Plastic Hearts: The Role of Developmental Hypoxia in Turtle Cardiac Resilience

Literature Analysis Assignment for Principles of Animal Physiology (BIO 329L) taught by Dr. Sheila Patek and Dr. Emily Ozdowski at Duke University

September, 2025

Environmental conditions during critical stages of growth can permanently alter physiology, morphology and performance of many bodily systems through a phenomenon known as developmental plasticity. Such plasticity allows a single genotype to produce different phenotypes with varying levels of adaptability in response to stressors during embryonic or fetal development, such as temperature variations, nutrient availability or the presence of toxins or pathogens (Gluckman et al., 2005). 

Hypoxia, a state of insufficient oxygen availability, is a particularly crucial stressor during embryonic development, representing one of the most frequent and severe stresses to an organism’s homeostatic mechanisms (Ducsay et al., 2018). In vertebrates, developmental plasticity in response to oxygen availability shows striking contrasts across lineages. In mammals and birds, exposure to hypoxia during development often leads to maladaptive outcomes, including impaired cardiovascular performance and increased disease risk (Ruhr et al., 2024).  In contrast, recent studies indicate that some ectothermic vertebrates, like turtles, demonstrate remarkable resilience to low oxygen environments, showing adaptive phenotypes that actually enhance survival (Galli et al., 2023). 

Common snapping turtles (Chelydra serpentina) lay their eggs in subterranean nests prone to chronic hypoxia, and juveniles and adults later encounter oxygen limitation during dives or overwintering (Ruhr et al., 2024). This continuity between developmental and ecological stress makes them an excellent model for testing how hypoxia reprograms physiology. Cardiac function depends critically on calcium cycling, a pathway discussed thoroughly during lecture, with the sarcoplasmic reticulum (SR) a key regulator of contraction strength and recovery during stress. Ruhr et al. (2024) built on prior work suggesting that calcium cycling pathways in cardiomyocytes may be permanently altered by developmental hypoxia, hypothesizing that the SR would be reprogrammed to increase calcium sensitivity and improve performance under oxygen deprivation.

To investigate this, the authors raised turtles under normoxia (21% O₂, N21) or hypoxia (10% O₂, H10) and tested isolated cardiomyocytes under normoxia, anoxia, and reoxygenation, with and without pharmacological SR inhibitors. They found that H10 cells had smaller intracellular calcium transients and increased myofilament Ca2+ sensitivity, but normal contraction strength, suggesting that developmental hypoxia may reduce reliance on SR Ca2+ cycling. Under anoxia, H10 cells, but not N21 cells, were able to recover contractions to preanoxic levels, an effect that disappeared when sarcoplasmic reticulum (SR) function was blocked. Their results contribute to growing evidence that chronic developmental hypoxia may rearrange calcium ion pathways of cardiomyocytes to enhance anoxia tolerance. 

A key limitation of this study is that it only compared two developmental oxygen environments: normoxia (21% O₂) and a single hypoxic treatment (10% O₂). In reality, turtle embryos in subterranean nests are likely exposed to a range of oxygen levels that vary with soil composition, microbial activity, and nest depth (Bézy et al., 2014). By testing only the extremes of “normal” and “low” oxygen, the study may oversimplify how developmental hypoxia shapes cardiac physiology. Including multiple intermediate levels of oxygen could reveal whether the observed changes in SR function and calcium sensitivity follow a graded response or whether there are threshold effects.

Additionally, the experiments were performed on isolated cardiomyocytes rather than whole hearts or intact animals. While cell-level measurements provide precise insight into calcium handling and SR function, they cannot capture the integrated responses that occur in a living turtle. While this approach allows precise measurement of calcium transients and contraction, it removes the cells from the complex physiological context of the whole organism. As a result, the findings demonstrate how developmental hypoxia can alter calcium handling at the cellular level, but they may overestimate or underestimate how these changes translate to whole-heart performance. Thus, while this study reveals important mechanisms of SR calcium handling, further work using intact hearts is needed to confirm that these cellular effects translate into whole-organism anoxia tolerance.

AI Assessment Statement 

In preparing this paper, I used Duke’s licensed ChatGPT Edu, to help me condense my draft to the required two-page limit. I asked the tool to take particularly information-heavy sentences that I was struggling to “de-fluff” and simplify them into their essential elements. For example, I prompted it to “what are the scientifically essential elements of this sentence and what can be changed when there is a page limit?” The tool was helpful in breaking down complex ideas into shorter, clearer sentences and in suggesting where content could be combined without losing meaning. The tool was less helpful in producing detailed content restructuring, as it sometimes cut too much nuance, but overall it served as a valuable aid in clarifying and condensing my writing while I remained responsible for the final product.

References

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Bézy, V. S., Valverde, R. A., & Plante, C. J. (2014a). Olive Ridley Sea Turtle Hatching Success as a Function of Microbial Abundance and the Microenvironment of In Situ Nest Sand at Ostional, Costa Rica. Journal of Marine Biology, 2014, 1–10. https://doi.org/10.1155/2014/351921

Ducsay, C. A., Goyal, R., Pearce, W. J., Wilson, S., Hu, X.-Q., & Zhang, L. (2018). Gestational Hypoxia and Developmental Plasticity. Physiological Reviews, 98(3), 1241–1334. https://doi.org/10.1152/physrev.00043.2017

Galli, G. L. J., Lock, M. C., Smith, K. L. M., Giussani, D. A., & Crossley, D. A. (2023). Effects of Developmental Hypoxia on the Vertebrate Cardiovascular System. Physiology (Bethesda, Md.), 38(2), 0. https://doi.org/10.1152/physiol.00022.2022

Gluckman, P. D., Hanson, M. A., Spencer, H. G., & Bateson, P. (2005). Environmental influences during development and their later consequences for health and disease: Implications for the interpretation of empirical studies. Proceedings. Biological Sciences, 272(1564), 671–677. https://doi.org/10.1098/rspb.2004.3001

Isolated Cardiomyocyte—An overview | ScienceDirect Topics. (n.d.). Retrieved September 18, 2025, from https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/isolated-cardiomyocyte

Liu, S. J., & Melchert, R. B. (2010a). In Vitro Cultured Cardiomyocytes for Evaluating Cardiotoxicity. In C. A. McQueen (Ed.), Comprehensive Toxicology (Second Edition) (pp. 113–131). Elsevier. https://doi.org/10.1016/B978-0-08-046884-6.00706-5

Ruhr, I. M., Shiels, H. A., Crossley, D. A., & Galli, G. L. J. (2024). Developmental programming of sarcoplasmic reticulum function improves cardiac anoxia tolerance in turtles. The Journal of Experimental Biology, 227(20), jeb247434. https://doi.org/10.1242/jeb.247434