In Utero exposure to genistein enhanced intranasal house dust mite allergen-induced respiratory sensitization in young adult B6C3F1 mice

Abstract

Despite many hypothesized benefits of dietary isoflavone genistein (GEN) deriving from soy-based products, questions surrounding GEN’s developmental immunotoxic effects are increasing. To understand how in utero GEN exposure may modulate postnatal respiratory sensitization, we conducted a time course study using a common household allergen (house dust mites: HDM; 10 μg/mouse) following intranasal instillation, a physiological route of allergen exposure. GEN was administered to dams by gavage from gestational day 14 to parturition at a physiologically relevant dose (20 mg/kg bw). Female and male offspring were sensitized with HDM allergens beginning about one month prior to sacrifice followed by challenges with three weekly doses of HDM extracts, and they were euthanized at day 3 following the final HDM exposure at four different time points (postnatal day (PND) 80, 120, 160, and 200). In utero GEN combined with postnatal HDM exposures (GEN+HDM) increased total IgE production in both young female and male B6C3F1 offspring (e.g., PND 80 in females and PND 120 in males). Increased antigen-specific IgG1, IgG2a and IgG2b levels were also observed at various time points in both female and male offspring. In addition, increases in macrophage number in bronchoalveolar lavage fluid of both female and male GEN+HDM offspring at PND 80 and PND 120, respectively, were observed when compared to the vehicle group. For T cells, an increase over the vehicle in female GEN+HDM offspring was observed at PND 80. Due to similar patterns of increases, it seems likely that GEN+HDM-induced increases in total IgE and macrophages are related. Overall, in utero GEN plus later-life HDM exposures exert increases in total IgE and HDM-specific IgG production as well as macrophage recruitments to the lung in young adult mice.

Biochemistry and use of soybean isoflavones in functional food development

“…The adverse immunomodulating activity of isoflavones is especially damaging to those whose immune systems are immature. This is evidenced by the observation that prenatal and intrauterine exposure to dietary isoflavones can lead to an immunesuppressive effect in the offspring (Gaffer et al 2018) and can cause an increase in the sensitization of the postnatal respiratory tract (Guo and Meng 2016), respectively, thereby resulting in a higher risk of infection and an increased sensitivity to allergens. Follow-up studies to decipher the mechanisms of action of genistein and other soybean isoflavones are, therefore, in dire need.…”

Biomarker Identification of Maternal Genistein Exposure Induced Obesity by Metabonomics Analysis

“…Recently, investigators have been using metabolomics to profile serum or urine in search of biomarkers and to explore the mechanisms of intrauterine chemicals exposure and dis-eases, such as maternal vitamin D supplement and children's vitamin D deficiency, 10) intrauterine lipopolysaccharide exposure and brain injuries in offspring. 11) Additionally, a number of methods are currently used to assess the effect of maternal genistein exposure to their offspring, including epidemiological surveys 12,13) and different animal experiments. [14][15][16] However, none of these tested the changes of metabolism.…”