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Functional and regulatory aspects of oxidative stress response in X monosomy

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Abstract

The partial/complete loss of one X chromosome in a human female leads to Turner syndrome (TS). TS individuals display a range of phenotypes including short stature, osteoporosis, ovarian malfunction, diabetes, and thyroid dysfunction. Epigenetic factors and regulatory networks are distinctly different in X monosomy (45, X). In a lifetime, an individual is exposed to a variety of stress conditions. To study whether X monosomy cells display a differential response upon exposure to mild stress as compared to normal 46, XX cells and whether this may contribute to various co-morbidities in aneuploid individuals, we have carried out a transcriptomic analysis of human fibroblasts 45, X and 46, XX after exposure to mild oxidative stress. Under these conditions, over 350 transcripts were seen to be differentially expressed in 45, X and 46, XX cells. Pathways associated with oxidative stress were differentially expressed highlighting the differential regulation of genes and associated phenotypes. It could be seen that X monosomy cells are more susceptible to oxidative stress as compared to normal cells and have altered molecular pathways both in normal conditions and also upon exposure to mild oxidative stress. To explore this aspect in detail, we have mapped the expressions of transcription factors (TFs) in 45, X and 46, XX cells. The network of transcription activating factors is differentially regulated in 45, X and 46, XX cells under stress exposure. It is tempting to speculate that the altered ability of 45, X (Turner) cells to respond to stress may play a significant role in the physiological function and altered phenotypes in Turner syndrome.

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Acknowledgements

The authors thank Prof. Dileep N. Deobagkar, Dr. Mandar Paingankar, and Dr. Santosh Narwade for valuable suggestions. DDD and VB thank MoES, GOI, and ISRO for financial support.

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  1. Molecular Biology Research Laboratory, Department of Zoology, Savitribai Phule Pune University, Pune, India

    Vinayak S. Biradar, Shriram N. Rajpathak, Suraj R. Joshi & Deepti D. Deobagkar

  2. Recombinant Department, Serum Institute of India Pvt. Ltd., Pune, 411 028, India

    Shriram N. Rajpathak

  3. School of Physical Sciences, ISRO Space Technology Cell, Savitribai Phule Pune University, Pune, 411 007, India

    Deepti D. Deobagkar

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  1. Vinayak S. Biradar
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Correspondence to Deepti D. Deobagkar.

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Biradar, .S., Rajpathak, S.N., Joshi, S.R. et al. Functional and regulatory aspects of oxidative stress response in X monosomy. In Vitro Cell.Dev.Biol.-Animal 57, 661–675 (2021). https://doi.org/10.1007/s11626-021-00604-3

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