Glyphosate-containing herbicides are among the most widely-used in the world. Although glyphosate itself is relatively non-toxic, growing evidence suggests that commercial herbicide formulations may lead to increased oxidative stress and mitochondrial inhibition. In order to assess these mechanisms in vivo, we chronically (24h) exposed Caenorhabditis elegans to various concentrations of the glyphosate-containing herbicide TouchDown (TD). Following TD exposure, we evaluated the function of specific mitochondrial electron transport chain complexes. Initial oxygen consumption studies demonstrated inhibition in mid- and high-TD concentration treatment groups compared to controls. Results from tetramethylrhodamine ethyl ester and ATP assays indicated reductions in the proton gradient and ATP levels, respectively. Additional studies were designed to determine whether TD exposure resulted in increased reactive oxygen species (ROS) production. Data from hydrogen peroxide, but not superoxide or hydroxyl radical, assays showed statistically significant increases in this specific ROS. Taken together, these data indicate that exposure of Caenorhabditis elegans to TD leads to mitochondrial inhibition and hydrogen peroxide production.

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a prototypical neurotoxicant used in mice to mimic primary features of PD pathology including striatal dopamine depletion and dopamine neuron loss in the substantia nigra pars compacta (SNc). In the literature, there are several experimental paradigms involving multiple doses of MPTP that are used to elicit dopamine neuron loss. However, a recent study reported that a single low dose caused significant loss of dopamine neurons. Here, we determined the effect of a single intraperitoneal injection of one of three doses of MPTP (0.1, 2 and 20 mg/kg) on dopamine neurons, labeled by tyrosine hydroxylase (TH+), and total neuron number (Nissl+) in the SNc using unbiased stereological counting. Data reveal a significant loss of neurons in the SNc (TH+ and Nissl+−) only in the group treated with 20 mg/kg MPTP. Groups treated with lower dose of MPTP (0.1 and 2 mg/kg) only showed significant loss of TH+ neurons rather than TH+ and Nissl+. Striatal dopamine levels were decreased in the groups treated with 2 and 20 mg/kg MPTP and striatal terminal markers including, TH and the dopamine transporter (DAT), were only decreased in the groups treated with 20 mg/kg MPTP. These data demonstrate that lower doses of MPTP likely result in loss of TH expression rather than actual dopamine neuron loss in the SN. This finding reinforces the need to measure both total neuron number along with TH+ cells in determining dopamine neuron loss.

Glyphosate-based herbicides, such as Touchdown (TD) and Roundup, are among the most heavilyused herbicides in the world. While the active ingredient is generally considered non-toxic, the toxicity resulting from exposure to commercially-sold formulations is less clear. In many cases, cell cultures or various model organisms exposed to glyphosate formulations show toxicity and, in some cases, lethality. Using Caenorhabditis elegans, we assessed potential toxic mechanisms through which a highly-concentrated commercial formulation of TD promotes neurodegeneration. Following a 30-minute treatment, we assayed mitochondrial electron transport chain function and reactive oxygen species (ROS) production. Initial oxygen consumption studies indicated general mitochondrial inhibition compared to controls (*p < 0.05). When Complex II activity was further assessed, inhibition was observed in all TD-treated groups (*p < 0.05). Complex IV activity, however, was not adversely affected by TD. This electron transport chain inhibition also resulted in reduced ATP levels (*p < 0.05). Furthermore, hydrogen peroxide levels, but not other ROS, were increased (*p < 0.05). Taken together, these data indicate that commercially-available formulations of TD may exert neurotoxicity through Complex II (succinate dehydrogenase) inhibition, decreased ATP levels, and increased hydrogen peroxide production.

Existing studies on pregnancy-related outcomes among cancer survivors are limited by sample size or specificity of the cancer type. This study estimated the burden of adverse maternal and fetal outcomes among pregnant cancer survivors using a national database. This study was a retrospective analysis of National Inpatient Sample collected during 2010–2014. Multivariate regression models were used to calculate odds ratios for maternal and fetal outcomes. The study included a weighted sample of 64,506 pregnant cancer survivors and 18,687,217 pregnant women without cancer. Pregnant cancer survivors had significantly higher odds for death during delivery hospitalization, compared to pregnant women without cancer (58 versus 5 deaths per 100,000 pregnancies). They also had higher odds of severe maternal morbidity (aOR 2.00 [95% CI 1.66–2.41]), cesarean section (aOR 1.27 [95% CI 1.19–1.37]), labor induction (aOR 1.17 [95% CI 1.07–1.29]), pre-eclampsia (aOR 1.18 [95% CI 1.02–1.36]), preterm labor (aOR 1.55 [95% CI 1.36–1.76]), chorioamnionitis (aOR 1.45 [95% CI 1.15–1.82]), postpartum infection (aOR 1.68 [95% CI 1.21–2.33]), venous thromboembolism (aOR 3.62 [95% CI 2.69–4.88]), and decreased fetal movements (aOR 1.67 [95% CI 1.13–2.46]). This study showed that pregnancy among cancer survivors constitutes a high-risk condition requiring advanced care and collective efforts from multiple subspecialties.

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