Rout Ujjwal Kumar, Armant D Randall
Department of Obstetrics & Gynecology, C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, 275 East Hancock, Detroit, MI 48201, USA.
Reprod Toxicol. 2002 May-Jun;16(3):253-8. doi: 10.1016/s0890-6238(02)00022-9.
Alcohols and aldehydes are metabolized primarily by alcohol (ADH) and aldehyde (ALDH) dehydrogenase isozymes. Although significant progress has been made towards understanding the involvement of these isozymes in the oxidation of alcohol and aldehydes in the body, it is not known how these compounds are handled during fertilization and preimplantation embryogenesis. In this study, reverse transcription and the polymerase chain reaction (RT-PCR) was used to determine which ADH and ALDH isozymes are expressed at the oocyte, zygote, morula, and blastocyst stages of preimplantation development in the mouse. Transcripts of beta-actin and vimentin, assayed as controls, were detected at all stages, as well as Class III ADH (Adh-2) and Class 3 ALDH (Ahd-4), involved in the detoxification of formaldehyde and aromatic aldehydes, respectively. In contrast, transcripts for the major ethanol oxidizing isozyme, Class I ADH (Adh-1) was not detected during preimplantation development. Cytosolic retinol dehydrogenase (Adh-3) transcripts were marginally detected in oocytes and zygotes. The mRNA for cytosolic retinal dehydrogenase (Ahd-2), microsomal short-chain retinol dehydrogenases (RoDH Type I), and the mitochondrial low-Km acetaldehyde dehydrogenase (Ahd-5) only appeared as maternal transcripts. Microsomal ALDH (Ahd-3), which is induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), was not expressed until the blastocyst stage. ADH and ALDH enzyme systems may guard mouse preimplantation embryos against the toxic effects of industrial pollutants, such as formaldehyde and TCDD, as well as peroxidatic aldehydes generated during lipid peroxidation. The absence of enzymes to convert ethanol to acetaldehyde, coupled with oocyte expression of the acetaldehyde-degrading enzyme, Ahd-5, may be protective for the early embryo.
醇类和醛类主要通过醇脱氢酶(ADH)和醛脱氢酶(ALDH)同工酶进行代谢。尽管在了解这些同工酶参与体内醇类和醛类氧化方面已经取得了重大进展,但尚不清楚这些化合物在受精和植入前胚胎发育过程中是如何被处理的。在本研究中,采用逆转录聚合酶链反应(RT-PCR)来确定在小鼠植入前发育的卵母细胞、受精卵、桑椹胚和囊胚阶段表达哪些ADH和ALDH同工酶。作为对照检测的β-肌动蛋白和波形蛋白的转录本在所有阶段均有检测到,同时还检测到分别参与甲醛和芳香醛解毒的Ⅲ类ADH(Adh-2)和3类ALDH(Ahd-4)。相比之下,在植入前发育过程中未检测到主要的乙醇氧化同工酶Ⅰ类ADH(Adh-1)的转录本。在卵母细胞和受精卵中仅微量检测到胞质视黄醇脱氢酶(Adh-3)的转录本。胞质视网膜脱氢酶(Ahd-2)、微粒体短链视黄醇脱氢酶(RoDHⅠ型)和线粒体低Km乙醛脱氢酶(Ahd-5)的mRNA仅作为母体转录本出现。由2,3,7,8-四氯二苯并对二恶英(TCDD)诱导的微粒体ALDH(Ahd-3)直到囊胚阶段才表达。ADH和ALDH酶系统可能保护小鼠植入前胚胎免受工业污染物如甲醛和TCDD以及脂质过氧化过程中产生的过氧化物醛的毒性影响。缺乏将乙醇转化为乙醛的酶,再加上卵母细胞中乙醛降解酶Ahd-5的表达,可能对早期胚胎具有保护作用。