Effects of thiourea on the skull of Triturus newts during ontogeny

Abstract

Background In amphibians, thyroid hormone (TH) has a profound role in cranial development, especially in ossification of the late-appearing bones and remodeling of the skull. In the present study, we explored the influence of TH deficiency on bone ossification and resulting skull shape during the ontogeny of Triturus newt hybrid larvae obtained from interspecific crosses between T. ivanbureschi and T. macedonicus. Methods Larvae were treated with two concentrations of thiourea (an endocrine disruptor that chemically inhibits synthesis of TH) during the midlarval and late larval periods. Morphological differences of the cranium were assessed at the end of the midlarval period (ontogenetic stage 62) and the metamorphic stage after treatment during the late larval period. Results There was no difference in the ossification level and shape of the skull between the experimental groups (control and two treatment concentrations) at stage 62. During the late larval period and metamorphosis, TH deficit had a significant impact on the level of bone ossification and skull shape with no differences between the two treatment concentrations of thiourea. The most pronounced differences in bone development were: the palatopterygoid failed to disintegrate into the palatal and pterygoid portions, retardation was observed in development of the maxilla, nasal and prefrontal bones and larval organization of the vomer was retained in thiourea-treated larvae. Conclusions This implies that deficiency of TH caused retardation in development and arrested metamorphic cranium skeletal reorganization, which resulted in divergent cranial shape compared to the control group. Our results confirmed that skull remodeling and ossification of late-appearing bones is TH–dependent, as in other studied Urodela species. Also, our results indicate that TH plays an important role in the establishment of skull shape during the ontogeny of Triturus newts, especially during the late larval period and metamorphosis, when TH concentrations reach their maximum.

Changes in thyroid histomorphology and thyroglobulin immunostaining upon exposure to thiourea in Triturus newts

“…Larvae treated with thiourea have "arrested metamorphosis", which means they did not metamorphose but continue to growth while retaining larval characteristics (larval cranial morphology with well-developed gills, larval thin skin and pigmentation). Also, results are in agreement with thiourea effects on cranial morphology obtained from the same Triturus larvae used in this study (Ajduković et al, 2021) and from independent set of Triturus larvae used for oxidative stress status (Gavrić et al, 2021). The deficit in the THs level in the blood in thiourea-treated larvae slowed down cranial remodeling during metamorphosis and they retained late larval cranial morphology (Ajduković et al, 2021).…”

“…The mechanism of action is very similar for all anti-thyroid agents via inhibition of the thyroid peroxidase enzyme, thereby inhibiting iodination of tyrosine residues in thyroglobulin, the oxidative coupling of iodinated tyrosine, and therefore the biosynthesis of the thyroid hormones (Davidson et al, 1979). Thiourea exposure was reported to inhibit metamorphosis in anuran tadpoles (Steinmetz, 1950;Krishnapriya et al, 2014) and cause a delay in cranial osteology of newly metamorphosed newts (Smirnov and Vassilieva, 2003a, 2003bSmirnov et al, 2011;Ajduković et al, 2021). In nature, thiourea may be present in surface waters and sediments over prolonged periods (Mutic et al, 2017) because it is added to fertilizers to inhibit the nitrification process (Wang et al, 2017) and thiourea could thus directly threaten amphibians in their natural habitat.…”

Targeting Thyroid Hormone/Thyroid Hormone Receptor Axis: An Attractive Therapy Strategy in Liver Diseases

“…Dysfunction of the TH/TR axis leads to numerous pathologies, especially including growth, skeletal development, heart diseases, cognitive dissonance, gastrointestinal function, obesity, dysmetabolism, and cancers ( Brent, 2012 ; Ortiga-Carvalho et al, 2014 ; Ajdukovic et al, 2021 ; Moutzouri et al, 2021 ; Niedowicz et al, 2021 ; Salman et al, 2021 ). Therefore, the abnormity of the TH/TR axis elicits a series of diseases, the most common of which is metabolic disease ( Malm, 2004 ).…”

Increasing Hormonal Control of Skeletal Development: An Evolutionary Trend in Amphibians

“…Thus, dysfunction of the thyroid axis was revealed to account for the absence of several bones in neotenic salamanders retaining larval cranial morphology as an adult morphology (Larsen, 1968;Rosenkilde and Ussing, 1996;Rose, 2003). Thyroid axis involvement in the cranial development of plethodontids and salamandrids was estimated in a series of experiments with exogenous TH and goitrogen treatment of larvae developing in a regime of high and low TH levels or hypophysectomized larvae (Rose, 1995a(Rose, ,b, 1996Clemen and Greven, 2018;Ajduković et al, 2021).…”