Early Life Exposure to Aflatoxin B1 in Rats: Alterations in Lipids, Hormones, and DNA Methylation among the Offspring

Abstract

Aflatoxins are toxic compounds produced by molds of the Aspergillus species that contaminate food primarily in tropical countries. The most toxic aflatoxin, aflatoxin B1 (AFB1), is a major cause of hepatocellular carcinoma (HCC) in these countries. In sub-Saharan Africa, aflatoxin contamination is common, and perinatal AFB1 exposure has been linked to the early onset of HCC. Epigenetic programming, including changes to DNA methylation, is one mechanism by which early life exposures can lead to adult disease. This study aims to elucidate whether perinatal AFB1 exposure alters markers of offspring health including weight, lipid, and hormone profiles as well as epigenetic regulation that may later influence cancer risk. Pregnant rats were exposed to two doses of AFB1 (low 0.5 and high 5 mg/kg) before conception, throughout pregnancy, and while weaning and compared to an unexposed group. Offspring from each group were followed to 3 weeks or 3 months of age, and their blood and liver samples were collected. Body weights and lipids were assessed at 3 weeks and 3 months while reproductive, gonadotropic, and thyroid hormones were assessed at 3 months. Prenatal AFB1 (high dose) exposure resulted in significant 16.3%, 31.6%, and 7.5% decreases in weight of the offspring at birth, 3 weeks, and 3 months, respectively. Both doses of exposure altered lipid and hormone profiles. Pyrosequencing was used to quantify percent DNA methylation at tumor suppressor gene Tp53 and growth-regulator H19 in DNA from liver and blood. Results were compared between the control and AFB1 exposure groups in 3-week liver samples and 3-week and 3-month blood samples. Relative to controls, Tp53 DNA methylation in both low- and high-dose exposed rats was significantly decreased in liver samples and increased in the blood (p < 0.05 in linear mixed models). H19 methylation was higher in the liver from low- and high-exposed rats and decreased in 3-month blood samples from the high exposure group (p < 0.05). Further research is warranted to determine whether such hormone, lipid, and epigenetic alterations from AFB1 exposure early in life play a role in the development of early-onset HCC.

The Role of Acsl1 and Aldh2 in the Increased Risk for Liver Cancer in Offspring of Obese Mothers

“…Wankhade et al have shown that this altered gut microbiome in offspring of obese mothers in turn leads to metabolic changes in the offspring (18). Furthermore, several groups have shown that epigenetic changes that happen during the fetal development are passed on from parents to the offspring and modulate the risk for cancer (19)(20)(21). It is likely that these factors also play an important role in the increased risk for HCC in the offspring of obese mothers, besides the regulation of gene expression through specific microRNAs.…”

Firefighting, per‐ and polyfluoroalkyl substances, and DNA methylation of genes associated with prostate cancer risk

“…Polymerase chain reaction was used to amplify the region in bisulfite‐converted DNA (15 min at 95°C then [45 cycles × (95°C for 30 s, 43°C for 30 s, 72°C for 1 min)] then 72°C for 10 min). The product was sequenced with a PyroMark Q96 ID according to the procedure previously outlined (Ferrari et al, 2019; Rotimi et al, 2021). Methylation data for three CpG sites on the Alu elements were obtained.…”

Research progress in toxicological effects and mechanism of aflatoxin B1 toxin

“…Prenatal exposure to AFB 1 reduces the body weight of neonatal rats, disrupts lipid and hormone levels, and affect the methylation levels of p53 and growth-regulator H19 in the liver and serum. The pathological changes may increase the risk of HCC in the offspring ( Rotimi et al, 2021 ). These studies indicate that exposure of sexually mature animals to AFB 1 affects gamete production, gamete quality, and gamete maturation, and AFB 1 also disrupts embryonic development, posing a long-term health threat to both pregnant animal mothers and offspring.…”