium Signaling to Promote Mouse Ovarian Granulosa Cell Proliferation.视黄酸调节钙信号传导以促进小鼠卵巢颗粒细胞增殖。
Biol Reprod. 2016 Sep;95(3):70. doi: 10.1095/biolreprod.115.136986. Epub 2016 Aug 3.
2
De Novo-Synthesized Retinoic Acid in Ovarian Antral Follicles Enhances FSH-Mediated Ovarian Follicular Cell Differentiation and Female Fertility.卵巢窦卵泡中从头合成的视黄酸增强促卵泡激素介导的卵巢卵泡细胞分化和雌性生育力。
Endocrinology. 2016 May;157(5):2160-72. doi: 10.1210/en.2015-2064. Epub 2016 Mar 29.
3
Inhibition of retinoic acid biosynthesis by the bisdichloroacetyldiamine WIN 18,446 markedly suppresses spermatogenesis and alters retinoid metabolism in mice.双二氯乙酰二胺WIN 18,446对维甲酸生物合成的抑制作用显著抑制了小鼠的精子发生并改变了类视黄醇代谢。
J Biol Chem. 2014 May 23;289(21):15104-17. doi: 10.1074/jbc.M113.540211. Epub 2014 Apr 7.
4
Suppression of spermatogenesis by bisdichloroacetyldiamines is mediated by inhibition of testicular retinoic acid biosynthesis.双二氯乙酰二胺对精子发生的抑制作用是通过抑制睾丸视黄酸生物合成介导的。
J Androl. 2011 Jan-Feb;32(1):111-9. doi: 10.2164/jandrol.110.010751. Epub 2010 Aug 12.
5
Meiosis initiation in the human ovary requires intrinsic retinoic acid synthesis.人类卵巢中的减数分裂起始需要内在的视黄酸合成。
Hum Reprod. 2010 Oct;25(10):2579-90. doi: 10.1093/humrep/deq195. Epub 2010 Jul 29.
6
The role of vitamin A in mammalian reproduction and embryonic development.维生素A在哺乳动物生殖和胚胎发育中的作用。
Annu Rev Nutr. 2002;22:347-81. doi: 10.1146/annurev.nutr.22.010402.102745E.
7
Nonsteroid nuclear receptors: what are genetic studies telling us about their role in real life?非甾体类核受体：遗传学研究如何向我们揭示它们在实际中的作用？
Cell. 1995 Dec 15;83(6):859-69. doi: 10.1016/0092-8674(95)90202-3.
8
Embryocidal action of a bis(dichloroacetyl)-diamine: an oral abortifacient for rats.双（二氯乙酰）-二胺的杀胚胎作用：一种大鼠口服堕胎药。
Am J Obstet Gynecol. 1974 Jul 1;119(5):583-8. doi: 10.1016/0002-9378(74)90117-3.
9
Teratogenic action of bis(dichloroacetyl)diamine on rats: patterns of malformations produced in high incidence at time-limited periods of development.
Teratology. 1978 Aug;18(1):5-15. doi: 10.1002/tera.1420180104.
Zotero 插件