Journal
CONGENITAL ANOMALIES
Volume 55, Issue 3, Pages 133-144Publisher
WILEY-BLACKWELL
DOI: 10.1111/cga.12113
Keywords
assisted reproductive technologies; DNA methylation; genomic imprinting; genomic imprinting disorders; male infertility
Categories
Funding
- Ministry of Health, Labour and Welfare of the Japanese Government [26310301]
- Scientific Research (KAKENHI) [25670691, 24613001, 26870036, 26870033]
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [24613001, 26870033, 25670691, 26310301, 26870036] Funding Source: KAKEN
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The most common form of male infertility is a low sperm count, known as oligozoospermia. Studies suggest that oligozoospermia is associated with epigenetic alterations. Epigenetic alterations in sperm, which may arise due to the exposure of gametes to environmental factors or those that pre-exist in the sperm of infertile individuals, may contribute to the increased incidence of normally rare imprinting disorders in babies conceived after assisted reproductive technology using the sperm of infertile men. Genomic imprinting is an important developmental process whereby the allelic activity of certain genes is regulated by DNA methylation established during gametogenesis. The aberrant expression of several imprinted genes has been linked to various diseases, malignant tumors, lifestyle and mental disorders in humans. Understanding how infertility and environmental factors such as reproductive toxicants, certain foods, and drug exposures during gametogenesis contribute to the origins of these disorders via defects in sperm is of paramount importance. In this review, we discuss the association of epigenetic alterations with abnormal spermatogenesis and the evidence that epigenetic processes, including those required for genomic imprinting, may be sensitive to environmental exposures during gametogenesis, fertilization and early embryonic development. In addition, we review imprinting diseases and their relationships with environmental factors. While the plasticity of epigenetic marks may make these more susceptible to modification by the environment, this also suggests that aberrant epigenetic marks may be reversible. A greater understanding of this process and the function of epidrugs may lead to the development of new treatment methods for many adult diseases in the future.
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