Effects of cis-platinum and luteinizing hormone releasing hormone analogues on rat spermatogenesis. A morphologic and flow cytometric study.
OBJECTIVE
To evaluate morphologically and flow cytometrically the effects of cis-platinum (cis-diaminedichloroplatinum [CDDP]) administered acutely and chronically with and without gonadotropin releasing hormone analogue (LRA) pretreatment on adult rats to verify the feasibility of protecting the spermatic epithelium before chemotherapy.


METHODS
Six groups of adult Wistar rats were studied: 2 were treated with an LD50 dose of CDDP in single and 2 in multiple administrations, 1 of each was pretreated with LRA and 1 LRA control and one untreated group were also evaluated. Relative frequency of spermatogenic phases, qualitative alterations, Johnsen's score and percentage of cells in each DNA region were determined.


RESULTS
Acute CDDP treatment reduced spermatids, spermatozoa and haploid cells. Chronic CDDP treatment induced in some rats a reduction in tetraploid cells and in others an increase associated with morphologically abnormal spermatids and cells showing aberrant hypodiploid content in analogy to all chronic CDDP LRA-pretreated animals.


CONCLUSIONS
Single-dose CDDP reduces spermatids by killing rapidly cycling spermatogonia and inducing alterations in maturation; in repeated doses, more marked reductions in spermatogonia are seen, followed by a compensatory proliferation of residual stem cells with generation of cells with an aberrant DNA content. These alterations are not prevented by LRA treatment sufficient to determine inhibition of serum testosterone levels.
Institute of Pathological Anatomy and Histopathology, School of Medicine, University of Udine, Italy.
C A
CA
Scott
L
L
Desinan
M
M
Maffezzini
A
A
Simonato
C
C
Avellini
S
S
De Stefani
V
V
Rizzi
G
G
Carmignani
C A
CA
Beltrami
D000818:Animals; D002945:Cisplatin / Q000494:pharmacology*; D004247:DNA / Q000032:analysis*; D005434:Flow Cytometry; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*; D008297:Male; D011003:Ploidies; D051381:Rats; D017208:Rats, Wistar; D013091:Spermatogenesis / Q000187:drug effects*; D013094:Spermatozoa / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D013737:Testis / Q000737:chemistry / Q000187:drug effects / Q000473:pathology
D007987:Gonadotropin-Releasing Hormone; D004247:DNA; D002945:Cisplatin