The antiestrogen ICI 182,780 induces early effects on the adult male mouse reproductive tract and long-term decreased fertility without testicular atrophy.
The antiestrogen ICI 182,780 induces early effects on the adult male mouse reproductive tract and long-term decreased fertility without testicular atrophy.
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DOI：
10.1186/1477-7827-1-57
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发表时间：
2003-08-18
期刊：
影响因子：
--
通讯作者：
Hess RA
中科院分区：
文献类型：
--
作者：
Cho HW;Nie R;Carnes K;Zhou Q;Sharief NA;Hess RA
雌激素受体（ER）在女性和男性生殖系统中具有重要的生理作用。先前使用雌激素受体-α敲除小鼠（αERKO）或抗雌激素治疗成年啮齿动物的研究表明，ERα对雄性生殖道的正常功能至关重要。在本研究中，测定了抗雌激素ICI 182，780的时间效应，以更好地了解成年男性的ERα功能。将30日龄的成年雄性小鼠皮下注射ICI 182，780（5 mg），每周一次，持续17周。通过血管灌注固定组织以研究处理后第2天至第125天的时间响应。未观察到给药导致的体重差异。睾丸重量在第59天降低18%，在第125天降低21.4%。其他显著的给药相关效应包括：1）睾丸网和输出小管管腔扩张; 2）睾丸网和输出小管上皮高度降低; 3）输出小管核上上皮细胞质高度降低; 4）输出小管上皮微绒毛高度降低，尤其是近端小管; 5）附睾输出小管无纤毛上皮细胞内PAS阳性颗粒和内吞小泡减少，6）附睾起始段狭窄细胞形成帽状和囊泡，7）附睾头顶端细胞内PAS阳性颗粒增多，8）附睾上皮细胞内PAS阳性颗粒增多，10）附睾上皮细胞内PAS阳性颗粒增多，10）附睾上皮细胞内PAS阳性颗粒增多，10）附睾上皮细胞内PAS阳性颗粒增多。8）附睾体和尾部透明细胞中溶酶体颗粒增加; 9）萎缩的生精小管和异常精子发生的有限诱导;和10）尾部精子浓度降低、精子运动性和生育力降低。对青春期雄性小鼠进行抗雌激素治疗导致的生殖效应与早在第4天在αERKO小鼠中观察到的生殖效应相似;然而，睾丸重量并未显著增加，并且在延长治疗期间未观察到总萎缩。
Estrogen receptors (ER) have important physiological roles in both the female and male reproductive systems. Previous studies using the estrogen receptor-α knockout mouse (αERKO) or antiestrogen treatment in adult rodents have shown that ERα is essential for normal function of the male reproductive tract. In the present study, time-response effects of the antiestrogen ICI 182,780 were determined to better understand ERα function in the adult male. Adult male mice, 30 days old, were injected subcutaneously with ICI 182,780 (5 mg) once per week for 17 weeks. Tissues were fixed by vascular perfusion to study the time responses from day 2 to 125 post treatment. No difference was seen in body weight due to treatment. Testis weight was decreased 18% on day 59 and 21.4% on day 125. Other significant treatment-related effects included the following: 1) dilation of rete testis and efferent ductule lumen; 2) decreased height of the rete testis and efferent ductule epithelium; 3) decreased height of the supranuclear epithelial cytoplasm in efferent ductules; 4) decreased height of the efferent ductule epithelial microvilli, particularly in the proximal ductules; 5) decrease in the PAS-positive granules and endocytotic vesicles in nonciliated epithelial cells of efferent ductules; 6) capping and vesiculation of narrow cells in the initial segment of the epididymis; 7) accumulation of PAS-positive granules in apical cells of the caput epididymis; 8) increase in lysosomal granules in clear cells of the corpus and cauda epididymis; 9) limited induction of atrophic seminiferous tubules and abnormal spermatogenesis; and 10) decreases in the concentration of cauda sperm, progressive sperm motility and decreased fertility. Antiestrogen treatment of the pubertal male mouse resulted in reproductive effects similar to those observed in the αERKO mouse as early as day 4; however, testis weight did not increase substantially and total atrophy was not observed with extended treatment.