Collaborative work on evaluation of ovarian toxicity 14) Two- or four-week repeated-dose studies and fertility study of atrazine in female rats

Shibayama, Hiroshi; Kotera, Takashi; Shinoda, Yasuhiko; Hanada, Tomohiko; Kajihara, Tsutomu; Ueda, Makoto; Tamura, Hiro Omi; Ishibashi, Seitarou; Yamashita, Yasuhiro; Ochi, Seishi

doi:10.2131/jts.34.s147

Cited by 28 publications

(15 citation statements)

References 8 publications

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“…In addition, there were no females that presented with this phenotype in the control groups and we have never observed a similar effect in our breeding groups. A previous study exposed female Sprague-Dawley rats to 3, 30, or 300 mg/kg atrazine for two or four weeks reported a prolonged diestrus period, large-sized atretic follicles, and uterine atrophy in the 300 mg/kg treatment group 39 . Furthermore, a study conducted by Gojmerac et al 28 reported that an atrazine exposure of 2 mg/kg in feed for 19 days in adult female pigs caused cystic ovarian degeneration and an increase in the persistence of the corpus luteum 28 .…”

Section: Discussionmentioning

confidence: 86%

An embryonic atrazine exposure results in reproductive dysfunction in adult zebrafish and morphological alterations in their offspring

Wirbisky¹,

Weber²,

Sepúlveda

et al. 2016

Sci Rep

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The herbicide atrazine, a suspected endocrine disrupting chemical (EDC), frequently contaminates potable water supplies. Studies suggest alterations in the neuroendocrine system along the hypothalamus-pituitary-gonadal axis; however, most studies address either developmental, pubertal, or adulthood exposures, with few investigations regarding a developmental origins hypothesis. In this study, zebrafish were exposed to 0, 0.3, 3, or 30 parts per billion (ppb) atrazine through embryogenesis and then allowed to mature with no additional chemical exposure. Reproductive function, histopathology, hormone levels, offspring morphology, and the ovarian transcriptome were assessed. Embryonic atrazine exposure resulted in a significant increase in progesterone levels in the 3 and 30 ppb groups. A significant decrease in spawning and a significant increase in follicular atresia in the 30 ppb group were observed. In offspring, a decrease in the head length to body ratio in the 30 ppb group, along with a significant increase in head width to body ratio in the 0.3 and 3 ppb groups occurred. Transcriptomic alterations involved genes associated with endocrine system development and function, tissue development, and behavior. This study provides evidence to support atrazine as an EDC causing reproductive dysfunction and molecular alterations in adults exposed only during embryogenesis and morphological alterations in their offspring.

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Section: Discussionmentioning

confidence: 86%

An embryonic atrazine exposure results in reproductive dysfunction in adult zebrafish and morphological alterations in their offspring

Wirbisky¹,

Weber²,

Sepúlveda

et al. 2016

Sci Rep

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“…The dose volume was set at 5 ml kg −1 of body weight. The dosage and treatment period were chosen based on previous studies showing adverse effects on the reproductive system [25][26][27][28]. For estrous cycle staging, vaginal smears were collected once or twice a day and classified microscopically as diestrus, proestrus, estrus, or metestrus [29].…”

Section: Methodsmentioning

confidence: 99%

Quantification of steroids and endocrine disrupting chemicals in rat ovaries by LC-MS/MS for reproductive toxicology assessment

et al. 2012

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Reproductive function is controlled by a finely tuned balance of androgens and estrogens. Environmental toxicants, notably endocrine disrupting chemicals (EDCs), appear to be involved in the disruption of hormonal balance in several studies. To further describe the effects of selected EDCs on steroid secretion in female rats, we aim to simultaneously investigate the EDC concentration and the sex hormone balance in the ovaries. Therefore, an effective method has been developed for the quantification of the sex steroid hormones (testosterone, androstenedione, estradiol, and estrone) and four endocrine disrupting chemicals (bisphenol A, atrazine, and the active metabolites of methoxychlor and vinclozolin) in rat ovaries. The sample preparation procedure is based on the so-called "quick, easy, cheap, effective, rugged, and safe" approach, and an analytical method was developed to quantify these compounds with low detection limits by liquid chromatography coupled with a tandem mass spectrometer. This analytical method, applied to rat ovary samples following subacute EDC exposure, revealed some new findings for toxicological evaluation. In particular, we showed that EDCs with the same described in vitro mechanisms of action have different effects on the gonadal steroid balance. These results highlight the need to develop an integrative evaluation with the simultaneous measurement of EDCs and numerous steroids for good risk assessment.

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“… 30 Davis et al (1997), 40 Dodo et al (2009), 82 Ishii et al. (2009), 164 Rehm et al (2007), 175 Shibayama et al (2009), 188 Taketa et al (2011), 214 Yuan and Foley (2002)…”

Section: Morphologymentioning

confidence: 99%

Nonproliferative and Proliferative Lesions of the Rat and Mouse Female Reproductive System

Alison²,

et al. 2014

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The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath.org/inhand.asp) is a joint initiative of the Societies of Toxicological Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in the female reproductive tract of laboratory rats and mice, with color photomicrographs illustrating examples of some lesions. The standardized nomenclature presented in this document is also available electronically on the internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and aging lesions as well as lesions induced by exposure to test materials. There is also a section on normal cyclical changes observed in the ovary, uterus, cervix and vagina to compare normal physiological changes with pathological lesions. A widely accepted and utilized international harmonization of nomenclature for female reproductive tract lesions in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists.

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Collaborative work on evaluation of ovarian toxicity 14) Two- or four-week repeated-dose studies and fertility study of atrazine in female rats

Cited by 28 publications

References 8 publications

An embryonic atrazine exposure results in reproductive dysfunction in adult zebrafish and morphological alterations in their offspring

An embryonic atrazine exposure results in reproductive dysfunction in adult zebrafish and morphological alterations in their offspring

Quantification of steroids and endocrine disrupting chemicals in rat ovaries by LC-MS/MS for reproductive toxicology assessment

Nonproliferative and Proliferative Lesions of the Rat and Mouse Female Reproductive System

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