Testis and Antler Dysgenesis in Sitka Black-Tailed Deer on Kodiak Island, Alaska: Sequela of Environmental Endocrine Disruption?

It had been observed that many male Sitka black-tailed deer (Odocoileus hemionus sitkensis) on Kodiak Island, Alaska, had abnormal antlers, were cryptorchid, and presented no evidence of hypospadias. We sought to better understand the problem and investigated 171 male deer for phenotypic aberrations and 12 for detailed testicular histopathology. For the low-lying Aliulik Peninsula (AP), 61 of 94 deer were bilateral cryptorchids (BCOs); 70% of these had abnormal antlers. Elsewhere on the Kodiak Archipelago, only 5 of 65 deer were BCOs. All 11 abdominal testes examined had no spermatogenesis but contained abnormalities including carcinoma in situ–like cells, possible precursors of seminoma; Sertoli cell, Leydig cell, and stromal cell tumors; carcinoma and adenoma of rete testis; and microlithiasis or calcifications. Cysts also were evident within the excurrent ducts. Two of 10 scrotal testes contained similar abnormalities, although spermatogenesis was ongoing. We cannot rule out that these abnormalities are linked sequelae of a mutation(s) in a founder animal, followed by transmission over many years and causing high prevalence only on the AP. However, based on lesions observed, we hypothesize that it is more likely that this testis–antler dysgenesis resulted from continuing exposure of pregnant females to an estrogenic environmental agent(s), thereby transforming testicular cells, affecting development of primordial antler pedicles, and blocking transabdominal descent of fetal testes. A browse (e.g., kelp) favored by deer in this locale might carry the putative estrogenic agent(s)

Agricultural Pesticide Use and Hypospadias in Eastern Arkansas

INTRODUCTION: We assessed the relationship between hypospadias and proximity to agricultural pesticide applications using a GIS-based exposure method. METHODS: We obtained information for 354 cases of hypospadias born between 1998 and 2002 in eastern Arkansas; 727 controls were selected from birth certificates. We classified exposure on pounds of pesticides (estimated by crop type) applied or persisting within 500 m of each subject’s home during gestational weeks 6 to 16. We restricted our analyses to 38 pesticides with some evidence of reproductive, developmental, estrogenic, and/or antiandrogenic effects. We estimated timing of pesticide applications using crop phenology and published records. RESULTS: Gestational age at birth [odds ratio (OR) = 0.91; 95% confidence interval (CI), 0.83–0.99], parity (OR = 0.79; 95% CI, 0.65–0.95), and delaying prenatal care until the third trimester (OR = 4.04; 95% CI, 1.46–11.23) were significantly associated with hypospadias. Risk of hypospadias increased by 8% for every 0.05-pound increase in estimated exposure to diclofop-methyl use (OR = 1.08; 95% CI, 1.01–1.15). Pesticide applications in aggregate (OR = 0.82; 95% CI, 0.70–0.96) and applications of alachlor (OR = 0.56; 95% CI, 0.35–0.89) and permethrin (OR = 0.37; 95% CI, 0.16–0.86) were negatively associated with hypospadias. CONCLUSIONS: Except for diclofop-methyl, we did not find evidence that estimated exposure to pesticides known to have reproductive, developmental, or endocrine-disrupting effects increases risk of hypospadias. Further research on the potential effects of exposure to diclofop-methyl is recommended

Concentrations of testosterone (ng/mL) in serum prepared from blood collected shortly after death from NCO and BCO deer

<p><b>Copyright information:</b></p><p>Taken from "Testis and Antler Dysgenesis in Sitka Black-Tailed Deer on Kodiak Island, Alaska: Sequela of Environmental Endocrine Disruption?"</p><p></p><p>Environmental Health Perspectives 2005;114(S-1):51-59.</p><p>Published online 21 Oct 2005</p><p>PMCID:PMC1874179.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI</p> Abbreviations: BCO-NA, BCO deer with normal antlers; BCO-AbA, BCO deer with abnormal antlers without velvet; and BCO-Velv, BCO deer whose antlers retained velvet. Data grouped as NCO-NA, NCO deer with normal antlers. Geometric means were 3.81, 1.73, 2.03, and 0.22 ng/mL, respectively

Kodiak Archipelago, showing the AP of Kodiak Island and numbers of NCO, UCO, and BCO SBTD shot at sites above the dashed line, on the AP and on Sitkinak Island

<p><b>Copyright information:</b></p><p>Taken from "Testis and Antler Dysgenesis in Sitka Black-Tailed Deer on Kodiak Island, Alaska: Sequela of Environmental Endocrine Disruption?"</p><p></p><p>Environmental Health Perspectives 2005;114(S-1):51-59.</p><p>Published online 21 Oct 2005</p><p>PMCID:PMC1874179.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI</p> Note predominance of BCOs on the AP

Timing during ontogeny of the testes, antler pedicles, and limbs in SBTD and postulated actions of an endocrine disruptor to transform testicular cells, alter the antler pedicle primordia, and disrupt transabdominal descent of the testes

<p><b>Copyright information:</b></p><p>Taken from "Testis and Antler Dysgenesis in Sitka Black-Tailed Deer on Kodiak Island, Alaska: Sequela of Environmental Endocrine Disruption?"</p><p></p><p>Environmental Health Perspectives 2005;114(S-1):51-59.</p><p>Published online 21 Oct 2005</p><p>PMCID:PMC1874179.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI</p> Testicular testo: testosterone concentration in total testicular tissue. At “S,” the future scrotum is visible externally as scrotal swellings. Timing of development in SBTD based on data for mule deer () and red deer (; ) scaled to gestation length; duration of gestation assumed as 203 days in SBTD and mule deer and 233 days in red deer. In model animals, transabdominal descent of the testes is blocked by estrogens, whereas passage through the inguinal canal is blocked by antiandrogens (). Insulin-like peptide-3 (Insl3) is involved in transabdominal testicular descent; hence, altered expression of and or a gene could cause cryptorchidism. Products of the fibroblast growth factor gene family (i.e., FGFs) promote early outgrowth of limb buds, with axis patterning controlled by the () gene. genes as well as have been detected in the growth region of regenerating antlers of red deer postnatally (). The primary agent causing abnormalities such as those seen in SBTD, if caused by an endocrine disruptor, might be a phytoestrogen, estrogenic mycotoxin, alkyl phenol, organochlorine, or polychlorinated biphenyl (see text). An antiandrogen might be a co-agent