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Published on: February 6, 2018
Deficiency in mouse Y chromosome long arm gene complement is associated with sperm DNA damage
Yasuhiro Yamauchi1, Jonathan M Riel, Zoia Stoytcheva
1Institute for Biogenesis Research, John A Burns School of Medicine, University of Hawaii, 1960 East-West Rd, Honolulu, HI 96822, USA.
Background:
Mice with severe non-PAR Y chromosome long arm (NPYq) deficiencies are infertile in vivo and in vitro. We have previously shown that sperm from these males, although having grossly malformed heads, were able to fertilize oocytes via intracytoplasmic sperm injection (ICSI) and yield live offspring. However, in continuing ICSI trials we noted a reduced efficiency when cryopreserved sperm were used and with epididymal sperm as compared to testicular sperm. In the present study we tested if NPYq deficiency is associated with sperm DNA damage - a known cause of poor ICSI success.
Results:
We observed that epididymal sperm from mice with severe NPYq deficiency (that is, deletion of nine-tenths or the entire NPYq gene complement) are impaired in oocyte activation ability following ICSI and there is an increased incidence of oocyte arrest and paternal chromosome breaks. Comet assays revealed increased DNA damage in both epididymal and testicular sperm from these mice, with epididymal sperm more severely affected. In all mice the level of DNA damage was increased by freezing. Epididymal sperm from mice with severe NPYq deficiencies also suffered from impaired membrane integrity and abnormal chromatin condensation and suboptimal chromatin protamination. It is therefore likely that the increased DNA damage associated with NPYq deficiency is a consequence of disturbed chromatin remodeling.
Conclusions:
This study provides the first evidence of DNA damage in sperm from mice with NPYq deficiencies and indicates that NPYq-encoded gene/s may play a role in processes regulating chromatin remodeling and thus in maintaining DNA integrity in sperm.
Insights
Severe Y chromosome long arm (NPYq) deficiencies in mice lead to sperm DNA damage, impacting fertility and intracytoplasmic sperm injection (ICSI) success. This DNA damage is linked to impaired chromatin remodeling in NPYq-deficient sperm.
Area of Science:
- Reproductive Biology
- Genetics
- Sperm Biology
Background:
- Mice with severe non-PAR Y chromosome long arm (NPYq) deficiencies exhibit infertility.
- Previous studies showed ICSI success with malformed sperm, but reduced efficiency with cryopreserved and epididymal sperm.
- This study investigates the link between NPYq deficiency and sperm DNA damage, a known factor in ICSI failure.
Purpose of the Study:
- To determine if NPYq deficiency is associated with increased sperm DNA damage.
- To investigate the impact of NPYq deficiency on sperm quality and function relevant to ICSI.
- To explore the role of NPYq in chromatin remodeling and DNA integrity.
Main Methods:
- Analysis of epididymal and testicular sperm from NPYq-deficient mice.
- Intracytoplasmic sperm injection (ICSI) and oocyte activation assessment.
- Comet assays to evaluate sperm DNA damage.
- Assessment of membrane integrity, chromatin condensation, and protamination.
Main Results:
- NPYq-deficient epididymal sperm showed impaired oocyte activation, increased oocyte arrest, and paternal chromosome breaks post-ICSI.
- Comet assays revealed elevated DNA damage in both epididymal and testicular sperm, with epididymal sperm more affected.
- Freezing exacerbated DNA damage in all sperm samples.
- Epididymal sperm also exhibited compromised membrane integrity, abnormal chromatin condensation, and poor protamination.
Conclusions:
- This study is the first to demonstrate DNA damage in sperm from NPYq-deficient mice.
- NPYq-encoded genes likely play a crucial role in sperm chromatin remodeling.
- NPYq deficiency contributes to impaired DNA integrity in sperm, potentially explaining reduced ICSI efficiency.
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