Effects of AF 1312 TS and Lonidamine on Mammalian Testis. A Morphological Study

Effects of Lonidamine on Pituitary-Gonadal Axis in Man

“…It has been shown that this drug affects both Sertoli and germ cells. In the rat, Lonidamine induces vacuolization and retraction of the apical cytoplasm of Sertoli cells within 24 h, with consequent exfoliation of the immature germ cells into the tubular lumen; later on spermatids and spermatocytes show altered mitochondria, vacuolized nuclei, pyknosis, and karyolysis and appearance of many multinucleated germ cells [4], Similar morphological changes have been described in other mammalian species, including rabbit, beagle dog, and monkey. Spermatogonia do not show any ultrastructural al terations [4], It has been reported that Lonidamine affects the "condensed" [17] mitochondria [8,18,19], reducing cell respiration and consequently increasing glycolysis.…”

“…2). Lonidamine is the most active com pound of this class, and its effects on spermatogenesis are now well documented in several animal species [3][4][5][6][7]. Besides offering a promising tool to the nonhormonal approach to male contraception.…”

Anchoring Junctions As Drug Targets: Role in Contraceptive Development

“…Initial studies with lonidamine demonstrated that oral administration to adult rats (50 -200 mg/kg b.wt.) induced depletion of germ cells from the seminiferous epithelium, resulting in infertility (Lobl et al, 1979;De Martino et al, 1981;Lobl et al, 1981). At the ultrastructural level, lonidam-ANCHORING JUNCTIONS AND MALE CONTRACEPTION ine was shown to noticeably cause retraction of the apical cytoplasm in Sertoli cells (Lobl et al, 1979;De Martino et al, 1981;Marcante et al, 1981;Malorni et al, 1992).…”

“…induced depletion of germ cells from the seminiferous epithelium, resulting in infertility (Lobl et al, 1979;De Martino et al, 1981;Lobl et al, 1981). At the ultrastructural level, lonidam-ANCHORING JUNCTIONS AND MALE CONTRACEPTION ine was shown to noticeably cause retraction of the apical cytoplasm in Sertoli cells (Lobl et al, 1979;De Martino et al, 1981;Marcante et al, 1981;Malorni et al, 1992). Shortly thereafter, it became clear that this drug targets Sertoli cell stress fibers by disrupting actin dynamics (Malorni et al, 1992), thereby resulting in changes in Sertoli cell morphology, such as vacuolization and germ cell loss from the seminiferous epithelium, instead of targeting dividing germ cells.…”

Lonidamine, a New Approach to Cancer Therapy

“…It is known that during spermatogenesis the mito chondria of rat germ cells undergo morphological changes [22][23][24][25][26][27], gradually passing from the orthodox to the condensed form [25,27]; the condensed mito chondrion is the morphologic expression of a func tional state, characterized by a high oxidative capacity associated with a pronounced phosphorylation effi cacy [24], Germ cells with condensed mitochondrion are those susceptible to Lonidamine. Moreover, the cytotoxic activity of this drug or its active analogs is preceded by specific changes of germ cell mitochon dria [14,15,20]. Hence, the indication that the con densed mitochondrion is the target for Lonidamine.…”