17β‐Estradiol Exposure Accelerates Skeletal Development in Xenopus laevis Tadpoles

Abstract

Although it is well established that estrogen regulates skeletal growth and ossification in mammals, the effects of estrogen on skeletal development in amphibians are relatively uncharacterized. This study was conducted to characterize the impact of 17b-estradiol exposure on skeletal development in Xenopus laevis tadpoles. On day 48 postfertilization, tadpoles were placed in tanks containing 50% Holtfreter's Solution AE17b-estradiol at one of four concentrations (10 À11 , 10 À10 , 10 À9 , and 10 À8 M). At 7-11 day intervals until day 91, 7-10 tadpoles per group were killed, fixed, measured, and staged. Specimens were then cleared and double-stained for cartilage and bone, and 34 skeletal elements were analyzed for ossification. Results from the study indicate that both low (10 À11 M) and high (10 À8 M) concentrations of 17b-estradiol have a significant stimulatory effect on tadpole development. Both the larval stage and ossification index of tadpoles exposed to 10 À11 or 10 À8 M 17b-estradiol were significantly greater than those observed in control animals by day 91 postfertilization. These results are consistent with the hypothesis that endogenous and exogenous estrogen could play a role in the regulation of bone ossification in amphibians. Anat Rec, 293:1880Rec, 293: -1886Rec, 293: , 2010. V V C 2010 Wiley-Liss, Inc.Key words: estradiol; skeleton; bone; Xenopus laevis; metamorphosis; ossification; development Numerous studies have demonstrated that the female sex hormone estrogen has profound effects on the development and maintenance of the mammalian skeleton. These effects include the induction of sexually dimorphic characteristics through actions exerted during the prenatal, postnatal, and pubertal periods (reviewed in Turner et al., 1994); regulation of linear skeletal growth in both sexes, especially during puberty (reviewed in Nilsson et al., 2005); and reduction in the rate of bone remodeling and thus protection against bone loss after sexual maturation (reviewed in Manolagas et al., 2002).Perhaps the most significant of the skeletal effects of estrogen during development are its actions on longitudinal bone growth. In mammals as well as in other vertebrates, longitudinal bone growth occurs through a process known as endochondral ossification, during which chondrogenesis (cartilage formation), followed by remodeling of cartilage into bone (ossification), takes place in the growth plates at the ends of long bones (Nilsson et al., 2005). Mammalian studies investigating the influence of estrogen on this process have demonstrated that the sex steroid can have profound stimulatory and/or inhibitory effects on endochondral ossification in both males and females, depending on the species, dose, and developmental stage of exposure.

Environmentally-relevant concentrations of atrazine induce non-monotonic acceleration of developmental rate and increased size at metamorphosis in Rhinella arenarum tadpoles

“…Interestingly, tadpoles exposed to 17b-estradiol presented the exact same alterations of developmental rate and body size as those treated with 1, 10 and 100 mg/L of atrazine. Similar accelerations of metamorphosis in response to estradiol have previously been demonstrated by Coady et al (2004) and Bauer-Dantoin and Meinhardt (2010), but inhibitions of developmental rate were also observed in other studies (Gray and Janssens, 1990;Hogan et al, 2008;Kloas et al, 2009;Sharma and Patin ˜o, 2010). Although the current study was not designed to examine potential mechanisms by which atrazine might influence metamorphosis, general hypotheses can be proposed regarding potential modes of action.…”

“…A mode of action involving a steroid hormone receptor would be coherent with the non-monotonic concentration-response curves observed in the current study as non-monotonic curves are characteristic of physiological responses to estradiol and other hormones acting through steroid hormone receptors (Calabrese et al, 2007;Bauer-Dantoin and Meinhardt, 2010;Peterson Myers et al, 2009). Although the mechanisms underlying these nonmonotonic concentration-response behaviors are not yet fully understood, they are possibly due to the inherently nonlinear process of receptor homodimerization implicated in steroid hormone receptor signaling (Li et al, 2007).…”

Sodium perchlorate disrupts development and affects metamorphosis- and growth-related gene expression in tadpoles of the wood frog (Lithobates sylvaticus)

“…However, several studies in amphibians and fish have also documented the effects of these estrogens on both development and growth. For example, early development or embryonic exposure to E 2 accelerated the development and increased growth as assessed by body weight and/or length in X. laevis at concentrations of 1 lM (Nishimura et al, 1997) or 0.01 nM (Bauer-Dantoin and Meinhardt, 2010). Delayed metamorphosis was also reported in E 2 -treated X. laevis males (Sharma and Patiño, 2010) and EE 2 -treated X. laevis (Tompsett et al, 2012;Pettersson and Berg, 2006).…”

“…The effects on amphibian larval growth and/or development have been reported in a growing number of studies as an unintended and sometimes unexpected effect of endocrine disruptors that have been used primarily to disrupt either the thyroid or the sexual differentiation endocrine axis (Bauer-Dantoin and Meinhardt, 2010;Goleman et al, 2002a;Tompsett et al, 2012;Nishimura et al, 1997;Hogan et al, 2006Hogan et al, , 2008, however the nature of any interactions are at present unclear. This study aims to specifically examine the effect of endocrine disruptors on the growth and development of wood frog (Lithobates sylvaticus) tadpoles, a native North American species.…”