Tuesday, August 6, 2013

MATERNAL DIABETES ALTERS EPIGENOME OF HER EGGS WHICH AFFECTS THE RESULTING EMBRYO

I have posted several times here about the consequences of a mothers dietary intake and weight status on the future health of her unborn child. There are numerous reports in the literature that clearly point to the fact that if a mother consumes a diet in excess of her caloric needs, her unborn child will have a significantly altered pattern of neurotransmitter expression related to the control of appetite and feeding behavior. In other word,s the child/children of an overweight/obese mother will have a strong innate desire to consume a diet of excess caloric need, will have a significant increase in the likelihood of becoming obese, and suffer the consequences of that inappropriate diet such as type 2 diabetes, hypertension, and cardiovascular disease. This very fact is resulting in an uncontrolled explosion in the obese population in the US and other industrialized nations who consume a typical "Western-style" diet particularly among adolescent children. 

A new report just published in the journal, Biology of Reproduction, presents further evidence linking maternal diabetes and epigenetic alterations in offspring due to changed in the expression of imprinted genes in oocytes (eggs).

Maternal Diabetes Causes Alterations of DNA Methylation Statuses of Some Imprinted Genes in Murine Oocytes

bit.ly/19DzUtb

This study examined the effects/consequences of maternal diabetes on the methylation status of several imprinted genes during embryonic development in laboratory mice. Imprinted genes are a class of genes whose expression pattern is dictated by the parental origin and this expression pattern is controlled by the methylation status of the imprinted gene, or in some cases to the alelle-specific state of histone methylation or acetylation. The first imprinted gene identified was the insulin-like growth factor 2 (IGF-2) gene. At least 80 genes are known to be imprinted in the human genome. Defects in the proper expression of numerous imprinted loci result in potentially devastating disorders.

You can read more about some of the most common imprinting diseases in the Diseases Associated with Genomic Imprinting page on themedicalbiochemistrypage.org

Many previous studies demonstrated that oocytes exposed to diabetic conditions during folliculogenesis exhibit negative effects related to maturation and developmental potential. Mitochondrial function, glucose metabolism pathways, and communications between cumulus cells and the oocyte are all changed in follicles of maternal diabetic mice.

In non-imprinted regions of the chromosomes, the parental epigenetic marks are erased in the germ cells only to be newly established in a parental-specific manner. Once the parental-specific epigenetic marks are established, they are maintained following fertilization. In contrast, imprinted genes exhibit what are referred to as differentially methylated regions (DMRs) and these DMRs escape the genome-wide demethylation that takes place during the earliest cleavage events of embryonic development. In addition, these DMRs escape the global de novo methylation that normally occurs when the embryo undergoes implantation. Two distinct types of DMRs have been found: those that are formed following fertilization and those that are formed in the germ cells and maintained throughout development. The latter DMRs are associated with chromosomal regions termed imprinting control centers, ICRs. Therefore, defects in the proper regulation of these DMRs can lead to profound consequences for the offspring resulting from fertilization of epigenetically altered oocytes and/or sperm.

This study examined the effects of maternal diabetes on the methylation status of two maternal genes Peg3 (a zinc-finger transcription factor originally identified as "paternally expressed gene 3") and Snrpn (small nuclear ribonucleoprotein polypeptide N). What this research discovered is that maternal diabetes altered the methylation status of Peg3 in a time-dependent manner. In othre words the changes become more pronounced the longer the female was diabetic. However, in this study the methylation status of Peg3 was not altered in the oocytes of female offspring.


So there is a bad-news good-news side to this research. The bad-news is that maternal diabetes has a negative effect on oocyte maturation and epigenetic status which results in negative consequences to oocyte maturation which can, in turn, result in negative developmental outcomes for offspring but the good-news is that the study did not find that the altered maternal oocyte epigenome was "transferred" to the female offspring oocyte epigenome.

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