DNA repair decline during mouse spermiogenesis results in the accumulation of heritable DNA damage.

  title={DNA repair decline during mouse spermiogenesis results in the accumulation of heritable DNA damage.},
  author={Francesco Marchetti and Andrew J Wyrobek},
  journal={DNA repair},
  volume={7 4},

DNA repair efficiency in germ cells and early mouse embryos and consequences for radiation-induced transgenerational genomic damage

There is growing evidence that implicates DNA damage carried by the fertilizing gamete as a mediator of postfertilization processes that contribute to genomic instability in subsequent generations.

Paternal DNA damage resulting from various sperm treatments persists after fertilization and is similar before and after DNA replication.

Evidence is provided that subjecting sperm to DNA damage-inducing treatments results in degradation of highly condensed sperm chromatin when it is still packed within the sperm head, and that this DNA damage persists after fertilization.

Oxidative stress in sperm affects the epigenetic reprogramming in early embryonic development

It is shown that fertilization using sperm exposed to oxidative stress caused a major developmental arrest at the time of embryonic genome activation and the recruitment of XRCC1 to damaged paternal pronuclei indicates that oxidative DNA lesions drive BER to repair DNA at the expense of DNA demethylation.

Direct and delayed X‐ray‐induced DNA damage in male mouse germ cells

The results suggest that proliferating spermatogonia retain a memory of the radiation insult that is recognized at a later developmental stage and activates a process leading to DNA fragmentation.

DNA Double Strand Break Response and Limited Repair Capacity in Mouse Elongated Spermatids

The genetic mutant analysis suggests that an incomplete or defective meiotic recombinational repair of Spo11-induced DSBs may lead to a carry-over of the DSB damage or induce a delayed nuclear fragmentation during the sensitive programmed chromatin remodeling occurring in elongated spermatids.

Meiotic interstrand DNA damage escapes paternal repair and causes chromosomal aberrations in the zygote by maternal misrepair

Treatment of male mice with melphalan, a bifunctional alkylating agent widely used in chemotherapy, induces DNA lesions during male mouse meiosis that persist unrepaired as germ cells progress through DNA repair-competent phases of spermatogenic development, highlighting the importance of both pre- and post-fertilization DNA repair in assuring the genomic integrity of the conceptus.

Assessment of Sperm DNA Integrity and Implications for the Outcome of ICSI Treatments

Damage to sperm DNA is likely to result in poor implantation rates or miscarriage, and therefore leads to a reduction in clinical pregnancy rates and the repair by the oocyte may result in malformations or diseases in the offspring.

Rad54/Rad54B deficiency is associated to increased chromosome breakage in mouse spermatocytes

The results provide the first evidence of the role of Rad54/Rad54B in the maintenance of a stable karyotype during male meiosis, and suggest that Rad54-deficient animals may impact on the DNA integrity of developing mouse gametes.

Genetic Instability and Chromatin Remodeling in Spermatids

It is proposed that the chromatin remodeling in spermatids offers a proper context for the induction of de novo polymorphism and structural variations that can be transmitted to the next generation.



Disruption of maternal DNA repair increases sperm-derived chromosomal aberrations

It is demonstrated that mutagenic exposures during late spermatogenesis can induce damage that persists for at least 7 days in the fertilizing sperm and that maternal genotype plays a major role in determining the risks for pregnancy loss and frequencies of offspring with chromosomal defects of paternal origin.

Stimulation of DNA repair by the spermatidal TP1 protein

It is reported that TP1 can stimulate the repair of SSB in vitro and demonstrated that in vivo repair of UV‐induced DNA lesions is enhanced in mammalian cells stably expressing TP1.


During the chromatin remodeling in spermatids, the combined DNA-condensing activities provided by the basic transition proteins and protamines may optimize the strand repair process emphasizing the link between altered sperm DNA condensation and DNA fragmentation.

Changes in X-ray sensitivity of mouse eggs from fertilization to the early pronuclear stage, and their repair capacity.

The analysis of potentiation effects of 3-aminobenzamide and caffeine on the yield of X-ray-induced chromosome aberrations demonstrated that the increase of radiosensitivity and the decrease of chromosome-type exchange induction with pronuclear formation, may be closely correlated with alterations in chromatin configuration in the pronuclei and in repair capacity of fertilized eggs at the pre-DNA-synthetic stage.

Etoposide induces heritable chromosomal aberrations and aneuploidy during male meiosis in the mouse

It is found that therapeutic doses of etoposide affect primarily meiotic germ cells, producing unstable structural aberrations and aneuploidy, effects that are transmitted to the progeny.

How do male germ cells handle DNA damage?

Induction of chromosomal aberrations in mouse zygotes by acrylamide treatment of male germ cells and their correlation with dominant lethality and heritable translocations

Findings indicate that PAINT/DAPI analysis of zygotic metaphases is a promising method for detecting male germ cell mutagens capable of inducing chromosomal aberrations and for evaluating the associated risks for embryonic loss and balanced translocations at birth.