Mycotoxin Fumonisin B1 Interferes Sphingolipid Metabolisms and Neural Tube Closure during Early Embryogenesis in Brown Tsaiya Ducks

Abstract

Fumonisin B1 (FB1) is among the most common contaminants produced by Fusarium spp. fungus from corns and animal feeds. Although FB1 has been known to cause physical or functional defects of embryos in humans and several animal species such as Syrian hamsters, rabbits, and rodents, little is known about the precise toxicity to the embryos and the underlying mechanisms have not been fully addressed. The present study aimed to investigate its developmental toxicity and potential mechanisms of action on sphingolipid metabolism in Brown Tsaiya Ducks (BTDs) embryos. We examined the effect of various FB1 dosages (0, 10, 20 and 40 µg/embryo) on BTD embryogenesis 72 h post-incubation. The sphingomyelin content of duck embryos decreased (P < 0.05) in the highest FB1-treated group (40 µg). Failure of neural tube closure was observed in treated embryos and the expression levels of a neurulation-related gene, sonic hedgehog (Shh) was abnormally decreased. The sphingolipid metabolism-related genes including N-acylsphingosine amidohydrolase 1 (ASAH1), and ceramide synthase 6 (CERS6) expressions were altered in the treated embryos compared to those in the control embryos. Apparently, FB1 have interfered sphingolipid metabolisms by inhibiting the functions of ceramide synthase and folate transporters. In conclusion, FB1-caused developmental retardation and abnormalities, such as neural tube defects in Brown Tsaiya Duck embryos, as well as are partly mediated by the disruption of sphingolipid metabolisms.

Targeted Analysis of Sphingolipids in Turkeys Fed Fusariotoxins: First Evidence of Key Changes That Could Help Explain Their Relative Resistance to Fumonisin Toxicity

“…Sphingomyelins tended to decrease in the liver of pigs administered FB1 orally at a dose equivalent to 25–30 mg/kg of feed, and moderate signs of toxicity were observed at this dose [ 28 ]. A reduction in sphingomyelin concentrations at cytotoxic doses of FB1 was also observed after the direct administration of FB1 to Brown Tsaiya duck embryos [ 63 ], and in cell cultures at concentrations of 20 to 250 µM of FB1 [ 20 , 21 , 22 ]. Moreover, the role of sphingomyelin in FB1-induced toxicity has been observed in mice using myriocin, which is a specific inhibitor of serine palmitoyltransferase ( Figure 1 ).…”

“…Even if little is known about CerS in avian species, recent studies on Brown Tsaiya ducks suggest that the enzymes involved in the synthesis of sphingolipids were the same as those reported in mammals [ 63 ]. CerS2, and to a lesser extent CerS4 and CerS5, are most abundant in the liver and are responsible for the synthesis of, respectively, C20-C26, C18-C20, and C14-C16 ceramides ( Figure 1 ) [ 12 ].…”

Can Red Yeast (Sporidiobolus pararoseus) Be Used as a Novel Feed Additive for Mycotoxin Binders in Broiler Chickens?

“…In general, the signs of toxicity from mycotoxins in animals include them exhibiting a decreased level of production, weight, feed conversion, and feed intake, increased levels of bloody diarrhea, severe dermatitis, hemorrhages, and an increased death rate [ 5 , 12 ]. Furthermore, this causes reproductive problems and developmental toxicity in poultry and histopathological changes in the kidneys and liver [ 6 , 14 , 15 ]. Moreover, mycotoxins that are produced by the Fusarium spp.…”

Protocatechuic acid: A novel detoxication agent of fumonisin B1 for poultry industry

“…Fumonisins (FBs) are nonfluorescent, water-soluble, and heat-stable mycotoxins produced by Fusarium (verticillioides, proliferatum, anthophilum, dlamini, fujikuroi, globosum, napiforme, nyagamai, oxysporum) and Aspergillus (awamori, niger) fungi. They primarily contaminate corn (maize), cornderived products, asparagus, sorghum, beer, rice, soybeans, and animal feed, as well as the food chain, threatening to food safety and minimizing animal production (1)(2)(3)(4). According to recent estimates, 60-80% of mycotoxin contamination occurs naturally in food and feed, posing a risk to human and animal health worldwide (5).…”

“…They can also enter every stage of the food chain and food handling via a contaminated source ( 1 , 6 ). The B-series of FBs are the most common contamination, with FB1 being the most prevalent (70–80%) followed by FB2 and FB3, causing neurotoxicity, hepatotoxicity, nephrotoxicity, immunotoxicity, and embryotoxicity in both animals and humans ( 2 , 3 , 5 ). FB1 induces atherosclerosis in monkeys, porcine pulmonary edema (PPE) syndrome and hydrothorax in pigs, hepatic and renal damage and immunosuppression in poultry, equine leuko-encephalomalacia (ELEM) in horses, and kidney and renal cancer in rodents, as well as primary liver cancer, esophageal cancer, neural tube defects (NTDs), and idiopathic congestive cardiopathy (ICC) in humans ( 7 – 9 ).…”