Effects of prenatal exposure to a low dose atrazine metabolite mixture on pubertal timing and prostate development of male Long-Evans rats.

The present study examines the postnatal reproductive development of male rats following prenatal exposure to an atrazine metabolite mixture (AMM) consisting of the herbicide atrazine and its environmental metabolites diaminochlorotriazine, hydroxyatrazine, deethylatrazine, and deisopropylatrazine. Pregnant Long-Evans rats were treated by gavage with 0.09, 0.87, or 8.73mg AMM/kg body weight (BW), vehicle, or 100mg ATR/kg BW positive control, on gestation days 15-19. Preputial separation was significantly delayed in 0.87 mg and 8.73mg AMM-exposed males. AMM-exposed males demonstrated a significant treatment-related increase in incidence and severity of inflammation in the prostate on postnatal day (PND) 120. A dose-dependent increase in epididymal fat masses and prostate foci were grossly visible in AMM-exposed offspring. These results indicate that a short, late prenatal exposure to mixture of chlorotriazine metabolites can cause chronic prostatitis in male LE rats. The mode of action for these effects is presently unclear.

[1]  R. Cooper,et al.  The effects of atrazine metabolites on puberty and thyroid function in the male Wistar rat. , 2002, Toxicological sciences : an official journal of the Society of Toxicology.

[2]  Douglas C Wolf,et al.  Atrazine-induced reproductive tract alterations after transplacental and/or lactational exposure in male Long-Evans rats. , 2007, Toxicology and applied pharmacology.

[3]  R. Cooper,et al.  Maternal exposure to atrazine during lactation suppresses suckling-induced prolactin release and results in prostatitis in the adult offspring. , 1999, Toxicological sciences : an official journal of the Society of Toxicology.

[4]  Wesley W. Stone,et al.  Update of Watershed Regressions for Pesticides (WARP) for Predicting Atrazine Concentration in Streams , 2009 .

[5]  M. Hedger,et al.  Cytokines and the immune-testicular axis. , 2003, Journal of reproductive immunology.

[6]  J T Stevens,et al.  Chronic effects of atrazine on estrus and mammary tumor formation in female Sprague-Dawley and Fischer 344 rats. , 1994, Journal of toxicology and environmental health.

[7]  I. Huhtaniemi,et al.  Preputial separation as an external sign of pubertal development in the male rat. , 1977, Biology of reproduction.

[8]  W. Battaglin,et al.  The occurrence of glyphosate, atrazine, and other pesticides in vernal pools and adjacent streams in Washington, DC, Maryland, Iowa, and Wyoming, 2005–2006 , 2009, Environmental monitoring and assessment.

[9]  E. Ramsey,et al.  The role of prolactin in the growth of the prostate gland. , 1981, Progress in clinical and biological research.

[10]  W. Scott,et al.  Influence of the pituitary on prostatic response to androgen in the rat. , 1955, Bulletin of the Johns Hopkins Hospital.

[11]  J. Kniewald,et al.  Effects of s-triazine herbicides on hormone-receptor complex formation, 5α-reductase and 3α-hydroxysteroid dehydrogenase activity at the anterior pituitary level , 1979 .

[12]  J. Simpkins,et al.  The mammary tumor response in triazine-treated female rats: A threshold-mediated interaction with strain and species-specific reproductive senescence , 1999, Steroids.

[13]  R. Sharpe,et al.  The critical time window for androgen-dependent development of the Wolffian duct in the rat. , 2007, Endocrinology.

[14]  R. Cooper,et al.  Atrazine disrupts the hypothalamic control of pituitary-ovarian function. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[15]  J. Kniewald,et al.  Effects of s-triazine herbicides on hormone-receptor complex formation, 5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase activity at the anterior pituitary level. , 1979, Journal of steroid biochemistry.

[16]  S. Mccann,et al.  Evidence for a role of prolactin in prostate and seminal vesicle growth in immature male rats. , 1977, Endocrinology.

[17]  L. Gray,et al.  Characterization of the period of sensitivity of fetal male sexual development to vinclozolin. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[18]  C. Wood,et al.  Exposure parameters necessary for delayed puberty and mammary gland development in Long-Evans rats exposed in utero to atrazine. , 2004, Toxicology and applied pharmacology.

[19]  P. Foster,et al.  Critical window of male reproductive tract development in rats following gestational exposure to di-n-butyl phthalate. , 2005, Birth defects research. Part B, Developmental and reproductive toxicology.

[20]  R. Cooper,et al.  Atrazine and reproductive function: mode and mechanism of action studies. , 2007, Birth defects research. Part B, Developmental and reproductive toxicology.

[21]  S. Fenton.  Endocrine-disrupting compounds and mammary gland development: early exposure and later life consequences. , 2006, Endocrinology.

[22]  Keenan Ej,et al.  The role of prolactin in the growth of the prostate gland. , 1981 .

[23]  M. Peruzović,et al.  Indirect influence of s-triazines on rat gonadotropic mechanism at early postnatal period. , 1987, Journal of steroid biochemistry.

[24]  L. Owens,et al.  Atrazine, deethylatrazine, and deisopropylatrazine in surface runoff from conservation tilled watersheds. , 2003, Environmental science & technology.

[25]  R. T. Youker,et al.  Atrazine effects on testosterone levels and androgen-dependent reproductive organs in peripubertal male rats. , 2001, Journal of andrology.

[26]  S. Fenton,et al.  Mammary Gland Development as a Sensitive End Point after Acute Prenatal Exposure to an Atrazine Metabolite Mixture in Female Long-Evans Rats , 2006, Environmental health perspectives.

[27]  V. Papadopoulos,et al.  Gestational exposure to atrazine: effects on the postnatal development of male offspring. , 2008, Journal of andrology.

[28]  R. Cooper,et al.  Effect of atrazine on ovarian function in the rat. , 1996, Reproductive toxicology.

[29]  R. Cooper,et al.  Pubertal development in female Wistar rats following exposure to propazine and atrazine biotransformation by-products, diamino-S-chlorotriazine and hydroxyatrazine. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[30]  R. Cooper,et al.  The effect of atrazine on puberty in male wistar rats: an evaluation in the protocol for the assessment of pubertal development and thyroid function. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[31]  J. Kniewald,et al.  Testosterone metabolism in neuroendocrine organs in male rats under atrazine and deethylatrazine influence. , 1989, Journal of steroid biochemistry.

[32]  R. Cooper,et al.  The effects of atrazine on female wistar rats: an evaluation of the protocol for assessing pubertal development and thyroid function. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[33]  Jennifer Bethsass,et al.  European Union Bans Atrazine, While the United States Negotiates Continued Use , 2006, International journal of occupational and environmental health.

[34]  Thomas Ja,et al.  Effect of prolactin on the metabolism of androgens by the rat ventral prostate gland in vitro. , 1976 .

[35]  P. Foster,et al.  Male Reproductive Tract Lesions at 6, 12, and 18 Months of Age Following in Utero Exposure to Di(n-butyl) Phthalate , 2004, Toxicologic pathology.

[36]  W. Battaglin,et al.  HERBICIDES AND TRANSFORMATION PRODUCTS IN SURFACE WATERS OF THE MIDWESTERN UNITED STATES 1 , 2003 .

[37]  M. Andersen,et al.  Identification of a novel hemoglobin adduct in Sprague Dawley rats exposed to atrazine. , 2006, Chemical research in toxicology.

[38]  P. Foster,et al.  Early-Onset Endocrine Disruptor–Induced Prostatitis in the Rat , 2008, Environmental health perspectives.