Comparative steroidogenic effects of hexafluoropropylene oxide trimer acid (HFPO-TA) and perfluorooctanoic acid (PFOA): Regulation of histone modifications.

As a widely used alternative to perfluorooctanoic acid (PFOA), hexafluoropropylene oxide trimer acid (HFPO-TA) has been detected in the environment and humans; however, little is known regarding its male reproductive toxicity. To compare the effects of HFPO-TA on steroid hormone synthesis with PFOA, we exposed Leydig cells (MLTC-1) to non-lethal doses (0.1, 1, and 10 µM) of PFOA and HFPO-TA for 48 h. It was found that the levels of steroid hormones, 17α-hydroxyprogesterone (OHP), androstenedione (ASD), and testosterone (T) were significantly increased in 1 and 10 µM of PFOA and HFPO-TA groups, with greater elevation being observed in the HFPO-TA groups than in the PFOA groups at 10 µM. We further showed that the two rate-limiting steroidogenic genes (Star and Cyp11a1) were up-regulated, while Hsd3b, Cyp17a1, and Hsd17b were down-regulated or unchanged after PFOA/HFPO-TA exposure. Moreover, PFOA exposure significantly up-regulated histone H3K4me1/3 and H3K9me1, while down-regulated H3K4me2 and H3K9me2/3 levels. By contrast, H3K4me2/3 and H3K9me2/3 were enhanced, while H3K4me1 and H3K9me1 were repressed after HFPO-TA treatment. It was further confirmed that H3K4me1/3 were increased and H3K9me2 was decreased in Star and Cyp11a1 promoters by PFOA, while HFPO-TA increased H3K4me2/3 and decreased H3K9me1 in the two gene promoters. Therefore, we propose that low levels of PFOA/HFPO-TA enhance the expression of Star and Cyp11a1 by regulating H3K4 and H3K9 methylation, thus stimulating the production of steroid hormones in MLTC-1 cells. Collectively, HFPO-TA exhibits stronger effects on steroidogenesis compared to PFOA, which may be ascribed to the distinct regulation of histone modifications. These data suggest that HFPO-TA does not appear to be a safer alternative to PFOA on the aspect of male reproductive toxicity.

Genome-wide association studies identifies genetic loci related to fatty acid and branched-chain amino acid metabolism and histone modifications under varying nitrogen treatments in safflower (Carthamus tinctorius).

Effective identification and usage of genetic variation are prerequisites for developing nutrient-efficient cultivars. A collection of 94 safflower (Carthamus tinctorius ) genotypes (G) was investigated for important morphological and photosynthetic traits at four nitrogen (N) treatments. We found significant variation for all the studied traits except chlorophyll b (chl b ) among safflower genotypes, nitrogen treatments and G×N interaction. The examined traits showed a 2.82-50.00% increase in response to N application. Biological yield (BY) reflected a significantly positive correlation with fresh shoot weight (FSW), root length (RL), fresh root weight (FRW) and number of leaves (NOL), while a significantly positive correlation was also observed among carotenoids (C), chlorophyll a (chl a ), chl b and total chlorophyll content (CT) under all treatments. Superior genotypes with respect to plant height (PH), FSW, NOL, RL, FRW and BY were clustered into Group 3, while genotypes with better mean performance regarding chl a , chl b C and CT were clustered into Group 2 as observed in principal component analysis. The identified eight best-performing genotypes could be useful to develop improved nitrogen efficient cultivars. Genome-wide association analysis resulted in 32 marker-trait associations (MTAs) under four treatments. Markers namely DArT-45481731 , DArT-17812864 , DArT-15670279 and DArT-45482737 were found consistent. Protein-protein interaction networks of loci associated with MTAs were related to fatty acid and branched-chain amino acid metabolism and histone modifications.