Abstract
ABSTRACTSpermatozoa carry DNA damage that must be repaired by the oocyte machinery upon fertilization. Different strategies could be adopted by different vertebrates to face the paternal genotoxic damage. Mammals have strong sperm selection mechanisms and activate a zygotic DNA damage response (DDR) (including cell cycle arrest, DNA repair and alternative apoptosis) in order to guarantee the genomic conformity of the reduced progeny. However, external fertilizers, with different reproductive strategies, seem to proceed distinctively. Previous results from our group showed a downregulation of apoptotic activity in trout embryos with a defective DNA repairing ability, suggesting that mechanisms of tolerance to damaged DNA could be activated in fish to maintain cell survival and to progress with development. In this work, zebrafish embryos were obtained from control or UV-irradiated sperm (carrying more than 10% of fragmented DNA but still preserving fertilization ability). DNA repair (γH2AX and 53BP1 foci), apoptotic activity, expression of genes related to DDR and malformation rates were analyzed throughout development. Results showed in the progeny from damaged sperm, an enhanced repairing activity at the mid-blastula transition stage that returned to its basal level at later stages, rendering at hatching a very high rate of multimalformed larvae. The study of transcriptional and post-translational activity of tp53 (ZDF-GENE-990415-270) revealed the activation of an intense DDR in those progenies. However, the downstream pro-apoptotic factor noxa (ZDF-GENE-070119-3) showed a significant downregulation, whereas the anti-apoptotic gene bcl2 (ZDF-GENE-051015-1) was upregulated, triggering a repressive apoptotic scenario in spite of a clear genomic instability. This repression can be explained by the observed upregulation of p53 isoform Δ113p53, which is known to enhance bcl2 transcription. Our results showed that tp53 is involved in DNA damage tolerance (DDT) pathways, allowing the embryo survival regardless of the paternal DNA damage. DDT could be an evolutionary mechanism in fish: tolerance to unrepaired sperm DNA could introduce new mutations, some of them potentially advantageous to face a changing environment.
Highlights
Sexual reproduction is a key evolutionary event allowing the combination of genetic information from two progenitors for giving rise to a newborn
The embryo acquires a greater ability to generate an integral DNA damage response (DDR), activating different genes involved in the detection of DNA damage, in different DNA repairing pathways, in the control of cell cycle arrest and in the apoptotic activity (Jaroudi and Sengupta, 2007)
Genotoxic damage in sperm The analysis of cells with different degree of DNA damage using the comet assay showed that UV irradiation significantly increased DNA fragmentation
Summary
Sexual reproduction is a key evolutionary event allowing the combination of genetic information from two progenitors for giving rise to a newborn. Fertilization with DNA-damaged sperm (DDS) seems to activate some mechanisms of cell cycle arrest at zygotic G2/M and to increase the activity of different repairing pathways immediately after fertilization (mainly BER, MMR and HR pathways) (Chen et al, 2012; González-Marín et al, 2012; Jaroudi and Sengupta, 2007; Kumar et al, 2013; Wang et al, 2013). The embryo acquires a greater ability to generate an integral DDR, activating different genes involved in the detection of DNA damage, in different DNA repairing pathways, in the control of cell cycle arrest and in the apoptotic activity (Jaroudi and Sengupta, 2007). Zebrafish share with mammals the DNA repairing pathways, cell cycle control mechanisms and the main apoptotic pathways
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
