Fang V S, Anderson W A
Endocrinology. 1976 Aug;99(2):358-70. doi: 10.1210/endo-99-2-358.
Both prepubertal and adult rats were treated with a single oral dose of either 60 mg or 120 mg of dl-6-(N-pipecolinomethyl)-5-hydroxy indane maleate (PMHI) per kg of body weight. Their testicular weights were drastically reduced compared with those of the controls. A follow-up, beginning on the third day post-treatment and continuing for a period of 50 days, showed that the body weight growth of PMHI-treated rats was not retarded. The hormonal profile indicated that, except for FSH which showed a transitory elevation in PMHI-treated immature rats, the serum levels of LH, estrogen, and testosterone were indistinguishable from those of the controls. Testicular histology revealed that the spermatogenic process in PMHI-treated rats recovered at a dose-related rate. EM sections of testes of adult rats indicated that cytoplasmic vacuolation appeared in the Sertoli cells 5 h post-treatment. The consequent cascade of arrested spermiogenesis included abnormal acrosomal condensation of spermatids and sloughing of polynucleated spermatids. Some spermatocytes also seemed to be affected, but spermatogonia and Leydig cells remained intact. These results indicate the PMHI acts primarily on Sertoli cells and causes arrest in the spermiogenetic stage of the spermatids. At a higher and toxic dose of PMHI, however, the earlier germinal elements might also be affected, due to the extensive damage to the supporting Sertoli cells.
对青春期前和成年大鼠均给予单次口服剂量为每千克体重60毫克或120毫克的dl-6-(N-哌啶甲基)-5-羟基茚满马来酸盐（PMHI）。与对照组相比，它们的睾丸重量显著降低。从治疗后第三天开始并持续50天的随访表明，接受PMHI治疗的大鼠体重增长并未受到抑制。激素水平表明，除了在接受PMHI治疗的未成熟大鼠中促卵泡激素（FSH）出现短暂升高外，促黄体生成素（LH）、雌激素和睾酮的血清水平与对照组并无差异。睾丸组织学检查显示，接受PMHI治疗的大鼠生精过程以剂量相关的速率恢复。成年大鼠睾丸的电镜切片表明，治疗后5小时支持细胞出现胞质空泡化。随后精子发生停滞的一系列变化包括精子细胞顶体异常浓缩和多核精子细胞脱落。一些精母细胞似乎也受到影响，但精原细胞和间质细胞保持完整。这些结果表明，PMHI主要作用于支持细胞，并导致精子细胞的精子形成阶段停滞。然而，在较高的毒性剂量下，由于支持性的支持细胞受到广泛损伤，早期的生殖细胞成分也可能受到影响。
