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Persistent Impairment of Testicular Histology and Sperm Motility in Adult Rats Treated with Cisplatin at Peri-puberty

Grant number: 11/17128-4
Support type:Regular Research Grants - Publications - Scientific article
Duration: September 01, 2011 - February 29, 2012
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Ana Paula Alves Favareto
Grantee:Ana Paula Alves Favareto
Home Institution: Faculdade de Ciências, Letras e Educação. Universidade do Oeste Paulista (UNOESTE). Campus de Presidente Prudente. Presidente Prudente , SP, Brazil

Abstract

Cisplatin is one of the most widely used and effective chemotherapeutic agents for the treatment of several humanmalignancies. This study evaluated the effects of peri-pubertal cisplatin administration on several reproductive end-points andthe reversibility of these effects in adulthood. Peri-pubertal Wistar male rats (45 days old) were divided into two groups: control(saline 0.9%) and cisplatin (1 mgD kg D day, 5 days Dweek, for 3 weeks, i.p.). The study was conducted in two steps and evaluationswere performed at ages of 66 (post-pubertal age) and 140 (adult age) days on: (i) organ weights, serum gonadotropinsand testosterone levels, sperm counts, motility and morphology, testicular histomorphometry, spermatogenesis kinetics, Sertolicell number and in situ detection of apoptotic germ cells and (ii) sexual behaviour, fertility and intratesticular testosterone. Atthe end of cisplatin therapy, rats showed reductions in sperm production and reserves, sperm with progressive movement,tubular diameter, intratesticular testosterone and fertility potential, but increased numbers of TUNEL-positive seminiferoustubules, immotile sperm and pre-implantation losses compared with control. Moreover, cisplatin-treated post-pubertal rats displayedimpaired testicular histopathology and sexual behaviour. Serum gonadotropins and testosterone levels, sperm morphology,spermatogenesis kinetics and Sertoli cell number were comparable between experimental groups at both ages. Alterationsfound in post-puberty were recovered at adulthood, except for sperm motility and damage to testicular histology. The persistenceof these cisplatin effects, despite the unaltered fertility after natural mating in rats, may have implications for reproductivefunction of young boys undergoing cancer therapy, given the lower reproductive efficiency in human beings comparedwith rats. (AU)