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DNA damage in sperm alters Embryo Metabolism, finds study

Photo: Siddharth Kankaria

Science has established that the father’s sperm, which fertilizes the mother’s ovum resulting in the formation of an embryo, decides the sex of an individual. So it’s only logical that if the ‘male factor’ of the sperm/ovum relationship is damaged, the product will be too. Now, a recent collaborative study by a team of researchers led by Prof. Hanudatta Atreya of the Indian Institute of Science, Bangalore, and Prof. Satish Kumar Adiga of Kasturba Medical College, Manipal, has found that if the sperm, set to fertilize a particular ovum, has damaged DNA, it affects the metabolism of the embryo that it fathers. The study was conducted using samples of sperm and ova from couples undergoing Intra-Cytoplamic Sperm Injection (ICSI), a popular technique to help infertile couples conceive.

The study focussed on analysing the usage patterns of different amino acids, sugars and other nutrients, also called metabolites, by the embryos formed from damaged sperm cells. These observations performed using Nuclear Magnetic Resonance (NMR) – the same principle behind MRI scanners- were then compared with the metabolites used by embryos formed from healthy sperms. In addition, the study also analysed the differences in the nutrient requirements of embryos fertilized with healthy sperms and those with damaged DNA.  “These non-invasive biomarkers will now identify embryos with high amounts of DNA fragmentation and avoid transferring them to patients as they will eventually fail to implant or result in early pregnancy loss”, says Prof. Adiga explaining the importance of this study on assisted reproductive technologies.

During the study, the researchers subjected the collected sperm samples to a biochemical assay to visualize any defects present in the DNA and the damaged sperms were kept in a culture medium. They observed that the damaged sperms utilized metabolites to different extents than healthy samples. For example, they used more of glutamine, an amino acid, than healthy sperms. The researchers also used biochemical assays to study the differences in embryos conceived from normal and genetically abnormal sperms. The embryos formed from healthy sperms utilized more sugar (pyruvate) and less of the amino acid alanine.

Based on these observations, the researchers hypothesised that the differences in metabolite uptake in embryos from damaged and healthy sperms are probably efforts to correct the sperm mediated DNA damage to the embryo. After all, an embryo is DNA coding derived from its mother and father in equal parts! Ergo, it stands to reason that if 50% of its DNA has flaws, the embryo will do what it can to reverse or correct these flaws.

Though the study successful shows the resulting metabolic differences due to damaged DNA in sperms, it could not find a direct correlation between sperm DNA damage and the composition of the embryo since there is no currently available non-invasive technique to analyse the composition of embryos without damaging it.  Further research in this area could lead to a possible technique to analyse the embryo composition without destroying it.

“This study reinforces our belief that small molecule metabolites are valuable biomarkers of cellular conditions and the power of NMR spectroscopy in unravelling this information in a non-invasive manner,” asserts Prof. Atreya. The next step would be assisting the embryo to correct the DNA damage suffered from the hisperm or to do so in vitro, resulting in healthier embryos. Studies such as these lay foundation to a healthier society around us.