Functional in vitro model to examine cancer therapy cytotoxicity in maturing rat testis.
Childhood cancer treatment can lead to infertility. Organ culture of early postnatal testicular tissue might provide a valuable approach to the study of acute testicular toxicity. The aim of the present study was to develop a functional in vitro organ culture method, in order to identify sensitive target cells to doxorubicin-induced cytotoxicity in immature rat testis during germ cell migration prior initiation of the first wave of spermatogenesis. Testicular tissue fragments from 5-day-old Sprague-Dawley rats were cultured in the absence or presence of doxorubicin (40 and 100ng/ml) and morphology, apoptosis, proliferation and testosterone secretion was analyzed. Postnatal testicular development proceeded normally in control samples for 48h in vitro. In these untreated culture conditions germ and Sertoli cell numbers and germ cell migration were comparable to in vivo. Germ cells were the primary, most sensitive targets for in vitro-induced doxorubicin (100ng/ml) toxicity and their death was not associated with any morphological defects in the Sertoli cells. Organ culture which reduces the need of animal experimentation can be used to study the cytotoxic effects of doxorubicin on the immature testis.
Nurmio
Mirja
M
Department of Physiology, University of Turku, FIN-20520 Turku, Finland. mirja.nurmio@utu.fi
Toppari
Jorma
J
Kallio
Jenny
J
Hou
Mi
M
Söder
Olle
O
Jahnukainen
Kirsi
K
D023401:Animal Use Alternatives; D000818:Animals; D000831:Animals, Newborn; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D005854:Germ Cells / Q000187:drug effects; D008297:Male; D009924:Organ Culture Techniques / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D013739:Testosterone; D004317:Doxorubicin; D004247:DNA; D013936:Thymidine