Ontogeny-Driven rDNA Rearrangement, Methylation, and Transcription, and Paternal Influence

Gene rearrangement occurs during development in some cell types and this genome dynamics is modulated by intrinsic and extrinsic factors, including growth stimulants and nutrients. This raises a possibility that such structural change in the genome and its subsequent epigenetic modifications may also take place during mammalian ontogeny, a process undergoing finely orchestrated cell division and differentiation. We tested this hypothesis by comparing single nucleotide polymorphism-defined haplotype frequencies and DNA methylation of the rDNA multicopy gene between two mouse ontogenic stages and among three adult tissues of individual mice. Possible influences to the genetic and epigenetic dynamics by paternal exposures were also examined for Cr(III) and acid saline extrinsic factors. Variables derived from litters, individuals, and duplicate assays in large mouse populations were examined using linear mixed-effects model. We report here that active rDNA rearrangement, represented by changes of haplotype frequencies, arises during ontogenic progression from day 8 embryos to 6-week adult mice as well as in different tissue lineages and is modifiable by paternal exposures. The rDNA methylation levels were also altered in concordance with this ontogenic progression and were associated with rDNA haplotypes. Sperm showed highest level of methylation, followed by lungs and livers, and preferentially selected haplotypes that are positively associated with methylation. Livers, maintaining lower levels of rDNA methylation compared with lungs, expressed more rRNA transcript. In vitro transcription demonstrated haplotype-dependent rRNA expression. Thus, the genome is also dynamic during mammalian ontogeny and its rearrangement may trigger epigenetic changes and subsequent transcriptional controls, that are further influenced by paternal exposures

Chronic kidney disease and nutrition support.

Individuals with chronic kidney disease (CKD), particularly those undergoing maintenance dialysis, are prone to protein-energy wasting (PEW), the latter of which can be ameliorated with different methods of nutrition support. Dietary counseling guided by dietitians is the key for preventing and managing PEW in CKD. If dietary counseling per se fails to meet the recommended energy and protein requirements, the addition of oral nutrition supplements (ONSs) would be necessary. When these initial measures cannot attain the recommended energy and protein requirements, nutrition support, including enteral tube feeding or parenteral nutrition (PN), should be considered as a viable option to improve nutrition status. Partial PN, comprising intraperitoneal PN (IPPN) and intradialytic PN (IDPN) therapies, may be attempted as supplemental nutrition support in patients with PEW requiring peritoneal dialysis and hemodialysis, respectively. Despite the debatable effectiveness of IPPN for patients undergoing peritoneal dialysis, it remains a feasible means in these patients. The indications for IPPN in patients undergoing peritoneal dialysis include inadequate dietary intake of energy and protein, and barriers of oral intake and other forms of enteral supplementation such as issues with suitability, tolerance, and compliance. Nonetheless, in the case of spontaneous dietary consumption of energy and protein meeting the difference between the IDPN provision and the nutrition targets, the use of IDPN is rational. In patients with PEW and malfunctioning gastrointestinal tract, as well as those whose enteral intake (with or without partial PN) is below the recommended nutrient requirements, total PN becomes a relevant nutrition intervention