The effects of mono-(2-ethylhexyl)-phthalate on rat Sertoli cell-enriched primary cultures.
There is considerable evidence from in vivo studies that the Sertoli cell is an initial target cell for the actions of phthalates in the rodent testis. Because this metabolically active cell type plays a central role in spermatogenesis, we examined the effects of a toxic phthalate, mono-(2-ethylhexyl)-phthalate (MEHP), on the secretory and synthetic activities of primary testicular cell cultures isolated from 18-day-old rats. These cultures were 78-84% Sertoli cells. Exposure to MEHP decreased cellular ATP by ca. 20%, decreased production of radiolabeled 14CO2 from acetate, and decreased media levels of pyruvate, while it increased media levels of lactate and intracellular lipid. Protein synthesis, evaluated by radiolabeled leucine incorporation, was not affected by MEHP. Mitochondrial succinate dehydrogenase activity was decreased in the presence of MEHP. Michaelis-Menton kinetic analysis indicated this was a mixed inhibition. There was no apparent change in mitochondrial Rhodamine 123 uptake. These data are consistent with the concept that mitochondria are one target for the actions of MEHP in the Sertoli cell.
Chapin
R E
RE
National Institute of Environmental Health Sciences, National Toxicology Program, Research Triangle Park, North Carolina 27709.
Gray
T J
TJ
Phelps
J L
JL
Dutton
S L
SL
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D002478:Cells, Cultured; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006072:Gossypol / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D010795:Phthalic Acids / Q000633:toxicity*; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D011916:Rats, Inbred F344; D012708:Sertoli Cells / Q000187:drug effects*; D013385:Succinate Dehydrogenase / Q000032:analysis
D010795:Phthalic Acids; D011773:Pyruvates; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D004051:Diethylhexyl Phthalate; D013385:Succinate Dehydrogenase; C016599:mono-(2-ethylhexyl)phthalate; D006072:Gossypol