Maternal Exposure Results in Long-Term Deoxynivalenol Persistence in Piglets’ Plasma and Modulates the Immune System

Abstract

Deoxynivalenol (DON)-contaminated feed represents a serious problem for pigs due to their high sensitivity to its toxicological effects. The aim of the present study was to evaluate the impact of intrauterine DON exposure on the immune system of piglets. Pure DON was intravenously administered to sows at the end of gestation (during the last 2–3 days of gestation, one dose of 300 µg per day). The plasma concentration of DON was analyzed using liquid chromatography combined with high-resolution Orbitrap-based mass spectrometry (LC–MS/MS (HR)) and selected immune parameters were monitored six times in piglets from birth to 18 weeks. DON was found in the plasma of 90% of newborn piglets at a mean concentration of 6.28 ng/mL and subsequently, at one, three, and seven weeks after birth with decreasing concentrations. Trace amounts were still present in the plasma 14 weeks after birth. Flow cytometry revealed a significant impact of DON on T lymphocyte subpopulations during the early postnatal period. Lower percentages of regulatory T cells, T helper lymphocytes, and their double positive CD4+CD8+ subset were followed by increased percentages of cytotoxic T lymphocytes and γδ T cells. The capacity to produce pro-inflammatory cytokines was also significantly lower after intrauterine DON exposure. In conclusion, this study revealed a long-term persistence of DON in the plasma of the piglets as a consequence of short-term intrauterine exposure, leading to altered immune parameters.

Exposure to Deoxynivalenol During Pregnancy and Lactation Enhances Food Allergy and Reduces Vaccine Responsiveness in the Offspring in a Mouse Model

“…There was a downregulation of CD25 + Foxp3 + regulatory T cells in the spleen in both allergic and vaccinated mice born to DON-exposed mothers, compared to the offspring of control-fed mothers. A similar decrease in regulatory T cells in the blood leukocytes of piglets was reported after intravenous administration of DON during pregnancy in pigs (27). Regulatory T cells have a prominent role in vaccination responsiveness (53,54) and allergy development (55).…”

“…Administration of 4.42 mg DON/kg diet to pregnant pigs during second half of pregnancy was shown to induce no significant histomorphological changes in the lymphoid organs of the fetuses (40). However, intravenous administration of DON (300 μg in 500 mL of infusion) in pregnant pigs at the end of gestation altered the prevalence of different lymphocyte subtypes in the blood of piglets after birth (27), indicating a disturbed and unbalanced immune system in these animals. The present study is the first to investigate the consequences of developmental immunotoxicity of DON in later stages of life.…”

“…Although immunomodulatory effects of direct exposure to DON are extensively studied (10,(20)(21)(22), information about the immunotoxicity of exposure to DON during pregnancy is scarce (27). Intravenous administration of DON in pregnant pigs at the end of gestation was shown to alter mRNA expression of IFN-g, IL-17, IL-2, and TNF-a, in the blood leukocytes of the piglets, and induce significant decrease in the population of regulatory T cells, and an increase in cytotoxic and gd T cells in blood samples of these piglets, 1-3 weeks after birth (27). These changes indicate a disturbed and unbalanced immune system in piglets of DONexposed mothers after birth.…”

Transfer of Mycotoxins from Lactation Feed to Colostrum of Sows

“…In the only study in which litter performance was controlled [31], when gilts received up to 6.2 mg/kg (from contaminated wheat) in the gestation-lactation diets, no adverse effect was seen on the litter growth as compared to a control diet. Interestingly, the short-term intrauterine exposure of sows to pure DON intravenously administered during gestation induced a long-term persistence of DON in the plasma of the offspring, and caused an alteration in the immune parameters [32]. Nevertheless, the absence of reference values for the toxicity level in newborn pigs, their reduced immunocompetence [33], the risk of the higher ingestion of DON due to continuous milk intake and the potential ingestion of contaminated feed during the entire lactation period by sows, suggested controlling the sow feed frequently, and more research, particularly regarding DON transfer and toxicity in the piglet, is needed.…”

The Effects of Mycotoxins on Pregnancy and Immune Development

“…Considering the increasing evidence supporting the significant role of immunotoxins in the development of non-communicable diseases [91], studying the exact mechanisms involved in immune effects of mycotoxins, as well as their long-term consequences is crucial.…”