Protection from procarbazine-induced testicular damage by hormonal pretreatment does not involve arrest of spermatogonial proliferation

• Published in: Cancer research (Chicago, Ill.) Vol. 57; no. 6; pp. 1091 - 1097
• Main Authors: MEISTRICH, M. L, WILSON, G, ZHANG, Y, KURDOGLU, B, TERRY, N. H. A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.03.1997
• Subjects: Animals; Biological and medical sciences; Cell Division - drug effects; DNA Replication - drug effects; Drug Administration Schedule; Drug Implants; Drug toxicity and drugs side effects treatment; Estradiol - administration & dosage; Estradiol - therapeutic use; Growth Inhibitors - toxicity; Infertility, Male - chemically induced; Infertility, Male - prevention & control; Male; Medical sciences; Pharmacology. Drug treatments; Procarbazine - toxicity; Rats; Spermatogenesis - drug effects; Spermatogonia - drug effects; Spermatogonia - pathology; Testosterone - administration & dosage; Testosterone - therapeutic use; Toxicity: urogenital system; Antineoplastic agent; Procarbazine; Drug combination; Androgen; Rat; Spermatogenesis; Toxicity; Estrogen; Rodentia; Testicle; Male genital system; Estradiol; Prevention; Testosterone; Vertebrata; Mammalia; Cytoprotector; Animal; Sex steroid hormone; Mechanism of action
• ISSN: 0008-5472; 1538-7445

Hormone treatments that suppress sperm production enhance the recovery of spermatogenesis after gonadal exposure to various cytotoxic agents. It has generally been assumed that the mechanism of protection involved an arrest of spermatogonial kinetics. To test this hypothesis critically, we examined spermatogonial kinetics and numbers in rats in which the completion of spermatogenesis was suppressed with a 6-week testosterone plus 17beta-estradiol treatment that protected the testis from procarbazine-induced damage. Histological examination showed that the numbers of A-aligned, intermediate, and B spermatogonia and preleptotene spermatocytes and their mitoses were unaffected by testosterone plus 17beta-estradiol treatment. Flow cytometric analysis of bromodeoxyuridine-labeled cells showed that the percentage of diploid cells undergoing DNA synthesis, the progression of B spermatogonia and preleptotene spermatocytes through S-phase, the division of intermediate and B spermatogonia, the entry of intermediate spermatogonia into their next S-phase as type B cells, and the progression of cells through meiotic prophase were either unchanged or very slightly increased. Thus, changes in spermatogonial numbers or suppression of their proliferation cannot account for protection of spermatogenesis from exposure to cytotoxic agents.