ESTROGEN RECEPTORS IN MALE REPRODUCTION

最初的研究表明，男性生殖系统 在ER基因靶向破坏的小鼠中解剖学正常 （Lubahn等人，1993年）。尽管这些研究表明男性 突变ER基因纯合子（ERKO）的生育力再分析减少 的基因型确定，可育小鼠是杂合子的 突变我们随后证实雄性ERKO小鼠是不育的。 虽然生殖器官重量和血清LH和FSH水平 在4-6个月大的ERKO和野生型小鼠之间显著不同， 睾丸激素水平略有升高，精子数量和百分比 活动力降低，睾丸重量减少，交配减少 在ERKO中比在野生型雄性中更常见。无明显 ERKO和野生型雄性睾丸之间的组织学差异 出生后10天，但在20天及以后， ERKO小鼠的生精小管扩张。随后， ERKO小鼠中的小管变性，从尾极开始 生后70-90天睾丸的退化，最后发生 在6-8个月大时在颅极的小管中。我们的工作 一种假说认为，曲细精管的扩张是由 减少连接睾丸的5-8个输出管的重吸收 到附睾这是因为大约90%的液体离开 睾丸在传出小管中被钠泵重吸收 机制，他们含有较高水平的ER比其他男性 生殖道组织

Initial studies indicated that the male reproductive system is anatomically normal in mice with a targeted disruption in the ER gene (Lubahn et al., 1993). Although these studies indicated that male homozygous for the mutant ER gene (ERKO) had reduced fertility reanalysis of genotypes determined that the fertile mice were heterozygous for the mutation. We subsequently verified that male ERKO mice are sterile. Although reproductive organ weights and serum LH and FSH levels did not differ significantly between 4-6 month old ERKO and wild-type mice, testosterone levels were slightly elevated, sperm numbers and percent motility were reduced, testis weights were reduced, and mating was less frequent in ERKO than in wild-type males. There were no obvious histological differences between testes of ERKO and wild-type males at 10 days after birth, but at 20 days and thereafter thelumen of the seminiferous tubules were dilated in ERKO mice. There was subsequent degeneration of the tubules in ERKO mice, beginning at the caudal pole of the testis 70-90 days after birth, with degeneration occurring last in tubules at the cranial pole at 6-8 months of age. Our working hypothesis is that the dilation of the seminiferous tubules is caused by reduced reabsorption in the 5-8 efferent ducts that connect the testis to the epididymis. This is because approximately 90% of the fluid leaving the testis is reabsorbed in the efferent ductules by a sodium pump mechanism and they contain higher levels of ER than other male reproductive tract tissues.