Exposure to neonicotinoids and serum testosterone in men, women, and children

Neonicotinoids are the most used pesticides in the world and, despite being harmful to honeybees, they are considered safe for mammals. However, they have been associated with decreasing testosterone levels in several experimental animal models. In the present study, we aimed to determine the association of urinary neonicotinoids with serum testosterone in humans. We analyzed data on 2014 male and female participants to the National Health and Nutrition Examination Survey conducted between 2015 and 2016 aged 6 or older. In linear regression adjusted for age and potential confounders, serum total testosterone was 37.78% lower with 10-fold increase in urinary total neonicotinoids (95% CI: -58.82, -6.00), 20.81% lower with 10-fold increase in urinary 5-hydroxy-imidacloprid (95% CI: -34.94, -3.62) and 25.01% lower with 10-fold increase in urinary n-desmethyl-acetamiprid (95% CI: -39.80, -6.58) among males.
Serum free androgen index (FAI) was also decreased with higher urinary n-desmethyl-acetamiprid. In females, serum total testosterone was 32.91% lower with 10-fold increase in urinary total neonicotinoids (95% CI: -54.93, -0.13), 21.32% lower with 10-fold increase in urinary 5-hydroxy-imidacloprid (95% CI: -29.31, -12.42) and 15.42% lower with urinary detection of 5-hydroxy-imidacloprid (95% CI: -22.80, -7.34). FAI was likewise reduced with higher urinary levels of 5-hydroxy-imidacloprid and N-desmethyl-acetamiprid. In conclusion, this study using a sample representative of the US population is the first to report that exposure to neonicotinoids is associated with decreased serum testosterone levels in humans. However, future prospective studies are warranted to confirm these findings.

Circ_FURIN knockdown assuages Testosterone-induced human ovarian granulosa-like tumor cell disorders by sponging miR-423-5p to reduce MTM1 expression in polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among reproductive-age women. The mechanism by which circular RNA (circRNA) drives PCOS development remains unclear. Thus, the study is designed to explore the role of a novel circRNA, circ_FURIN, in the PCOS cell model and the underlying mechanism.
Methods: PCOS cell model was established by treating human ovarian granulosa-like tumor cells (KGN) with Testosterone (TTR). RNA expressions of circ_FURIN, microRNA-423-5p (miR-423-5p) and myotubularin 1 (MTM1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was checked by Western blot. Cell proliferation was investigated by a 5-Ethynyl-29-deoxyuridine assay, 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis for cell cycle. Apoptotic cells were quantified by flow cytometry analysis for cell apoptosis. The interplay between miR-423-5p and circ_FURIN or MTM1 was identified by dual-luciferase reporter and RNA pull-down assays.
Results: Circ_FURIN and MTM1 expressions were significantly upregulated, whereas miR-423-5p was downregulated in the ovarian cortex tissues of PCOS patients and TTR-treated KGN cells compared with controls. Circ_FURIN depletion relieved TTR-induced proliferation inhibition and apoptosis promotion. Besides, knockdown of miR-423-5p, a target miRNA of circ_FURIN, rescued circ_FURIN knockdown-mediated effects under TTR treatment. MiR-423-5p remitted TTR-induced cell disorders by binding to MTM1. Moreover, circ_FURIN modulated MTM1 expression through miR-423-5p.
Conclusion: Circ_FURIN silencing protected against TTR-induced dysfunction by the miR-423-5p/MTM1 pathway in human ovarian granulosa-like tumor cells.

Testosterone Changes in Men With Obesity and Type 2 Diabetes 6 Months After Sleeve Gastrectomy With Transit Bipartition

Background: Metabolic/bariatric surgery has been shown to increase testosterone in males with obesity. This study investigated the effect of the novel metabolic/bariatric surgery procedure, sleeve gastrectomy with transit bipartition (SG-TB), on serum total testosterone and metabolic variable changes in men with obesity and type 2 diabetes.
Methods: In a prospective single-center cohort study, laboratory samples were analyzed preoperatively and at 6 months following SG-TB in patients with a body mass index (BMI) ≥30 kg/m2. Changes in metabolic parameters and testosterone were evaluated.
Results: Between July 2018 and March 2019, 166 patients with a mean baseline BMI of 34.9±3.8 kg/m2 (mean age 51.5±9.3 y), glycosylated hemoglobin 9.5±1.3%, and testosterone 3.1±1.3 underwent SG-TB. At 6-month follow-up, mean excess BMI loss was 70.2±24.3%; glycosylated hemoglobin, 6.6±1.1% (P<0.001); and testosterone, 4.5±1.5 (P<0.001).
Conclusion: In the early term following SG-TB, more than any other factor assessed, BMI loss was found to be a significant driver of improvement in testosterone levels. Regardless of preoperative obesity classification, patients with initially low testosterone attained significantly increased testosterone levels at 6-month follow-up.

Chronic exposure to polystyrene microplastics induced male reproductive toxicity and decreased testosterone levels via the LH-mediated LHR/cAMP/PKA/StAR pathway

Background: Microplastics (MPs), which are smaller in size and difficult to degrade, can be easily ingested by marine life and enter mammals through the food chain. Our previous study demonstrated that following acute exposure to MPs, the serum testosterone content reduced and sperm quality declined, resulting in male reproductive dysfunction in mice. However, the toxic effect of long-term exposure to MPs at environmental exposure levels on the reproductive system of mammals remains unclear.
Results: In vivo, mice were given drinking water containing 100 μg/L and 1000 μg/L polystyrene MPs (PS-MPs) with particle sizes of 0.5 μm, 4 μm, and 10 μm for 180 consecutive days. We observed alterations in testicular morphology and reductions in testosterone, LH and FSH contents in serum. In addition, the viability of sperm was declined and the rate of sperm abnormality was increased following exposure to PS-MPs. The expression of steroidogenic enzymes and StAR was downregulated in testis tissues. In vitro, we used primary Leydig cells to explore the underlying mechanism of the decrease in testosterone induced by PS-MPs. First, we discovered that PS-MPs attached to and became internalized by Leydig cells. And then we found that the contents of testosterone in the supernatant declined. Meanwhile, LHR, steroidogenic enzymes and StAR were downregulated with concentration-dependent on PS-MPs. We also confirmed that PS-MPs decreased StAR expression by inhibiting activation of the AC/cAMP/PKA pathway. Moreover, the overexpression of LHR alleviated the reduction in StAR and steroidogenic enzymes levels, and finally alleviated the reduction in testosterone induced by PS-MPs.
Conclusions: PS-MPs exposure resulted in alterations in testicular histology, abnormal spermatogenesis, and interference of serum hormone secretion in mice. PS-MPs induced a reduction in testosterone level through downregulation of the LH-mediated LHR/cAMP/PKA/StAR pathway. In summary, our study showed that chronic exposure to PS-MPs resulted in toxicity of male reproduction under environmental exposure levels, and these potential risks may ring alarm bells of public health.

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Association of Smoking with the Blood Concentration of 25-Hydroxy Vitamin D and Testosterone at High and Low Altitudes

Purpose: This research examined the association of cigarette smoking and altitude with the blood levels of 25-hydroxy vitamin D, testosterone and carotid artery thickness.
Patients and methods: This comparative cross-sectional study involved 37 non-smokers and 24 smokers from a high-altitude area (≥2245 m above sea level) and 40 smokers and 40 non-smokers from a low-altitude area (39-283 m above sea level). The blood testosterone level was determined spectrophotometrically, and the 25-hydroxy vitamin D concentration was measured by ELISA. The IMT of the right and left carotid arteries was determined using ultrasound imaging.
Results: Smoking notably elevated the thickness of the intima media of the right and left carotid arteries at both high and low altitudes (p ≤ 0.001). Smoking at high altitude was associated with a significant increase in the concentration of 25-hydroxy vitamin D and testosterone, while at low altitude it was associated with a significant decrease in both parameters (p ≤ 0.046).
Conclusion: These contrasting results suggest that future studies should focus on finding out if other biochemical parameters show any significant differences in smokers or/and non-smokers when they are tested at elevated height and sea-level. This indicates that dose modifications of medicines (related to alterations in vitamin D and testosterone levels) should be kept in mind while treating smokers and non-smokers at elevated height above sea level.

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