Effects of the mycotoxin deoxynivalenol on steroidogenesis and apoptosis in granulosa cells.
Mycotoxins can reduce fertility and development in livestock, notably in pigs and poultry, although the effect of most mycotoxins on reproductive function in cattle has not been established. One major mycotoxin, deoxynivalenol (DON), not only targets immune cells and activates the ribotoxic stress response (RSR) involving MAPK activation, but also inhibits oocyte maturation in pigs. In this study, we determined the effect of DON on bovine granulosa cell function using a serum-free culture system. Addition of DON inhibited estradiol and progesterone secretion, and reduced levels of mRNA encoding estrogenic (CYP19A1) but not progestogenic (CYP11A1 and STAR) proteins. Cell apoptosis was increased by DON, which also increased FASLG mRNA levels. The mechanism of action of DON was assessed by western blotting and PCR experiments. Addition of DON rapidly and transiently increased phosphorylation of MAPK3/1, and resulted in a more prolonged phosphorylation of MAPK14 (p38) and MAPK8 (JNK). Activation of these pathways by DON resulted in time- and dose-dependent increases in abundance of mRNA encoding the transcription factors FOS, FOSL1, EGR1, and EGR3. We conclude that DON is deleterious to granulosa cell function and acts through a RSR pathway.
Faculté de médecine vétérinaireCentre de recherche en reproduction animale, Université de Montréal, St-Hyacinthe, Quebec, Canada J2S 7C6.
Hilda M
HM
Guerrero-Netro
Faculté de médecine vétérinaireCentre de recherche en reproduction animale, Université de Montréal, St-Hyacinthe, Quebec, Canada J2S 7C6.
Younès
Y
Chorfi
Faculté de médecine vétérinaireCentre de recherche en reproduction animale, Université de Montréal, St-Hyacinthe, Quebec, Canada J2S 7C6 christopher.price@umontreal.ca.
Christopher A
CA
Price
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011374:Progesterone / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D014255:Trichothecenes / Q000494:pharmacology*; D000098682:Steroidogenic Acute Regulatory Protein
D010750:Phosphoproteins; D014255:Trichothecenes; D000098682:Steroidogenic Acute Regulatory Protein; D011374:Progesterone; D004958:Estradiol; D002786:Cholesterol Side-Chain Cleavage Enzyme; C007262:deoxynivalenol