Environmental/industrial toxicants and testicular injury. Final performance report.
Division of Biology and Medicine, Brown University, Providence, Rhode Island 1988 Sep; :1-8
Efforts to determine a pathogenetic sequence for testicular injury following 2,5-hexanedione (110134) intoxication were reported. The research was divided into five specific aims: to use a gamma- diketone treatment protocol to specifically correlate the temporal onset and development of testicular microtubule alterations with the appearance of testicular atrophy; to evaluate the reversibility of 2,5-hexanedione induced testicular atrophy in conjunction with biochemical resolution of the microtubule abnormalities; to investigate the consequences for cells and tissues, particularly Sertoli cells and germ cells in the testis, of microtubule dysfunction caused by intoxication; to delineate the chemistry and biochemistry of the tubulin modification which results in abnormal microtubule assembly kinetics; and to determine the generality of the hypothesis relating microtubule abnormalities with testicular atrophy by testing microtubule properties in testicular atrophy induced by additional gamma-diketones, the acrylamides and carbon- disulfide. A conceptualization of the pathogenetic sequence beginning with 2,5-hexanedione modification of tubulin consisted of the following: tubulin crosslinking leading to microtubule assembly alteration leading to shorter and more numerous microtubules, loss of sertoli cell cytoskeletal integrity, and altered microtubule associated proteins (MAPs) leading to germ cell sloughing and necrosis followed by irreversible germ cell loss. The presence of tubulin crosslinking and microtubule assembly alterations in the testes of 2,5-hexanedione intoxicated rats was documented. Changes in MAPs were noted early during intoxication. MAP changes may impact on vesicle transport and microtubule attachment to adjacent cytoskeletal elements such as intermediate filaments.
NIOSH-Grant; Reproductive-system-disorders; Laboratory-animals; Irritants; Ketones; Testes; Toxic-effects
Pathology and Lab Medicine Div. of Biology and Medicine Brown University, Box G Providence, RI 02912
Final Grant Report
NTIS Accession No.
Division of Biology and Medicine, Brown University, Providence, Rhode Island
Brown University, Providence, Rhode Island