EVIDENCE FROM SERTOLI CELL-DEPLETED RATS INDICATES THAT SPERMATID NUMBER IN ADULTS DEPENDS ON NUMBERS OF SERTOLI CELLS PRODUCED DURING PERINATAL-DEVELOPMENT
EVIDENCE FROM SERTOLI CELL-DEPLETED RATS INDICATES THAT SPERMATID NUMBER IN ADULTS DEPENDS ON NUMBERS OF SERTOLI CELLS PRODUCED DURING PERINATAL-DEVELOPMENT
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DOI：
10.1210/endo-122-3-787
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发表时间：
1988-03-01
期刊：
影响因子：
4.8
通讯作者：
LAMPERTI, AA
中科院分区：
文献类型：
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作者：
ORTH, JM;GUNSALUS, GL;LAMPERTI, AA
为了探讨围产期建立的支持细胞群大小与成年睾丸生殖细胞产生之间的关系，建立了支持细胞耗竭大鼠模型。这是通过将抗有丝分裂药物阿糖胞苷(Arac)直接输送到新生幼崽的睾丸来实现的。对这些接受Arac治疗的新生儿的初步研究表明，1)这种药物可以迅速从睾丸中清除；2)它大大降低了Sertoli细胞的增殖水平；3)尽管之前的药物治疗过，Sertoli细胞的分裂在正常情况下停止；以及4)Arac本身对生殖细胞的增殖没有残留的影响，这种作用在注射几天后就开始了。给予Arac的幼鼠被允许达到成熟，它们的睾丸被灌流固定进行光镜形态测量。当给予Arac AS的成年大鼠的支持细胞数量与正常胎鼠相比时，治疗组大鼠的支持细胞数量减少了54%，现在被称为支持细胞耗竭。此外，当对正常和支持细胞枯竭的成人的圆形精子细胞进行量化和比较时，后者的睾丸中圆形精子细胞的数量减少了55%。由于在Arac处理组中，支持细胞数量的减少与同等数量的精子细胞产量的减少相平行，因此在正常和支持细胞枯竭的动物中，每个支持细胞的圆形精子细胞的数量基本上是相同的。对两组大鼠血清雄激素结合蛋白(ABP)和卵泡刺激素(FSH)的测定表明，支持细胞耗竭大鼠的ABP循环水平约为正常大鼠的一半，FSH浓度约为正常动物的两倍。因此，即使在支持细胞耗竭的大鼠中FSH升高，每个支持细胞产生的ABP也没有变化。此外，支持细胞耗竭组大鼠间质细胞的总体积和腹侧前列腺重量均正常，提示这些大鼠的间质细胞功能正常。综上所述，在生殖细胞分裂开始之前，通过在出生后早期特异性地干扰支持细胞的增殖，已经产生了支持细胞耗竭的大鼠模型。此外，我们在这个模型中的发现表明，成人生殖细胞正常数量的产生至少部分取决于支持细胞群体的大小。因此，我们的观察确定了围产期，当支持细胞群建立时，对于成人数量上正常的精子发生的发展至关重要。
To probe the relationship between the size of the Sertoli cell population, established during perinatal development, and production of germ cells in the adult testis, a Sertoli cell-depleted rat model was developed. This was accomplished by delivering an antimitotic drug, cytosine arabinoside (araC), directly to the testis of newborn pups. Initial studies of these araC-treated neonates indicated that 1) the drug is cleared raidly from the testis; 2) its substantially reduces the level of Sertoli cell proliferation; 3) Sertoli cell division ceases at a normal time in spite of the previous drug treatment; and 4) araC itself has no residual effect on germ cell proliferation, which begins several days after the injection. Pups given araC were allowed to reach maturity, and their testes were perfuse-fixed for light microscopic morphometry. When the numbers of Sertoli cells in adult rats given araC as were compared with those in normal littermates, a 54% decrease in the size of the Sertoli cell population was detected in treated rats, now referred to as Sertoli cell-depleted. Moreover, when round spermatids were quantified and compared in normal and Sertoli cell-depleted adults, testes of the latter were found to contain 55% fewer round spermatids. Since, in the araC-treated group, the decrease in Sertoli cell population size was paralled by a reduction in spermatid production of equal magnitude, the number of round spermatids per Sertoli cell was essentially identical in normal and Sertoli cell-depleted animals. Measurements of serum androgen-binding protein (ABP) and FSH in both groups indicated that the circulating level of ABP in Sertoli cell-depleted rats was approximately half, and the concentration of FSH approximately twice, that in normal animals. Thus, even though FSH is elevated in Sertoli cell-depleted rats, the production of ABP per Sertoli cell is unchanged. In addition, collective volume of Leydig cells and ventral prostate weights were normal in the Sertoli cell-depleted group, suggesting that Leydig cell function in these rats is normal. In summary, a Sertoli cell-depleted rat model has been produced by interfering specifically with Sertoli cel proliferation early in postnatal life, before onset of germ cell division. Moreover, our findings with this model indicate htat production of normal numbers of germ cells in adults depends, at least in part, on the size of the Sertoli cell population. Thus, our observations identify the perinatal period, when the Sertoli cell population is established, as critical for development of quantitatively normal speratogenesis in the adult.