Hypoxia turns genotypic female medaka fish into phenotypic males
Hypoxia caused by eutrophication is amongst the most pressing global problems in aquatic systems. Notably, more than 400 “dead zones” have been identified worldwide, resulting in large scale collapse of fisheries and major changes in the structure and trophodynamics. Recent studies further discovered that hypoxia can also disrupt sex hormone metabolism and alter the sexual differentiation of fish, resulting in male biased F1 generations and therefore posing a threat to the sustainability of natural populations. However, it is not known whether, and if so how, hypoxia can also change the sex ratio in vertebrates that have sex-determining XX/XY chromosomes. Using the Japanese medaka (Oryzias latipes) as a model, we demonstrate, for the first time, that hypoxia can turn genotypic female fish with XX chromosomes into phenotypic males. Over half of the XX females exposed to hypoxia exhibit male secondary sexual characteristics and develop testis instead of ovary. We further revealed that hypoxia can: (a) down-regulate the vasa gene, which controls proliferation of primordial germ cells and gonadal sex differentiation into ovary, and (b) up-regulate the DMY gene which resides at the sex-determining locus of the Y chromosome, and direct testis differentiation. This is the first report that hypoxia can directly act on genes that regulate sex determination and differentiation, thereby turning genotypic females into phenotypic males and leading to a male-dominant F1 population.
KeywordsHypoxia Sex determination DMY vasa Male biased F1 generation
The work described in this paper was supported by a Grant from the University Grants Committee of the Hong Kong Special Administrative Region, China (AoE/P-04/04) and a postgraduate student granted to Catis Cheung by the City University of Hong Kong.
Conflict of interest
The authors declare that they have no conflict of interest.
- Blázquez M, González A, Mylonas CC, Piferrer F (2011) Cloning and sequence analysis of a vasa homolog in the European sea bass (Dicentrarchus labrax): tissue distribution and mRNA expression levels during early development and sex differentiation. Gen Comp Endocrinol 170:322–333CrossRefGoogle Scholar
- Boswell MG, Wells MC, Kirk LM, Ju Z, Zhang Z, Booth RE, Walter RB (2009) Comparison of gene expression responses to hypoxia in viviparous (Xiphophorus) and oviparous (Oryzias) fishes using a medaka microarray. Comp Biochem Physiol C 149:258–265Google Scholar
- Diaz RJ, Rosenberg R (2011) Introduction to environmental and economic consequences of hypoxia. Int J Water Resour D 27:71–82Google Scholar
- Jewell UR, Kvietikova I, Scheid A, Bauer C, Wenger RH, Gassmann M (2001) Induction of HIF-1α in response to hypoxia is instantaneous. FASEB J 15:1312–1314Google Scholar
- Keckeis H, Bauer-Nemeschkal E, Kamler E (1996) Effects of reduced oxygen level on the mortality and hatching rate of Chondrostoma nasus embryos. J Fish Biol 49:430–440Google Scholar
- Oehlers LP, Perez AN, Walter RB (2007) Detection of hypoxia-related proteins in medaka (Oryzias latipes) brain tissue by difference gel electrophoresis and de novo sequencing of 4-sulfophenyl isothiocyanate-derivatized peptides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Comp Biochem Physiol C 145:120–133Google Scholar
- Pincetich CA, Viant MR, Hinton DE, Tjeerdema RS (2005) Metabolic changes in Japanese medaka (Oryzias latipes) during embryogenesis and hypoxia as determined by in vivo 31P NMR. Comp Biochem Physiol C 140:103–113Google Scholar
- Satoh N, Egami N (1972) Sex differentiation of germ cells in the teleost, Oryzias latipes, during normal embryonic development. J Embryol Exp Morphol 28:385–395Google Scholar
- STAP (2011) Hypoxia and nutrient reduction in the coastal zone: advice for prevention, remediation and research. A STAP Advisory Document. Global Environment Facility, Washington, DCGoogle Scholar
- Taglialatela R, Della Corte F (1997) Human and recombinant erythropoietin stimulate erythropoiesis in the goldfish Carassius auratus. Eur J Histochem 41:301–304Google Scholar
- Wu RSS (2009) Chapter 3 effects of hypoxia on fish reproduction and development. In: Richards JG, Farrell AP, Brauner CJ (eds) Fish physiology, vol 27. Academic Press, Amsterdam, pp 79–141Google Scholar
- Yu R, Chen E, Kong R, Ng P, Mok H, Au D (2006) Hypoxia induces telomerase reverse transcriptase (TERT) gene expression in non-tumor fish tissues in vivo: the marine medaka (Oryzias melastigma) model. BMC Mol Biol 7:1–12Google Scholar
- Zar JH (1999) Biostatistical analysis, 4th edn. Prentice Hall, Englewood CliffsGoogle Scholar
- Zhang Z, Wells MC, Boswell MG, Beldorth I, Kirk LM, Wang Y, Wang S, Savage M, Walter RB, Booth RE (2012) Identification of robust hypoxia biomarker candidates from fin of medaka (Oryzias latipes). Comp Biochem Physiol C 155:11–17Google Scholar