title: Lonidamine transiently affects spermatogenesis in pubertal CD1 mice.
abstract: Lonidamine (LND) [1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid], a well-known antispermatogenic drug, was studied for the first time in pubertal mice to assess its possible effects on spermatogenesis. Male CD1 mice were orally treated on Postnatal Day (PND) 28 with a single dose of LND (100 mg/kg body weight) and sacrificed on PND30, PND42, PND74 and PND123. On PND30 (48 h after dosing), severe testicular effects were evidenced in the treated animals: (a) reduction of the testicular sperm head concentration (approximately 50% of the control value); (b) changes in the spermatogenic cell type distribution (mild decrease of the elongated spermatids and S-phase cells fractions); and (c) morphological alterations of the Sertoli cell cytoplasm and germ cell exfoliation. These changes were recovered in adulthood, on PND74 and PND123. However, no effect on sperm chromatin structure was detected on the epididymal sperm of mature mice by sperm chromatin structure assay, suggesting that LND did not interfere with the process of chromatin reorganization and DNA packaging.
authors.affiliation: Department of Drug Research and Evaluation, Istituto Superiore di Sanità, 00161 Rome, Italy. traina@iss.it
authors.forename: Maria Elsa
authors.initials: ME
authors.lastname: Traina
authors.forename: Maria
authors.initials: M
authors.lastname: Guarino
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Urbani
authors.forename: Luciano
authors.initials: L
authors.lastname: Saso
authors.forename: Patrizia
authors.initials: P
authors.lastname: Eleuteri
authors.forename: Eugenia
authors.initials: E
authors.lastname: Cordelli
authors.forename: Michele
authors.initials: M
authors.lastname: Rescia
authors.forename: Giorgio
authors.initials: G
authors.lastname: Leter
authors.forename: Marcello
authors.initials: M
authors.lastname: Spanò
mesh_terms: D000818:Animals; D000988:Antispermatogenic Agents / Q000494:pharmacology*; D002843:Chromatin / Q000648:ultrastructure; D004247:DNA / Q000032:analysis; D005434:Flow Cytometry; D007191:Indazoles / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D012741:Sexual Maturation; D013076:Sperm Count; D013077:Sperm Head; D013091:Spermatogenesis / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D013737:Testis / Q000648:ultrastructure
chemical_list: D000988:Antispermatogenic Agents; D002843:Chromatin; D007191:Indazoles; D004247:DNA; C016371:lonidamine