Miller T A, Scott W J
Children's Hospital Research Foundation, Cincinnati, Ohio.
Teratology. 1992 Dec;46(6):541-50. doi: 10.1002/tera.1420460603.
These experiments more accurately define the effects of the combination acetazolamide-amiloride or a single dose of dimethadione (DMO), the active metabolite of trimethadione, on the development of the ureter. When acetazolamide-amiloride was administered in C57BL/6NCrlBR mice on day 9, 9.5, or 10 of gestation (plug = day 0) a second ureter was formed, anterior to the original ureter, inducing a second kidney. The second ureter then fails to make a connection with the developing bladder and remains attached to the mesonephric duct. The mesonephric duct becomes the vas deferens in the male and deteriorates completely in the female leading to either a restricted ureter or a blocked ureter depending on the sex of the fetus. Administration of a single dose of DMO between gestational day 9 and 10.3 produced both renal agenesis and ureters of varying lengths. Some ureters were of normal length with a tuft of one or two nephrons at their tip, while others were one half or one quarter of their normal length. In some instances the ureter was completely absent. The reason for this strong effect on the ureter is unknown.
这些实验更准确地界定了乙酰唑胺 - 阿米洛利组合或三甲双酮的活性代谢物二甲双酮（DMO）的单剂量对输尿管发育的影响。当在妊娠第9天、9.5天或10天（交配日 = 第0天）给C57BL / 6NCrlBR小鼠施用乙酰唑胺 - 阿米洛利时，在原始输尿管前方会形成第二条输尿管，进而诱导出第二个肾脏。然后，第二条输尿管未能与发育中的膀胱建立连接，并仍附着于中肾管。中肾管在雄性中成为输精管，而在雌性中则完全退化，这取决于胎儿的性别，从而导致输尿管受限或堵塞。在妊娠第9天至10.3天之间给予单剂量的DMO会导致肾发育不全和不同长度的输尿管。一些输尿管长度正常，其顶端有一丛一两个肾单位，而其他输尿管则为正常长度的一半或四分之一。在某些情况下，输尿管完全缺失。这种对输尿管产生强烈影响的原因尚不清楚。
