Molecular and histological endpoints for developmental reproductive toxicity in Xenopus tropicalis: Levonorgestrel perturbs anti-Mullerian hormone and progesterone receptor expression
2016 (English)In: Comparative Biochemistry and Physiology - Part C: Toxicology & Pharmacology, ISSN 1532-0456, E-ISSN 1878-1659, Vol. 181, 9-18 p.Article in journal (Refereed) PublishedText
There is an increasing concern regarding the risks associated with developmental exposure to endocrine disrupting chemicals and the consequences for reproductive capability. The present study aimed to refine the Xenopus (Silurana) tropicalis test system for developmental reproductive toxicity by characterising molecular and histological features of sexual development, and to explore effects of exposure to the progestagen levonorgestrel (LNG). Larvae were exposed to LNG (0, 3, 30, 300 ng/L) over the first three weeks of development, encompassing the beginning of gonadal differentiation. mRNA levels of amh (anti-Mullerian hormone), amhr2 (amh receptor 2), ipgr (intracellular progesterone receptor), mpgr beta (membrane progesterone receptor beta), and cyp19a1 (cytochrome p450 19a1) were quantified in larvae and juveniles (4 weeks post-metamorphosis). Relative cyp19a1 and amh expression was used as a molecular marker for phenotypic sex of larvae. Gonadal and Mullerian duct development were characterised histologically in juveniles. Compared to controls, LNG exposure increased the expression of amh and ipgr in male larvae. In juveniles, mpgr beta expression was increased in both sexes and amhr2 expression was decreased in males, implying persistent effects of developmental progestagen exposure on amh and pgr expression signalling. No effects of LNG on the gonadal or Mullerian duct development were found, implying that the exposure window was not critical with regard to these endpoints. In juveniles, folliculogenesis had initiated and the Mullerian ducts were larger in females than in males. This new knowledge on sexual development in X. tropicalis is useful in the development of early life-stage endpoints for developmental reproductive toxicity.
Place, publisher, year, edition, pages
2016. Vol. 181, 9-18 p.
Endocrine disruption, Mullerian ducts, Sex differentiation, Test system, Sexual development, Amphibians, Progestagens
IdentifiersURN: urn:nbn:se:uu:diva-282291DOI: 10.1016/j.cbpc.2015.12.001ISI: 000370905700002PubMedID: 26689642OAI: oai:DiVA.org:uu-282291DiVA: diva2:916923
FunderSwedish Research Council Formas, 2011-949-20138-48Carl Tryggers foundation , 12:48Mistra - The Swedish Foundation for Strategic Environmental Research, 2004-147Mistra - The Swedish Foundation for Strategic Environmental Research