Effect of conazole fungicides on reproductive development in the female rat

Contemporary American and European girls experience breast development at earlier ages compared with 15-20 years ago. Alterations in BMI alone cannot account for these changes. Several currently used pesticides possess endocrine disrupting properties and may interfere with reproductive development, but human data are sparse. We examined girls whose mothers worked in greenhouses in the first trimester of pregnancy to assess the long-term effects of prenatal pesticide exposure on puberty. Mothers were prenatally categorized as exposed or unexposed to pesticides. We studied the offspring of these greenhouse workers, and evaluated the anthropometry, pubertal staging in the girls, and blood samples were drawn at 3 months of age (n = 90) and again once at school age (6-11 years, n = 83). No clinical and biochemical differences were found between the exposed and unexposed girls at 3 months of age. Mean onset of B2+ was 8.9 years (95% CI: 8.2; 9.7) in prenatally exposed girls, compared with 10.4 years (9.2; 17.6) in the unexposed (p = 0.05), and 10.0 (9.7-10.3) years in a Danish reference population (p = 0.001). Exposed girls had higher serum androstenedione levels (geometric means: 0.58 vs. 0.79 nmol/L, p = 0.046) and lower Anti-Müllerian Hormone (AMH) compared with the unexposed (geometric means: 16.4 vs. 21.3 pmol/L, p > 0.05) and the reference group (20.2 pmol/L, p = 0.012). Levels of testosterone, estradiol, prolactin, FSH, LH, SHBG, DHEAS, DHT, Inhibin A and Inhibin B did not differ between the groups. In conclusion, our findings suggest that prenatal exposure to currently approved pesticides may cause earlier breast development in girls. This association appeared not to be because of changes in gonadotropins, but rather to higher androgen levels, which indirectly may increase oestrogens through aromatization. In addition, lower serum AMH levels indicated a reduced pool of antral ovarian follicles. The long-term consequences of our findings with regard to establishment of future reproductive function still remain unknown.

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“…, 2002; Taxvig et al. , 2007) resulting in adverse reproductive effects in rats after foetal exposure (Rockett et al. , 2006; Blystone et al.…”

Section: Discussionmentioning

confidence: 99%

Early breast development in girls after prenatal exposure to non‐persistent pesticides

et al. 2012

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“…The in vivo findings suggest that prochloraz, ketoconazole, and tebuconazole mainly affect male reproductive health endpoints -effects that conceivably are mediated by reduced testosterone during gestation. the findings on epoxiconazole and propiconazole indicate that they mainly affect female reproductive health, e.g., disruption of estrous cycle (Rockett et al, 2006) and time until vaginal opening (de Castro and Maia, 2012) defining the onset of puberty in female rats (Firlit and Schwartz, 1977). These two conazoles also show a weak estrogenic response in vitro in the MCF-7 cell proliferation assay (data not included in tab.…”

Section: Steroidogenesismentioning

confidence: 99%

Predictive value of cell assays for developmental toxicity and embryotoxicity of conazole fungicides

Dreisig

2013

ALTEX

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“…A metabolite (triazole acetic acid) which is sometimes found in plants treated with conazole pesticides was also added to the list. The analysed conazole substances, their effect on reproductive toxicity parameters and information about the current official and proposed classifications are listed in Table 2; some additional data on reproductive effects from sources other than EFSA, EPA and JMPR are listed in references [87][88][89][90].…”

Section: Datamentioning

confidence: 99%

Assessing the reproductive toxicity of some (con)azole compounds using a structure–activity relationship approach

Bolčič-Tavčar

Vračko

2009

SAR and QSAR in Environmental Research

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The present research investigates the study of a set of 27 (con)azoles and their reproductive toxicity. (Con)azoles are used as fungicides and herbicides in agriculture for treatment of fruits, vegetables, cereals, and seeds, or as human antimycotic therapeutics. According to EEC Directive 91/414, active substances used in plant protection products must undergo reproductive toxicity testing. Reproductive toxicity is a complex biological endpoint, which includes many different biological processes and, therefore, it can only to a limited extent be assessed by a single quantitative structure-activity relationship (QSAR) model. The proposed SAR models are built using unsupervised methods, such as hierarchical clustering, principal component analysis and self-organizing maps, with the aim of studying the similarity relationships between structures. The molecular structures are represented with a set of topological and structural descriptors. The models showing clusters, closest neighbours or outliers may support the categorization and the classification of (con)azoles as potential reproductive toxicants.

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Effect of conazole fungicides on reproductive development in the female rat

Cited by 64 publications

References 38 publications

Early breast development in girls after prenatal exposure to non‐persistent pesticides

Early breast development in girls after prenatal exposure to non‐persistent pesticides

Predictive value of cell assays for developmental toxicity and embryotoxicity of conazole fungicides

Assessing the reproductive toxicity of some (con)azole compounds using a structure–activity relationship approach

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