Multigenerational analysis of sex-specific phenotypic differences at midgestation caused by abnormal folate metabolism
Abstract
The exposure to adverse environmental conditions (e.g. poor nutrition) may lead to increased disease risk in an individual and their descendants. In some cases, the results may be sexually dimorphic. A range of phenotypes has been associated with deficiency in or defective metabolism of the vitamin folate. However, the molecular mechanism linking folate metabolism to development is still not well defined nor is it clear whether phenotypes are sex-specific. The enzyme methionine synthase reductase (MTRR) is required for the progression of folate metabolism and the utilization of methyl groups from the folate cycle. Previously, we showed that the hypomorphicMtrrgtmutation in mice results in metabolic disruption, epigenetic instability, and a wide spectrum of developmental phenotypes (e.g. growth defects, congenital malformations) at midgestation that appear in subsequent wild-type generations. This transgenerational effect only occurs through the maternal lineage. Here, we explore whether the phenotypes that result from either intrinsic or ancestralMtrrdeficiency are sexually dimorphic. We found that no sexual dimorphism is apparent in either situation when the phenotypes were broadly or specifically defined. However, when we foc...Continue Reading
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DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos
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