Accumulating evidences showed that thyroid hormone was participated in the functioning of the reproductive system, and an elevated level of thyroid hormones had a negative impact on reproductive system. However, the molecular basis for this observation still remains to be fully understood. Here, we show that l-Thyroxine significantly impaired human sperm motility. The molecular basis showed that thyroxine receptor stimulation triggers Phosphatidyl Inositol 3-kinase (PI3K)/Akt signaling activation leading to the E3 ligase MDM2 phosphorylation at serine 166, which directly interacted with p53 for degradation. p53 degradation caused a p53-dependent DNA damage checkpoint or repair dysfunction, which eventually results in DNA damage accumulation in sperm. Our results highlight that inhibition of PI3K/Akt pathway or p53 degradation is important in maintaining sperm motility in a thyroxine receptor (TR)-dependent manner.
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| http://dx.doi.org/10.1016/j.gene.2017.03.014 | DOI Listing |
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