Fertilization and epigenetics in mammals

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Contributions of mammalian females to their offspring are apparent–both nuclear and mitochondrial DNA, for example, as well as exposure to various factors during gestation, the research focused on male contribution. Looking at the differences between sperm removed directly from the testicles and ejaculated sperm, to investigate whether these differences may have an impact on the long-term health of the offspring.

The studies looked at small RNAs to determine how these molecules contribute to epigenetic changes in sperm in mice. In the first study, led by Upasna Sharma, PhD, postdoctoral fellow at UMMS, the investigators looked at what happens to small RNAs when sperm leave the testes and travel through the epididymis toward the vas deferens, a process that takes about two weeks. Researchers found that the sperm underwent dramatic changes to its their RNA “payload” – small RNAs carrying information -during this time. They confirmed that some of the RNA found in sperm originates in the paternal epididymis and is later transferred to sperm cells.

The second study looked at the functional implications of small RNAs in sperm and whether these small RNAs have any effect on sperm or the fertilized egg. The team, led by UMMS Postdoctoral Associate Colin C. Conine, PhD, found that small RNAs in sperm are essential for normal pre-implantation development. Specifically, they showed that embryos fertilized using sperm from early in the epididymis- where sperm have not yet gained a full payload of regulatory RNAs exhibit gene misregulation early in development and then fail to implant in the uterus efficiently.

The researchers could correct these defects by injecting small RNAs from the end of the epidydimal pathway into the newly formed embryo. Paternal environmental conditions can affect the health of offspring and that a man’s lifestyle and exposure to potentially hazardous elements like stress and toxins can affect the levels and types of small RNA in the sperm.

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