Sequential depletion of rat testicular lipids with long-chain and very long-chain polyenoic fatty acids after X-ray-induced interruption of spermatogenesis

Abstract

This article is available online at http://www.jlr.org motherapeutic drugs and X-ray irradiation. Precisely because of its effi cacy to kill rapidly dividing cells, exposure of the testis to these agents, whether incidental or therapeutic, selectively targets the population of spermatogenic cells and is a potential cause of male infertility. While somatic cells, including Sertoli cells, are apparently unaffected, spermatogonia that are mitotically dividing and spermatocytes during the early phases of meiosis are the testicular cells most vulnerable to X-rays ( 1 ). Relatively less susceptible are nondividing spermatogonial stem cells on the one hand and postmeiotic cells on the other. Spermatids and spermatozoa, with their much more compact nuclei, are notably resistant. Germ cell death induced by X-ray irradiation mostly occurs via apoptosis ( 2, 3 ), which results from radiation-induced free radical generation damaging DNA. The protein P53, the known intracellular sensor of DNA damage, is required for this response ( 1, 4 ). P53 upregulates in germ cells the production of Fas, the surface receptor that, on binding the Fas ligand produced by Sertoli cells, activates apoptosis via a caspase-mediated cascade ( 5, 6 ).A few weeks after having locally irradiated the testis with X-rays, spermatogenesis recommences from type A spermatogonial stem cells that had not been affected at irradiation time in some mammalian species like mice ( 1 ) but not in others like LBNF1 rats, which are in this regard a good model of the human testicular sensitivity to X-rays ( 7 ). In these rats, despite the presence and normal proliferation of apparently undamaged type A spermatogonia, it is their further differentiation that is after some time impeded, The mammalian testis is known to be highly susceptible to a variety of anticancer agents, including a number of che- This work was supported by funding from Consejo Nacional de Investigaciones Científi cas y Técnicas (CONICET), Agencia Nacional de Promoción de la Ciencia y la Tecnología (ANPCyT), and Universidad Nacional del Sur (UNS).

Differentiation-related changes in lipid classes with long-chain and very long-chain polyenoic fatty acids in rat spermatogenic cells

“…In vivo, after a single exposure to X rays, species of CE with 22:5n-6 steadily accumulate in the testis as it loses its germ cells, whereas 22:5n-6-rich TAG are virtually unchanged as long as spermatids continue to develop into spermatozoa ( 10 ). This observation suggested an association of CE with Sertoli cells and TAG with germ cells.…”

“…Those germ cells that survive irradiation are able to complete their differentiation and gradually leave the testis as spermatozoa, until only Sertoli cells remain in seminiferous tubules. This continuing germ cell depletion, taking a number of weeks, is concomitant to the exhaustion of SM and Cer species with both types of VLCPUFA ( 10 ). Species with n-VLCPUFA and with 2-OH VLCPUFA disappeared from the testis four and six weeks after irradiation, respectively, the former with the last spermatocytes, the latter with the last spermatids and spermatozoa.…”

Unique thermal behavior of sphingomyelin species with nonhydroxy and 2-hydroxy very-long-chain (C28-C32) PUFAs

“…After collection, the SM these fatty acids ( 5,6 ). Both types of SM species are absent altogether from the testis before puberty, n-V SM appearing before h-V SM after the onset of spermatogenesis ( 6 ).…”

Sphingomyelin metabolism is involved in the differentiation of MDCK cells induced by environmental hypertonicity

“…The bands corresponding to the Rf of the different standards were scraped off and separated from the plate by extraction. This was performed by three successive extractions with chloroform-methanol-water (5:5:1, v/v/v), thoroughly mixing, centrifuging, collecting the solvents, and partitioning with 4 vol of water to recover the lipids in the chloroform phase ( 32 ). This phase was evaporated under N 2 fl ow, and the samples were analyzed by MALDI TOF-TOF analysis at LANAIS-PROEM-CONICET, Argentina.…”