title: Environmental-endocrine control of reproductive maturation in gastropods: implications for the mechanism of tributyltin-induced imposex in prosobranchs.
abstract: Prosobranch snails have been afflicted globally by a condition whereby females develop male sex characteristics, most notably a penis. This condition, known as imposex, has been causally associated with the ubiquitous environmental contaminant tributyltin (TBT). Deduction of the mechanism by which TBT causes imposex has been hampered by the lack of understanding of the normal endocrine regulation of reproductive tract recrudescence in these organisms. We have reviewed the relevant literature on the environmental and endocrine factors that regulate reproductive tract recrudescence, sexual differentiation, and reproduction in gastropods. We provide a cohesive model for the environmental-endocrine regulation of reproduction in these organisms, and use this information to deduce a most likely mechanism by which TBT causes imposex. Photoperiod appears to be the predominant environmental cue that regulates reproductive tract recrudescence. Secondary cues include temperature and nutrition which control the timing of breeding and egg laying. Several hormone products of the central and peripheral nervous systems have been identified that contribute to recrudescence, reproductive behaviors, oocyte maturation and egg laying. Retinoic acid signaling via the retinoid X-receptor (RXR) has shown promise to be a major regulator of reproductive tract recrudescence. Furthermore, TBT has been shown to be a high affinity ligand for the RXR and the RXR ligand 9-cis retinoic acid causes imposex. We propose that TBT causes imposex through the inappropriate activation of this signaling pathway. However, uncertainties remain in our understanding of the environmental-endocrine regulation of reproduction in gastropods. Definitive elucidation of the mechanism of action of TBT awaits resolution of these uncertainties.
authors: Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, NC 27695, USA.
authors: Robin M
authors: RM
authors: Sternberg
authors: Meredith P
authors: MP
authors: Gooding
authors: Andrew K
authors: AK
authors: Hotchkiss
authors: Gerald A
authors: GA
authors: LeBlanc
mesh_terms: D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D005260:Female; D008297:Male; D008954:Models, Biological; D017440:Photoperiod; D047488:Retinoid X Receptors / Q000378:metabolism; D012727:Sex Characteristics; D012733:Sex Differentiation / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D012908:Snails / Q000187:drug effects / Q000502:physiology*; D013696:Temperature; D014212:Tretinoin / Q000378:metabolism; D014220:Trialkyltin Compounds / Q000378:metabolism / Q000633:toxicity*
chemical_list: D047488:Retinoid X Receptors; D014220:Trialkyltin Compounds; C011559:tributyltin; D014212:Tretinoin