Rapid and Efficient Spatiotemporal Monitoring of Normal and Aberrant Cytosine Methylation within Intact Zebrafish Embryos

Avila-Barnard, Sarah; Volz, David C.

doi:10.3791/64190

Cited by 1 publication

(1 citation statement)

References 18 publications

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“…Methylation happens at the fifth carbon position of a cytosine residue to form 5-methyl cytosine (5mC). Demethylation also occurs to form 5-hydroxy-methyl cytosine (5hmC), a product of 5mC demethylation catalysed by the Ten-Eleven Translocation (TET) protein family [ 1 , 2 ]. Demethylation has been reported to control many cellular and developmental processes, including the pluripotency of embryonic stem cells, differentiation and neuron development, and tumorigenesis in mammals, for example [ 3 , 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

A Paternal Methylation Error in the Congenital Hydrocephalic Texas (H-Tx) Rat Is Partially Rescued with Natural Folate Supplements

Naz

Moshkdanian

Miyan

et al. 2023

IJMS

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Folate deficiencies, folate imbalance and associated abnormal methylation are associated with birth defects, developmental delays, neurological conditions and diseases. In the hydrocephalic Texas (H-Tx) rat, 10-formyl tetrahydrofolate dehydrogenase (FDH) is reduced or absent from the CSF and the nuclei of cells in the brain and liver and this is correlated with decreased DNA methylation. In the present study, we tested whether impaired folate metabolism or methylation exists in sexually mature, unaffected H-Tx rats, which may explain the propagation of hydrocephalus in their offspring. We compared normal Sprague Dawley (SD, n = 6) rats with untreated H-Tx (uH-Tx, n = 6 and folate-treated H-Tx (TrH-Tx, n = 4). Structural abnormalities were observed in the testis of uH-Tx rats, with decreased methylation, increased demethylation, and cell death, particularly of sperm. FDH and FRα protein expression was increased in uH-Tx males but not in folate-treated males but tissue folate levels were unchanged. 5-Methylcytosine was significantly reduced in untreated and partially restored in treated individuals, while 5-hydroxymethylcytosine was not significantly changed. Similarly, a decrease in DNA-methyltransferase-1 expression in uH-Tx rats was partially reversed with treatment. The data expose a significant germline methylation error in unaffected adult male H-Tx rats from which hydrocephalic offspring are obtained. Reduced methylation in the testis and sperm was partially recovered by treatment with folate supplements leading us to conclude that this neurological disorder may not be completely eradicated by maternal supplementation alone.

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