4208 INTRODUCTION Many freshwater aquatic vertebrates may be subjected to hypoxic stress at more frequent and variable schedules than marine or terrestrial species (Nikinmaa, 2002; Pelster, 2002; Farrell, 2007; Tattersall and Ultsch, 2008; Porteus et al., 2011; Richards, 2011; Sandblom and Axelsson, 2011). In addition to the immediate cardio- respiratory physiological responses, which have been well characterized, freshwater fish can develop acclimatory phenotypes in response to hypoxic conditions, presumably affording greater hypoxic resistance during that hypoxic episode and perhaps any subsequent hypoxia challenge (Pelster, 2002; Richards, 2011). For example, many species show branchial remodeling, including hypertrophy, in response to aquatic hypoxia (see Jonz et al., 2004; Negreiros et al., 2011; Tzaneva et al., 2011). Such changes in gill structure are typically viewed as a beneficial acclimation response. In addition to physiological and morphological responses to environmental stressors that affect their own survival, adult fishes respond in ways that may influence the survival of their offspring in such environments. Such changes can include alterations of the egg environment through inclusion of hormonal and other signals in the yolk (e.g. Lindeman and Pelegri, 2010; Segers et al., 2012). Such changes constitute a so-called ‘maternal’ or ‘parental’ effect (sometimes referred to as a ‘indirect genetic effect’ or even ‘transgenerational plasticity’). Not all of these effects are beneficial. Hypoxic exposure in adult freshwater fish can reduce fitness due to low fecundity, decreased mating rates and low survivorship of offspring (Wu et al., 2003). When exposed to even moderate levels of hypoxia, adult carp, for example, suffer disruption of the endocrine system that lowers offspring hatchability as well as induces lethal mutation phenotypes in offspring (Wu et al., 2003). In contrast, resistance to a stressor may be conferred upon the offspring. For example, killifish and feral white suckerfish from recently polluted environments produce offspring that are more resistant to the specific pollutant (Munkittrick and Dixon, 1988; Meyer et al., 2003), likely through parental influences on the egg environment in which early development occurs. Collectively, then, there is evidence among fishes indicating a link between the stressors experienced by the parents and the increased fitness of their offspring to survive these same stressors. While such enhanced offspring fitness in the past has often been interpreted in the traditional context of heritable changes in gene sequence leading to altered phenotype across generations, there has been a burgeoning of epigenetic studies of stressors in environments and how they are specifically affecting transgenerational transfer of phenotype without alteration in gene sequence [for discussion, see Lacey (Lacey, 1998) and Ho and Burggren (Ho and Burggren, 2010)]. Most studies of transgenerational epigenetics in fishes as they relate to enhanced offspring resistance have focused on environmental contaminants (e.g. heavy metals and other toxicants). SUMMARY Parental influences are a potentially important component of transgenerational transfer of phenotype in vertebrates. This study examined how chronic hypoxic exposure on adult zebrafish (Danio rerio) affected the phenotype of their offspring. Separate adult populations were exposed to hypoxia (13.1 kPa O 2 ) or normoxia (21.1 kPa O 2 ) for periods ranging from 1 to 12 weeks. Adults were then returned to normoxia and bred within experimental groups. Adult fecundity and egg characteristics (volume of egg, yolk and perivitelline fluid) were assessed. Subsequently, larval body length, time to loss of equilibrium in severe hypoxia (~4 kPa O 2 ), and critical thermal minima (CT min ) and maxima (CT max ) were measured at 6, 9, 12, 15, 18, 21 and 60 days post-fertilization (d.p.f.). Adult fecundity was depressed by hypoxic exposure. Egg component volumes were also depressed in adults exposed to 1–2 weeks of hypoxia, but returned to control levels following longer hypoxic exposure. Adult hypoxic exposures of >1 week resulted in longer body lengths in their larval offspring. Time to loss of equilibrium in severe hypoxia (i.e. hypoxic resistance) in control larvae decreased from 6 to 12 d.p.f., remaining constant thereafter. Notably, hypoxic resistance from 6 to 18 d.p.f. was ~15% lower in larvae whose parents were exposed to just 1 week of chronic hypoxia, but resistance was significantly increased by ~24–30% in 6–18 d.p.f. larvae from adults exposed to 2, 3 or 4 weeks of hypoxia. CT min (~10–12°C) and CT max (~39.5°C) were unchanged by parental hypoxic exposure. This study demonstrates that parental hypoxic exposure in adult zebrafish has profound epigenetic effects on the morphological and physiological phenotype of their offspring. Key words: parental effect, critical thermal maxima, epigenetics. Received 8 May 2012; Accepted 13 August 2012 The Journal of Experimental Biology 215, 4208-4216 © 2012. Published by The Company of Biologists Ltd doi:10.1242/jeb.074781 RESEARCH ARTICLE Parental hypoxic exposure confers offspring hypoxia resistance in zebrafish (Danio rerio) Dao H. Ho 1,2 and Warren W. Burggren 1, * 1 Developmental Integrative Biology Research Cluster, Department of Biological Sciences, University of North Texas, 1155 Union Circle #305220, Denton, TX 76203-5017, USA and 2 Section of Experimental Medicine, Department of Medicine, Georgia Health Sciences University, 1459 Laney Walker Boulevard, CB 2200, Augusta, GA 30912, USA *Author for correspondence (burggren@unt.edu) THE฀JOURNAL฀OF฀EXPERIMENTAL฀BIOLOGY