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Endocrine-active chemicals can directly act on nuclear receptors and trigger the disturbances of metabolism and a homeostatic system, which are important risk factors for complicating chronic diseases in humans. The endocrine-active potentials of pesticides acting on estrogen, androgen, and thyroid hormone receptors have been extensively evaluated for pesticides; however, the effects on other receptors are less understood. This study aims to comprehensively characterize and prioritize the endocrine-active pesticides using an exposure-activity ratio (EAR) method and toxicological prioritization index (ToxPi). The aggregate exposure assessment of pesticides was performed using a computational exposure model [stochastic human exposure and dose simulation high-throughput model (SHEDS-HT)]. Minimum in vitro point of departure values were converted to human oral equivalent doses via in vitro -to- in vivo extrapolation. The overall endocrine-disrupting potentials of pesticides were evaluated via 76 assays, representing 11 nuclear receptors. EARs and ToxPi scores were then derived to prioritize 79 pesticides in food. This case study demonstrates that EAR profiling can inform the regulatory agencies for a relevant chemical prioritization, which would direct in-depth health risk assessments in the future.

Neonicotinoids are the most widely used insecticides in modern agriculture, and their residues have been found in the environment and food. Previous studies reported that neonicotinoids exert toxic effects in various tissues, but whether they interfered with the female reproductive process remains unknown. In our present research, thiamethoxam was selected as a representative neonicotinoid to establish a mouse toxicity model with gavage. We found that thiamethoxam decreased the ovarian coefficient and disrupted the expression of female hormone receptors, subsequently affecting follicle development. Ovarian granulosa cells from the thiamethoxam exposure group underwent a high level of apoptosis. Using transcriptome analysis, we showed that thiamethoxam exposure altered the expression of multiple oocyte genes related to inflammation, apoptosis, and endoplasmic reticulum stress. Thiamethoxam also adversely affected oocyte and embryo development. Western blotting and fluorescence staining results confirmed that thiamethoxam affected the integrity of DNA, triggered apoptosis, promoted oxidative stress and endoplasmic reticulum stress, and impaired mitochondrial function. Collectively, our results indicated that thiamethoxam exposure disrupts ovarian homeostasis and decreases oocyte quality via endoplasmic reticulum stress and apoptosis induction.

Cardiovascular disease (CVD) is the leading cause of death in the United States, and hypercholesterolemia is a major risk factor. Population studies, as well as animal and intervention studies, support the consumption of a variety of vegetables as a means to reduce CVD risk through modulation of hypercholesterolemia. Microgreens of a variety of vegetables and herbs have been reported to be more nutrient dense compared to their mature counterparts. However, little is known about the effectiveness of microgreens in affecting lipid and cholesterol levels. The present study used a rodent diet-induced obesity (DIO) model to address this question. C57BL/6NCr mice (n = 60, male, 5 weeks old) were randomly assigned to six feeding groups: (1) low-fat diet; (2) high-fat diet; (3) low-fat diet + 1.09% red cabbage microgreens; (4) low-fat diet + 1.66% mature red cabbage; (5) high-fat diet + 1.09% red cabbage microgreens; (6) high-fat diet + 1.66% mature red cabbage. The animals were on their respective diets for 8 weeks. We found microgreen supplementation attenuated high-fat diet induced weight gain. Moreover, supplementation with microgreens significantly lowered circulating LDL levels in animals fed the high-fat diet and reduced hepatic cholesterol ester, triacylglycerol levels, and expression of inflammatory cytokines in the liver. These data suggest that microgreens can modulate weight gain and cholesterol metabolism and may protect against CVD by preventing hypercholesterolemia.