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DNA METHYLATION PROGRAMMING TO OOCYTE ENVIRONMENT

Award Number: U01HD044638
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2005
PERIOD OF PERFORMANCE END DATE: 08/31/2007

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DNA METHYLATION PROGRAMMING TO OOCYTE ENVIRONMENT - DESCRIPTION (provided by applicant): This proposal will test the hypothesis that maternal nutritional effects in developing oocytes and procedures used in assisted reproduction (ART) can program fetal development and adult health via heritable epigenetic changes in DNA methylation at specific gene loci in the oocyte and pre-implantation embryo. It will utilize two well established animal models of pre-and postnatal development to determine the effects of methionine-deficient (hypomethylation) diets offered during the period of oocyte growth and maturation, and pre-implantation embryo development on: (i) pre- and postnatal development, (ii) genome wide alterations in DNA methylation, and methylation of specific loci on imprinted genes in fetal and placental tissues, and (iii) methylation of imprinted and non-imprinted loci in oocytes and pre-implantation embryos. In addition, the effects of dietary treatment on oocyte DNA methylation with and without gonadotrophin stimulation (super ovulation) will be examined. Changes in oocyte methylation status will be correlated to indices of methylation cycle activity (e.g., S-adenosyl methionine/S-adenosyl homocysteine ratio) in granulosa cells and follicular fluid; and related to genetic allelic variations in methyl donor group enzymes. Finally, additional effects of culturing zygotes from FSH-stimulated donor animals from different dietary backgrounds in the presence or absence of serum on DNA methylation in pre-implantation embryos will be complemented by assessing effects on fetal and postnatal development. Zygotes and embryos will be collected from sheep offered either a methionine deficient or supplemented diet and transferred to surrogate dams. Rats offered either control or hypomethylating diets will revert to control diets at a similar stage of pregnancy (Day 4 post fertilization). Fetal tissues will be harvested for analysis at specific points of gestation. Some fetuses will be taken to term, and post-natal measurements of growth and development determined (by X-ray CT in the case of sheep). Insulin resistance, blood pressure and immune function will be determined in adult rats. Defining the effects of diet and ART on DNA methylation within the oocyte, as well as genotype variations and DNA methyltransferase gene expression, will provide novel markers for defining oocyte programming of specific future phenotypes in ART, and form the basis for establishing appropriate nutritional intervention in the periconception period.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2007 ( Subtotal = $103,836 )
2007	2007	UNIVERSITY OF NOTTINGHAM	**	NOTTINGHAM		00000		GBR	Child Health and Human Development Extramural Research	001	3	1/9/2007	SUPPLEMENT FOR EXPANSION	$103,836
														Subtotal = $103,836

Issue Date FY: 2004 ( Subtotal = $311,767 )
2004	2004	SCOTTISH AGRICULTURAL COLLEGE						UK	Population Research	000	2	9/23/2004	NON-COMPETING CONTINUATION	$311,767
														Subtotal = $311,767

Issue Date FY: 2003 ( Subtotal = $295,156 )
2003	2003	SCOTTISH AGRICULTURAL COLLEGE						UK	Population Research	000	1	9/26/2003	NEW	$295,156
														Subtotal = $295,156

Grand Total All Awards = $710,759

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DNA METHYLATION PROGRAMMING TO OOCYTE ENVIRONMENT

Award Number: U01HD044638

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2005

PERIOD OF PERFORMANCE END DATE: 08/31/2007

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