Exposure to 9-cis retinoic acid induces penis and vas deferens development in the female rock shell, Thais clavigera

Abstract

To clarify how tributyltin (TBT) and triphenyltin (TPT) interact with the retinoid X receptor (RXR) to induce growth of male sex organs in female gastropods, we treated female rock shells (Thais clavigera) with three different concentrations (0.1, 1, or 5 microg/g wet wt) of 9-cis-retinoic acid (9CRA) or with a single concentration (1 microg/g wet wt) of TBT, TPT, or fetal bovine serum (as a control). The effects of each treatment were measured as the incidence of imposex, the length of the penis-like structure, and the vas deferens sequence (VDS) index. 9CRA induced imposex in a dose-dependent manner; imposex incidence was significantly higher in the rock shells that received 1 (P < 0.05) or 5 microg (P < 0.001) 9CRA than in the controls. After 1 month, the rock shells treated with 5 microg 9CRA exhibited substantial growth of the penis-like structure that was not as evident in the other treated shells. The length of the structure differed between the 0.1- and 5-microg 9CRA treatment groups (P < 0.05) but not between the 1- and 5-microg 9CRA treatment groups (P > 0.05). Compared with the control, the VDS index increased significantly in the 1- (P < 0.05) and 5-microg (P < 0.001) 9CRA groups. The penis-like structures behind the right tentacle in female rock shells treated with 5 microg 9CRA were essentially the same as the penises and vasa deferentia of normal males and of TBT-treated or TPT-treated imposexed females. These results further support the hypothesis that imposex in gastropods could be mediated by RXR.

Birth Defects in Wildlife: The Role of Environmental Contaminants as Inducers of Reproductive and Developmental Dysfunction

“…Cloning of the RXR homologue from the gastropod rock shell (Thais clavigera) reveals that the ligand-binding domain of rock shell RXR is very similar to human RXR and also binds strongly to TBT [Nishikawa et al 2004;Nishikawa 2006]. It was discovered that activation of RXR through injections of RA into female rock shells induces imposex [Horiguchi et al 2008]. These results suggest that RXR plays a critical role in the development of imposex and is important in the induction, differentiation, and growth of male reproductive organs in female gastropods.…”

Endocrine disruption and altered sexual development in aquatic organisms: an invertebrate perspective

“…Although oestrogenic effects predominate the ED literature on fish, a small number of masculinization events have been reported in several FW species (mosquitofish, killifish and catfish) in conjunction with exposure to pulp mill effluent (possibly due to androstenedione from bacterial degradation of plant sterols) and also from inputs of androgenic anabolic steroids from intensive cattle farming (Howell, 1999). Downstream, estuarine and coastal fauna could be vulnerable to these and other androgenic EDC (Alvarez-Munoz et al ., 2015), given that the androgen receptor (AR) in some marine species is known to bind contaminants such as organochlorines, albeit weakly, which may subsequently impair the gamete-maturation signalling pathway (Oberdorster & Cheek, 2001).…”

Establishment of a polyclonal antibody against the retinoid X receptor of the rock shell Thais clavigera and its application to rock shell tissues for imposex research

“…However, the scientific debate continues on the mechanisms by which organotins induce imposex in gastropods because, as noted by Horiguchi et al (2008) and Horiguchi (2009), each of these hypotheses is insufficient to explain the phenomenon. Nishikawa et al (2004) found that T. clavigera has a retinoid X receptor (RXR) that is similar to those in humans and other vertebrates as well as to those in other invertebrates, such as ascidians, insects, pulmonates, jellyfish, and sponges (Bouton et al 2005;Devine et al 2002;Freebern et al 1999;Heyman et al 1992;Kamimura et al 2000;Kostrouch et al 1998;Mangelsdorf and Evans 1995;Mangelsdorf et al 1992;Wiens et al 2003).…”