Understanding the Toxin Effects of β-Zearalenol and HT-2 on Bovine Granulosa Cells Using iTRAQ-Based Proteomics

Abstract

Zearalenone (ZEA) and T-2 are the most common mycotoxins in grains and can enter the animal and human food-chain and cause many health disorders. To elucidate the toxic response profile, we stimulated bovine granulosa cells (GCs) with β-zearalenol or HT-2. Using isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic, 178 and 291 differentially expressed proteins (DEPs, fold change ≥ 1.3 and p-value < 0.05) in β-zearalenol and HT-2 groups were identified, respectively. Among these DEPs, there were 66 common DEPs between β-zearalenol and HT-2 groups. These 66 DEPs were associated with 23 biological processes terms, 14 molecular functions terms, and 19 cellular components terms. Most heat shock proteins (HSPs) were involved in the toxic response. Reactive oxygen species accumulation, the endoplasmic reticulum (ER)-stress related marker molecule (GRP78), and apoptosis were activated. β-zearalenol and HT-2 inhibited oestradiol (E2) production. These results emphasized the important function of HSPs, clarified oxidative stress, and demonstrated the caspase-3 signaling cascade involved in mycotoxin-treated toxic response, along with decreased E2 production. This study offers new insights into the toxicity of β-zearalenol and HT-2 on ovarian granulosa cells.

Adverse Effects of Fusarium Toxins in Ruminants: A Review of In Vivo and In Vitro Studies

“…Bovine granulosa cells were exposed in vitro to 0.09 and 3.1 µM α-ZEL and presented a decrease in the synthesis of estradiol and progesterone, respectively, whereas exposure to β-ZEL at the same concentrations did not affect cell function [169]. At a higher concentration of 25 µM, β-ZEL was able to induce endoplasmic stress in granulosa cells with a subsequent decrease in the estradiol secretion [185]. These authors observed a similar behavior when bovine granulosa cells were exposed to 50 nM HT-2 toxin, the metabolite from the T-2 toxin.…”

“…Granulosa cells are used as species-specific models to evaluate the effects of toxins on steroidogenesis, oxidative stress, and apoptosis. In cattle, most cells are collected from small ovarian follicles (1-7 mm) [169,185,186], whereas one study was performed with granulosa cells harvested from large follicles (8-22 mm) [187]. It was noteworthy that granulosa cells from large follicles are less sensitive to mycotoxin exposure than those from small follicles.…”

“…These authors observed a similar behavior when bovine granulosa cells were exposed to 50 nM HT-2 toxin, the metabolite from the T-2 toxin. Although the T-2 toxin does not disturb specifically the hormonal homeostasis, this mycotoxin and its metabolite HT-2 cause apoptosis and induce oxidative stress in different cell types, including those involved in the reproductive function [185,186].…”

Practical Application of Urinary Zearalenone Monitoring System for Feed Hygiene Management of a Japanese Black Cattle Breeding Herd—The Relationship between Monthly Anti-Müllerian Hormone and Serum Amyloid A Concentrations

“…The second purpose of the present study was to evaluate both ZEN (Fusarium mycotoxin called pre-harvest mycotoxin) and STC (Aspergillus mycotoxin called post-harvest mycotoxin) dynamics in the dietary roughage (rice straw and WCS) using the naturally ZEN (also STC)-contaminated herd (Herd C) detected in August 2019 as a model/examined herd, mainly by urinary ZEN monitoring during the year from July 2020 to June 2021. In addition, ZEN and its metabolites have been suggested to cause apoptosis of granulosa cell/atresia of follicles in several animals [27][28][29][30], the relationship between urinary ZEN and AMH concentration during the monitoring period was studied to clarify the effects of ZEN exposure on AMH secretion from antral follicles. In this regard, similar to our recently reported decrease in AMH concentration during the peripartum period [19], all five examined JB cows displayed a clear decline in AMH concentrations in the month of their calving with a large range of SAA concentrations (Cow 1: 3.1 mg/L, Cow 2: 23.4 mg/L, Cow 3: 4.9 mg/L, and Cow 5: 2.9 mg/L; data not shown).…”

Using historical museum samples to examine divergent and parallel evolution in the invasive starling

“…Of the genes that have possibly undergone parallel selection in both the native and invasive range, we see a number of these genes which have been previously associated with responses to various pollutants. Exposure to HT-2, a grain mycotoxin, has been shown to downregulate nidogen 2 (NID2) expression in bovines (Li et al 2020a). Starling interaction with livestock is well documented, and indeed is a key motivating factor of their management in agricultural areas (Linz et al 2007).…”