The Effect of Atrazine Administered by Gavage or in Diet on the LH Surge and Reproductive Performance in Intact Female Sprague‐Dawley and Long Evans Rats

Abstract

Atrazine (ATR) blunts the hormone-induced luteinizing hormone (LH) surge, when administered by gavage (50–100 mg/kg/day for 4 days), in ovariectomized rats. In this study, we determined if comparable doses delivered either by gavage (bolus dose) or distributed in diet would reduce the LH surge and subsequently affect fertility in the intact female rat. ATR was administered daily to intact female Sprague-Dawley (SD) or Long Evans (LE) rats by gavage (0, 0.75 1.5, 3, 6, 10, 12, 50, or 100 mg/kg/day) or diet (0, 30, 100, 160, 500, 660, or 1460 ppm) during one complete 4-day estrous cycle, starting on day of estrus. Estrous status, corpora lutea, ova, and LH plasma concentrations were evaluated. A second cohort of animals was mated on the fourth treatment day. Fertility metrics were assessed on gestational day 20. A higher portion of LE rats had asynchronous estrous cycles when compared to SD rats both during pretreatment and in response to ATR (≥50 mg/kg). In contrast, bolus doses of ATR (≥50 mg/kg) inhibited the peak and area under the curve for the preovulatory LH surge in SD but not LE animals. Likewise, only bolus-treated SD, not LE, rats displayed reduced mean number of corpora lutea and ova. There were no effects of ATR administered by gavage on mating, gravid number, or fetus number. Dietary administration had no effect on any reproductive parameter measured. These findings indicate that short duration, high-bolus doses of ATR can inhibit the LH surge and reduce the number of follicles ovulated; however, dietary administration has no effect on any endocrine or reproductive outcomes

Multigeneration Reproduction and Male Developmental Toxicity Studies on Atrazine in Rats

“…Conversely, reproductive endpoints (LH surge, estrous cycle changes, numbers of corpora lutea, and numbers of collected ova) were not affected by ATR administered in the diet. SD females also showed reductions in the LH surge and the number of ova collected at bolus doses of 50 mg/kg/day and greater, but a significant reduction in the number of corpora lutea was observed only in the 100 mg/kg/day bolus-dosed group (Foradori et al., 2014). These results suggest that effects of ATR or its metabolites on the HPG axis likely occur when their plasma concentrations exceed a critical threshold concentration.…”

“…High doses of ATR administered by gavage have been reported to affect female reproductive processes including impact on the estrous cycle (Cooper et al., 1996), reduction in the luteinizing hormone (LH) surge (Cooper et al., 2000; Simpkins et al., 2011), decreased number of corpora lutea (Foradori et al., 2014), and decreased number of ova shed (Cooper et al., 1996; Foradori et al., 2014). However, these effects were not observed when ATR was administered as a temporally distributed dose in feed (Foradori et al., 2014). Only one study evaluated the multigenerational reproductive effects of 50 ppb ATR administered in drinking water as a mixture with several other pesticides and nitrate (Heindel et al., 1994).…”

Effect of Age, Duration of Exposure, and Dose of Atrazine on Sexual Maturation and the Luteinizing Hormone Surge in the Female Sprague–Dawley Rat

“…The effect of ATZ on fertility and decreased pup survival in Groups 1 and 2 animals administered ATZ at doses of 50 mg/kg/day are consistent with effects observed in other studies where high doses of ATZ were administered by gavage (Foradori et al., 2014; Scialli et al., 2014). Rapid absorption and elimination of ATZ and its chlorometabolites (McMullin et al., 2004) likely account for the absence of effects of ATZ on fertility and pup survival in multigeneration studies, where the daily dose of ATZ (38.7 mg/kg/day) was distributed over the day as determined by infrequent feeding bouts during the day, with most food consumption occurring after lights‐out (DeSesso et al., 2014).…”

“…Oral (gavage) administration of ATZ suppressed the estrogen‐induced (Simpkins et al., 2011) or estrogen‐plus‐progesterone‐induced (McMullin et al., 2004) luteinizing hormone (LH) surge in ovariectomized adult female Sprague–Dawley (SD) (Simpkins et al., 2011), Long Evans (Cooper et al., 2000, 2007), and Wistar (McMullin et al., 2004; Foradori et al., 2009a) rats. ATZ also suppressed the endogenous LH surge that occurs on the afternoon of proestrus in intact, normally cycling female SD rats when administered as a gavage bolus dose of 50 mg/kg/day, but not when administered as a temporally distributed dose in feed (500 ppm) at equivalent daily doses (Foradori et al., 2014). Gavage doses of 50 mg ATZ/day administered to weanling female SD (Ashby et al., 2002) or Wistar rats (Laws et al., 2000) delayed the onset of sexual maturation as indicated by a prolongation in the number of days needed to achieve vaginal patency.…”

Effects of Atrazine on the Development of Neural System of Zebrafish,Danio rerio

“…ATR and its metabolites known as environmental endocrine disruptors (EDCs) have the neuroendocrine toxicity [4]. ATR interferes in endocrine balance by acting on the central nervous system [5–7].…”