Parikh Rasesh Y, Gangaraju Vamsi K
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA.
Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
Environ Epigenet. 2022 Dec 28;9(1):dvac030. doi: 10.1093/eep/dvac030. eCollection 2023.
Developmental robustness represents the ability of an organism to resist phenotypic variations despite environmental insults and inherent genetic variations. Derailment of developmental robustness leads to phenotypic variations that can get fixed in a population for many generations. Environmental pollution is a significant worldwide problem with detrimental consequences of human development. Understanding the genetic basis for how pollutants affect human development is critical for developing interventional therapies. Here, we report that environmental stress induced by hexavalent chromium, Cr(VI), a potent industrial pollutant, compromises developmental robustness, leading to phenotypic variations in the progeny. These phenotypic variations arise due to epigenetic instability and transposon activation in the somatic tissues of the progeny rather than novel genetic mutations and can be reduced by increasing the dosage of Piwi - a Piwi-interacting RNA-binding protein, in the ovary of the exposed mother. Significantly, the derailment of developmental robustness by Cr(VI) exposure leads to tumors in the progeny, and the predisposition to develop tumors is fixed in the population for at least three generations. Thus, we show for the first time that environmental pollution can derail developmental robustness and predispose the progeny of the exposed population to develop phenotypic variations and tumors.
发育稳健性是指生物体尽管受到环境侵害和内在遗传变异的影响，但仍能抵抗表型变异的能力。发育稳健性的偏离会导致表型变异，这些变异可能会在一个种群中固定许多代。环境污染是一个重大的全球性问题，对人类发展产生有害影响。了解污染物如何影响人类发育的遗传基础对于开发干预疗法至关重要。在此，我们报告称，由强效工业污染物六价铬（Cr(VI)）引起的环境应激会损害发育稳健性，导致后代出现表型变异。这些表型变异是由于后代体细胞组织中的表观遗传不稳定性和转座子激活引起的，而不是新的基因突变，并且可以通过增加暴露母体卵巢中Piwi（一种与Piwi相互作用的RNA结合蛋白）的剂量来减少。值得注意的是，Cr(VI)暴露导致的发育稳健性偏离会导致后代出现肿瘤，并且患肿瘤的易感性在种群中至少三代都保持不变。因此，我们首次表明，环境污染会破坏发育稳健性，并使暴露人群的后代易出现表型变异和肿瘤。
