Effects of oxidative stress and inhibitors of the pentose phosphate pathway on sexually dimorphic production of IFN-tau by bovine blastocysts.
Bovine interferon-tau (IFN-tau), the anti-luteolytic factor secreted by conceptuses of pecoran ruminants, is a product of autosomal genes, yet in vitro produced (IVP) female expanded blastocysts (EB) secrete about twice as much IFN-tau as males. Two possible explanations have been tested here. One is that embryos of one sex are differentially susceptible to oxidative stress. The second is that female EB produce more IFN-tau because pentose-phosphate pathway (PPP) activity is elevated as a result of delayed X-chromosome inactivation. IVP bovine zygotes were cultured to the 8-cell stage and placed under conditions designed either to promote oxidative stress (+/-H2O2; 20 vs. 5% O2), or to inhibit glucose 6-phosphate dehydrogenase (G6PDH) activity (addition of dehydroepiandrosterone, DHEA or 6-aminonicotinamide, 6-AN to the medium). At day 8, blastocysts were cultured individually for a further 48 hr to assess IFN-tau production, and embryo sex determined retrospectively. Blastocyst numbers were reduced (P < 0.05) and their continued development impaired (P < 0.05) in presence of H2O2 (200 microM) and 20% O2, but neither IFN-tau production nor sexually dimorphic expression of IFN-tau were affected. IFN-tau production was reduced, particularly in females (P < 0.05), and sexual dimorphic differences in production were lost in the presence of both DHEA (100 microM) and 6-AN (1 microM). In the case of 6-AN, these effects were achieved without a significant decline in blastocyst developmental progression, quality, or cell number. The data suggest that the higher production of IFN-tau by female EB is an indirect outcome of the increased activity of the oxidative arm of the PPP pathway.
Kimura
K
K
Department of Animal Sciences, University of Missouri, Columbia, Missouri, USA. kimurak@affrc.go.jp
Spate
L D
LD
Green
M P
MP
Roberts
R M
RM
D015120:6-Aminonicotinamide / Q000494:pharmacology; D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004303:Dosage Compensation, Genetic; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007370:Interferon Type I / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology; D010427:Pentose Phosphate Pathway / Q000187:drug effects*; D011257:Pregnancy Proteins / Q000096:biosynthesis / Q000378:metabolism*; D012727:Sex Characteristics; D012744:Sex Ratio; D013997:Time Factors
D007370:Interferon Type I; D011257:Pregnancy Proteins; C020947:interferon tau; D015120:6-Aminonicotinamide; D003687:Dehydroepiandrosterone; D006861:Hydrogen Peroxide; D005954:Glucosephosphate Dehydrogenase; D010100:Oxygen