Neonatal phytoestrogen exposure causes hypospadias in female mice.
Neonatal phytoestrogen exposure causes hypospadias in female mice.
复制标题
新生期植物雌激素暴露会导致雌性小鼠出现尿道下裂。
DOI：
10.1002/mrd.21395
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发表时间：
2012
影响因子：
2.5
通讯作者：
Williams,CarmenJ
中科院分区：
文献类型：
--
作者：
Padilla-Banks,Elizabeth;Jefferson,WendyN;Myers,PageH;Goulding,DavidR;Williams,CarmenJ
We use a mouse model of neonatal exposure to the phytoestrogen genistein as a model of human infant exposure to soy formula (Jefferson and Williams 2011). Female CD-1 mice given 50 mg/kg/day genistein subcutaneously on postnatal days 1–5 have serum genistein levels of 1–5 µM, which closely approximates serum genistein levels measured in human infants fed soy formula. The genistein-treated mice are completely infertile due to functional abnormalities of the female reproductive tract. While performing these studies, we noted that the mice formed vaginal plugs that were softer and more yellow in appearance than in controls, and their external genitalia appeared abnormal. At 3 weeks of age, the clitoris was abnormally widened and erythematous, and the urethral opening was located at varying positions on the ventral aspect rather than at the distal tip of the clitoris as observed in controls (Fig. 1A, B). At 6 weeks of age, the clitoris was less erythematous, but the urethral opening remained abnormally positioned (Fig 1C, D). We confirmed that the observed opening was the urethra by euthanizing the mice and passing a suture from the bladder through the urethra to its exit point on the clitoris (Fig. 1E, F). This female hypospadias phenotype was completely penetrant as 10/10 Gen-treated females had hypospadias compared to 0/10 controls.The mammalian urethra forms from medial fusion of the urethral folds that arise from urogenital sinus mesenchyme. In humans of both sexes and in male mice, urethral development is completed prenatally. In males, this is an androgen-dependent process and can be disrupted by prenatal exposure to steroid hormones. In female mice, development of the distal vagina and urethra is incomplete until after birth. Neonatal exposure of female mice to diethylstilbestrol (DES) causes hypospadias as a result of dorsal urethral and sinus cord apoptosis, combined with failure of both urethral-fold fusion and distal urethral migration (Miyagawa et al. 2002). Excretion of urine through this abnormal location likely explains the accumulation of vaginal crystals observed in female mice exposed to DES (Takasugi and Bern 1962).
