Demasculinization and feminization of male gonads by atrazine: Consistent effects across vertebrate classes

Abstract

Atrazine is the most commonly detected pesticide contaminant of ground water, surface water, and precipitation. Atrazine is also an endocrine disruptor that, among other effects, alters male reproductive tissues when animals are exposed during development. Here, we apply the nine so-called “Hill criteria” (Strength, Consistency, Specificity, Temporality, Biological Gradient, Plausibility, Coherence, Experiment, and Analogy) for establishing cause–effect relationships to examine the evidence for atrazine as an endocrine disruptor that demasculinizes and feminizes the gonads of male vertebrates. We present experimental evidence that the effects of atrazine on male development are consistent across all vertebrate classes examined and we present a state of the art summary of the mechanisms by which atrazine acts as an endocrine disruptor to produce these effects. Atrazine demasculinizes male gonads producing testicular lesions associated with reduced germ cell numbers in teleost fish, amphibians, reptiles, and mammals, and induces partial and/or complete feminization in fish, amphibians, and reptiles. These effects are strong (statistically significant), consistent across vertebrate classes, and specific. Reductions in androgen levels and the induction of estrogen synthesis – demonstrated in fish, amphibians, reptiles, and mammals – represent plausible and coherent mechanisms that explain these effects. Biological gradients are observed in several of the cited studies, although threshold doses and patterns vary among species. Given that the effects on the male gonads described in all of these experimental studies occurred only after atrazine exposure, temporality is also met here. Thus the case for atrazine as an endocrine disruptor that demasculinizes and feminizes male vertebrates meets all nine of the “Hill criteria”.

Atrazine disrupts gonadal development in a live-bearing lizard

“…68,69 Furthermore, testicular lesions following ATZ exposure have been observed in reproductively mature Carassius auratus 70 and laboratory rodents. 68,69 Despite differences in life stages and class of the experimental subjects, ATZ appears to have consistent effects on the testes of vertebrates; 22 our results extend these findings to viviparous reptiles.…”

“…Rather, we suggest that testicular lesions may reflect decreased availability of dihydrotestosterone (DHT). Atrazine decreases androgen synthesis via multiple pathways (reviewed in Hayes et al 22 ). Atrazine inhibits 5a reductase activity, 72 which reduces dihydrotestosterone (DHT) synthesis, 22 and inhibits DHT binding to binding proteins and receptors in vitro, 23 thus reducing DHT synthesis and potency.…”

“…This EDC increases expression of the enzyme aromatase [14][15][16][17] which converts aromatisable androgens to estrogens. 18 Atrazine also decreases circulating HPG hormones including gonadotrophin releasing hormone (GnRH), luteinizing hormone (LH) [19][20][21] and the androgen dihydrotestosterone (DHT), 22 and alters DHT availability. 23 Consistent effects of ATZ have been identified in representatives of all the major vertebrate groups, 22 but the only viviparous vertebrates in which the effects of ATZ have been studied are laboratory rodents.…”

“…18 Atrazine also decreases circulating HPG hormones including gonadotrophin releasing hormone (GnRH), luteinizing hormone (LH) [19][20][21] and the androgen dihydrotestosterone (DHT), 22 and alters DHT availability. 23 Consistent effects of ATZ have been identified in representatives of all the major vertebrate groups, 22 but the only viviparous vertebrates in which the effects of ATZ have been studied are laboratory rodents. Although laboratory rodents may be useful models for assessment of the effects of some EDCs, 3,9 they are not the most appropriate with which to study the effects of ATZ in viviparous vertebrates.…”

Effects of Post-Weaning Consumption of Soy Isoflavones on Prepubertal and Postpubertal Serum Levels of Some Reproductive Hormones of Male Wistar Rats

“…Testosterone works with estrogen to regulate reproductive behaviors that lead to copulation [30]. Once released by the testes, testosterone is converted by the aromatase enzyme into estradiol, which then acts similarly in its effects on male behavior [31].…”