Robertson K M, Simpson E R, Lacham-Kaplan O, Jones M E
Prince Henry's Institute of Medical Research, Monash Medical Centre, Clayton, Victoria, Australia.
J Androl. 2001 Sep-Oct;22(5):825-30.
Previous studies employing the male aromatase knockout (ArKO) mouse have indicated that local expression of estrogens appears to be important for the progression of spermatogenesis. In the absence of estrogen biosynthesis round spermatids are observed to undergo apoptosis and thus fail to differentiate into mature, elongated spermatids. This lesion appears to arise between the ages of 18 weeks and 1 year. To ultimately determine if the disruption to spermatogenesis arises earlier than 18 weeks, we performed an intensive study to examine the fertility of younger male ArKO mice. This involved an analysis of their mating capacity together with an extensive stereological analysis, determination of the in vitro potential of mature sperm, and sexual behavior. ArKO and wild-type (w/t) males at 7 weeks of age were placed with w/t females for 7 weeks. At age 14 weeks, the males were killed and the testes removed. ArKO mice were observed to sire significantly fewer litters than the w/t mice; 5 out of the 10 sired no litters at all. Stereological analysis performed on the removed testes found a significant decrease in round spermatid numbers between w/t and ArKO mice at this age; however, there were no differences in all other germ cells and Sertoli cell numbers. When mature spermatozoa were analyzed, sperm from 15-week-old ArKO mice had a significant reduction in motility. This was further reduced by 1 year of age with a decrease in concentration. A preliminary examination of sexual behavior found that ArKO mice did not attempt to mount the females, in contrast to the w/t mice, which mounted consistently during the time period. In conclusion, we observed that ArKO mice have reduced fertility at age 14 weeks. This may be due in part to a disruption in spermatogenesis because the phenotype does appear to arise earlier than 18 weeks, possibly leading to abnormalities in the mature spermatozoa. Or, in part, this may be attributable to an impairment in the development of copulatory behavior, which is consistent with the available evidence that points to a crucial role for estrogens in the neural development and initiation of male sexual behavior.
以往利用雄性芳香化酶基因敲除（ArKO）小鼠开展的研究表明，雌激素的局部表达似乎对精子发生的进程至关重要。在缺乏雌激素生物合成的情况下，观察到圆形精子细胞会发生凋亡，因而无法分化为成熟的、伸长的精子细胞。这种损害似乎出现在18周龄至1岁之间。为了最终确定精子发生的破坏是否早于18周出现，我们进行了一项深入研究，以检查较年轻雄性ArKO小鼠的生育能力。这包括对它们的交配能力进行分析，同时进行广泛的体视学分析、测定成熟精子的体外潜能以及性行为分析。将7周龄的ArKO雄性小鼠和野生型（w/t）雄性小鼠与w/t雌性小鼠放在一起7周。在14周龄时，处死雄性小鼠并摘除睾丸。观察到ArKO小鼠产仔的窝数明显少于w/t小鼠；10只ArKO小鼠中有5只根本没有产仔。对摘除的睾丸进行体视学分析发现，在这个年龄，w/t小鼠和ArKO小鼠之间圆形精子细胞数量显著减少；然而，所有其他生殖细胞和支持细胞的数量没有差异。当对成熟精子进行分析时，15周龄ArKO小鼠的精子活力显著降低。到1岁时，活力进一步降低，精子浓度也下降。对性行为的初步检查发现，与w/t小鼠不同，ArKO小鼠没有试图骑跨雌性小鼠，而w/t小鼠在这段时间内持续有骑跨行为。总之，我们观察到ArKO小鼠在14周龄时生育能力下降。这可能部分归因于精子发生的破坏，因为这种表型似乎确实早于18周出现，可能导致成熟精子异常。或者，部分原因可能是交配行为发育受损，这与现有证据一致，即雌激素在雄性性行为的神经发育和启动中起关键作用。
