Sperm Chromosome Research Articles

Reproductive genetics and the aging male.

To examine current evidence of the known effects of advanced paternal age on sperm genetic and epigenetic changes and associated birth defects and diseases in offspring. Review of published PubMed literature. Advanced paternal age (> 40years) is associated with accumulated damage to sperm DNA and mitotic and meiotic quality control mechanisms (mismatch repair) during spermatogenesis. This in turn causes well-delineated abnormalities in sperm chromosomes, both numerical and structural, and increased sperm DNA fragmentation (3%/year of age) and single gene mutations (relative risk, RR 10). An increase in related abnormalities in offspring has also been described, including miscarriage (RR 2) and fetal loss (RR 2). There is also a significant increase in rare, single gene disorders (RR 1.3 to 12) and congenital anomalies (RR 1.2) in offspring. Current research also suggests that autism, schizophrenia, and other forms of "psychiatric morbidity" are more likely in offspring (RR 1.5 to 5.7) with advanced paternal age. Genetic defects related to faulty sperm quality control leading to single gene mutations and epigenetic alterations in several genetic pathways have been implicated as root causes. Advanced paternal age is associated with increased genetic and epigenetic risk to offspring. However, the precise age at which risk develops and the magnitude of the risk are poorly understood or may have gradual effects. Currently, there are no clinical screenings or diagnostic panels that target disorders associated with advanced paternal age. Concerned couples and care providers should pursue or recommend genetic counseling and prenatal testing regarding specific disorders.

Impact of a mild scrotal heating on sperm chromosomal abnormality, acrosin activity and seminal alpha-glucosidase in human fertile males.

The aim of this study was to observe sperm aneuploidy, DNA integrity, seminal alpha-glucosidase (NAG) and acrosin activity (AA) under testicular heat stress (SH). Spermatozoa were obtained from 30 healthy adult volunteers subjected to scrotal warming at 43°C for 30-40min on two successive days per week for 3months between February 2012 and September 2016. Aniline blue (AB), acridine orange (AO) staining, TUNEL assay and FISH analysis to evaluate sperm function, sperm DNA integrity and chromosomal abnormalities were carried on before, during and after SH. Sperm AA and NAG was measured by microplate reader. The mean parameters of sperm parameters, AA and NAG were significantly decreased. In contrast, the mean percentage of sperm DNA fragmentation and the proportion of aneuploidy of chromosomes 13, 18, 21, X and Y were significantly increased for spermatozoa collected during SH versus before SH (p<.01-.001). After stopping scrotal heating for 3months, most parameters were completely restored to pre-SH levels. Sperm parameters, sperm DNA integrity, chromosomes, AA and NAG are affected by scrotal exposure to constant SH temperatures several degrees over normal physiological temperature, and after treatment, these parameters were reversibly restored to the level before SH in adult men.

Assessment of male factor involved in recurrent pregnancy loss: A preliminary study

Abstract This study was conducted to assess the male factor as standard sperm parameters, age and chromosome abnormalities from men whose partners had a history of recurrent pregnancy loss (RPL). A 2 years retrospective study was carried out in 149 couples with 2 or more miscarriages. They referred to as for genetic counseling in the laboratory of histology housed in a Faculty of Medicine of Sfax, with genetic laboratories. Chromosomal analysis was performed using RHG banding in peripheral blood and semen samples were analyzed from men according to World Health Organization guidelines. 67 men were selected of a total of 149 couples whose partners were healthy and with normal karyotype. About them, the mean age was 33 years [from 22 to 53], and altered semen parameters were detected in more than 25%. Abnormal karyotype was detected in 4 men with an overall incidence of 5.97%. The commonest abnormalities appear to be reciprocal translocation. So, this data emphasizes the importance of assessment of male factor in addition to standard female factors for evaluating the risk for RPL.

Air Pollution and Human Sperm Sex Ratio.

The present study was designed to address the hypothesis that exposure to specific air pollutants may impact human sperm Y:X chromosome ratio. The study population consisted of 195 men who were attending an infertility clinic for diagnostic purposes and who had normal semen concentration of 15–300 mln/ml (WHO, 2010). Participants represented a subset of men in a multicenter parent study conducted in Poland to evaluate environmental factors and male fertility. Participants were interviewed and provided a semen sample. The Y:X ratio was assessed by fluorescent in situ hybridization (FISH). Air quality data were obtained from the AirBase database. In multivariate analysis the significant reduction was observed in the proportion of Y/X chromosome bearing sperm and exposure to particulate matter >10 μm in aerodynamic diameter PM10 (p = .009) and particulate matter <10 μm in aerodynamic diameter PM2.5 (p = .023). The observed effects of a lower Y:X sperm chromosome ratio among men exposed to air pollution support the evidence that the trend of declining sex ratio in several societies over past decades has been due to exposure to air pollution; however due to limited data on this issue, the obtained results should be confirmed in longitudinal studies.

The Inability of Human Sperm with Chromosomal Abnormalities to Penetrate the Oocyte in Assisted Reproductive Technology (ART): Risk Factors and the Role of Seminal Plasma

Abstract: The combination of ICSI and a sperm chromosome assay provides a useful opportunity to directly investigate relationships between chromosomal aberrations and head morphology, motility or in vitro aging. An increase of aneuploidy was identified in sperm with large heads. Structural chromosome aberrations were frequently found in elongated heads. These types of sperm should therefore be avoided for ICSI and can easily be identified under a microscope. In sperm with normal heads, the chromosomal aberration rate was initially low but increased gradually after removal of the seminal plasma (3.3% to 15.9%); in immotile sperm, the increase of DNA damage was more pronounced (4.5% to 48.1%). Therefore, there are motile and immotile sperm populations in human ejaculates that are potentially vulnerable to in vitro culture conditions. Since these sperm can maintain DNA integrity in the seminal plasma for at least 3 h, and even after cryopreservation, the seminal plasma appears to be an efficient suppressor o...

Prevention of high-temperature-induced chromosome damage in mouse spermatozoa freeze-dried using Ca2+ chelator-containing buffer alkalinized with NaOH or KOH

In order to protect sperm chromosomes against degradation when they are being stored for relatively high temperatures, we investigated the optimal pH of the freeze-drying solution, EGTA/Tris-HCl buffered solution alkalinized by NaOH (Na-ETBS) or KOH (K-ETBS). Mouse spermatozoa suspended in Na-ETBS or K-ETBS were freeze-dried at pH 5.0–8.4 and stored at 4 °C or 50 °C for 3 days. Some freeze-dried samples were stored at 25 °C for 3 days or 1 month. After storage, samples injected into oocytes using intracytoplasmic sperm injection were assessed for chromosome damage in resulting zygotes. Irrespective of freeze-drying solutions and storage temperatures, almost all the zygotes (97–100%) produced using the spermatozoa freeze-dried at pH 5.0 had structural chromosome aberrations of sperm origin. When freeze-drying was conducted at pH 8.0–8.4 using Na-ETBS, the incidence of chromosome damage decreased to 14–17% in 4 °C storage and 24–26% in 50 °C storage. When freeze-dried in K-ETBS, the lowest level of chromosome damage occurred at pH levels of 7.7–8.4 at 4 °C storage (13–15%) and at pH 7.7–8.0 at 50 °C storage (16–23%). Spermatozoa freeze-dried in Na-ETBS at pH 8.2 and K-ETBS at pH 7.7 showed no significant increase in chromosome damage during 25 °C storage from 3 days to 1 month (11%–20% in Na-ETBS; 13%–18% in K-ETBS). Thus, use of the solutions optimized for short-term storage at high temperature (50 °C, 3 days) permits prolonged storage (1 month) of freeze-dried spermatozoa at room temperature.

Environmental exposure to parabens and sperm chromosome disomy

Parabens are widely used as antimicrobial preservatives in cosmetics, pharmaceuticals, food and beverage processing due to their board spectrum of activity, inertness, and low cost. The study population consisted of 156 men under 45 years of age who attended the infertility clinic for diagnostic purposes with normal semen concentration of 15–300 mln/ml. Participants were interviewed and provided a semen sample. The parabens concentrations: ethyl paraben (EP), butyl paraben (BP), methyl paraben (MP), and iso-butyl paraben (iBuP) were analyzed in the urine using a validated gas chromatography ion-tap mass spectrometry method. The positive association was found between urinary level of BP and XY18 disomy (p = 0.045) and PP and disomy of chromosome 13 (p = 0.007). This is the first study to examine these relationships, and replication of our findings is needed before the association between parabens concentration in urine and aneuploidy can be fully defined. These findings may be of concern due to increased parabens use.

Sperm aneuploidy after testicular cancer treatment: data from a prospective multicenter study performed within the French Centre d’Étude et de Conservation des Oeufs et du Sperme network

To study sperm aneuploidy in a population of testicular cancer (TC) patients treated with the use of either bleomycin-etoposide-cisplatin (BEP) chemotherapy or radiotherapy. Multicenter prospective longitudinal study of TC patients analyzed before treatment and after 3, 6, 12, and 24months (T3-T24). Fifty-four TC patients and a control group of 10 fertile sperm donors. University hospital laboratories. Routine semen analyses; sperm aneuploidy and diploidy. Comparison of sperm characteristics and sperm chromosome abnormalities during TC patient follow-up. Semen characteristics recovered pretreatment values 12months after radiotherapy and 24months after more than two BEP cycles. A significant increase in sperm disomy YY and XX was observed in the TC group before treatment compared with the control group. After more than two BEP cycles, the mean sperm aneuploidy rate increased significantly at T12 and reached the pretreatment value at T24. After radiotherapy, the mean sperm aneuploidy returned to the pretreatment value at T12. At T24, nearly 40% of TC patients did not recover their pretreatment sperm aneuploidy rate. Genetic counseling of TC patients should include information on the potential elevated risk of aneuploid conceptus from sperm recovered after treatment and the necessity to postpone conception up to ≥12months after radiotherapy and ≥24months after more than two BEP chemotherapy cycles. However, few men receiving one or two BEP cycles and some dropouts are the main limitations of this study.

Impact of Hodgkin or non-Hodgkin lymphoma and their treatments on sperm aneuploidy: a prospective study by the French CECOS network

To assess sperm production and aneuploidy in Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) before and after treatments. Multicenter, prospective, longitudinal study of lymphoma patients analyzed before treatment and after 3, 6, 12, and 24months. University hospitals. Forty-five HL and 13 NHL patients were investigated before and after treatment. Treatment regimens were classified in two groups: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) with or without (±) radiotherapy, and CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)/MOPP-ABV (mechlorethamine, oncovin, procarbazine, prednisone-doxorubicin, bleomycin, vinblastine). A control group of 29 healthy men was also studied. Semen analyses and aneuploidy study by FISH were performed at each time point. Comparison of mean sperm characteristics and percentage of sperm aneuploidy rates before and after treatment. Before treatment, HL and NHL men had altered semen characteristics and higher sperm aneuploidy rates (median 0.76 [interquartile range 0.56-0.64]) than the control group (0.54 [0.46-0.74]). After treatment, sperm production was significantly lowered 3 and 6months after ABVD ± radiotherapy or CHOP/MOPP-ABV. After ABVD ± radiotherapy, the aneuploidy rate increased significantly only at 3months, and values obtained 1 or 2years later were lower than pretreatment values. In contrast, in the CHOP/MOPP-ABV treatment group, semen characteristics and aneuploidy rate did not return to normal levels until 2years after treatment. Lymphoma itself has consequences on sperm aneuploidy frequency before treatment. Moreover, lymphoma treatments have deleterious effects on sperm chromosomes related to treatment type and time since treatment. Patient counseling is essential concerning the transient but significant sperm aneuploidy induced by lymphoma and its treatments.

Polychlorinated biphenyls and dibenzofurans increased abnormal sperm morphology without alterations in aneuploidy: The Yucheng study

In 1979, more than 2000 persons ingested rice oil contaminated with polychlorinated biphenyls and polychlorinated dibenzofurans; this event was called the “Yucheng accident.” An increased percentage of oligospermia, reduced ability of sperm to penetrate oocytes, and reduced percentage of male offspring were reported in Yucheng men. This study examined whether the sperm sex ratio and chromosome aneuploidy are responsible for our observed findings in Yucheng men. In 1999–2000, Yucheng men and their neighborhood referents aged 37–50 years were recruited for physical examination, followed by semen analysis. The semen samples were analyzed for chromosomal aneuploidy through fluorescent in situ hybridization according to an established procedure in our laboratory. A total of 50 Yucheng men and 34 neighborhood referents volunteered to participate in the study. Although abnormal morphology was mildly increased, no differences were observed in sperm percentages, with normal numbers of chromosomes X, Y, and 8 in the two groups. The percentage of sperm with aneuploidy of the sex chromosomes or chromosome 8 and of that with diploidy did not vary between both groups. The normal X/Y sperm ratio was not different between the groups. However, among Yucheng men, 8% had a normal X/Y sperm ratio of >1.4, and no neighborhood referent showed such an elevated X/Y ratio. Chromosomal aneuploidy was not elevated in Yucheng men. The mechanisms underlying the reduced sperm capability of oocyte penetration and changed offspring sex ratio in Yucheng men remain undetermined.

Spermatozoa from infertile patients exhibit differences of DNA methylation associated with spermatogenesis-related processes: an array-based analysis

The influence of aberrant sperm DNA methylation on the reproductive capacity of couples has been postulated as a cause of infertility. This study compared the DNA methylation of spermatozoa of 19 fertile donors and 42 infertile patients using the Illumina 450K array. Clustering analysis of methylation data arranged fertile and infertile patients into two groups. Bivariate clustering analysis identified a differential distribution of samples according to the characteristics of seminogram and age, suggesting a possible link between these parameters and specific methylation profiles. The study identified 696 differentially methylated cytosine-guanine dinucleotides (CpG) associated with 501 genes between fertile donors and infertile patients. Ontological enrichment analysis revealed 13 processes related to spermatogenesis. Data filtering identified a set of 17 differentially methylated genes, some of which had functions relating to spermatogenesis. A significant association was identified between RPS6KA2 hypermethylation and advanced age (P = 0.016); APCS hypermethylation and oligozoospermia (P = 0.041); JAM3/NCAPD3 hypermethylation and numerical chromosome sperm anomalies (P = 0.048); and ANK2 hypermethylation and lower pregnancy rate (P = 0.040). This description of a set of differentially methylated genes provides a framework for further investigation into the influence of such variation in male fertility in larger patient cohorts.

Euploid blastocyst transfer is a viable clinical option for male factor infertility with high sperm DNA fragmentation

A significant association has been reported between sperm DNA fragmentation and sperm chromosome abnormalities. The objective of this study was to evaluate the clinical efficacy of euploid frozen blastocyst transfer for male factor (MF) infertility patients with high sperm DNA fragmentation.

Association of gene polymorphisms of folate metabolism with sperm aneuploidy in men with low reproductive function

Aim. The association of polymorphic variants of genes MTHFR (C677T, A1298C) and MTRR (A66G) with sperm aneuploidy in men with low reproductive function was investigated. Methods. SNPs determinations were performed by the real-time PCR technique. Sperm DNA fragmentation analysis was performed using the method of sperm chromatin dispersion. To detect aneuploidy in spermatozoa nuclei the method of fluorescent in situ hybridization (FISH) was used. Results. Polymorphic alleles in genes of folate metabolism are associated with sperm aneuploidy in men with low reproductive function. The link between the number of alternative alleles of polymorphic variants A1298C of MTHFR gene in genotype and the average level of aneuploidy in sperm chromosome 16 is proved.Conclusion. Aneuploid sperm is able to fertilize the oocytes, but the further formation of the blastocyst and embryo implantation may be blocked at various stages of development. Understanding the genetic basis of aneuploidy in sperm of men could reduce the reproductive losses in IVF practice.Keywords: DNA fragmentation, sperm aneuploidy, MTHFR, MTRR, reproductive function.

The ability to gain matings, not sperm competition, reduces the success of males carrying a selfish genetic element in a fly

Females are expected to avoid low-quality males fathering their offspring. X chromosome meiotic drive (XCMD) makes males very low-quality mates. XCMDs are X chromosomes that, in males, cause the failure of all Y chromosome sperm, so all functional sperm carry the driving X and produce daughters. This transmission advantage can allow the XCMD to spread through populations. However, XCMD males typically have low fertility, are very poor at sperm competition, only produce daughters, and bear low fitness alleles associated with XCMD. This imposes significant costs on females that mate with these males. Recently, several studies have shown that females can reduce the risk of their offspring inheriting XCMDs by mating with multiple males (polyandry), as XCMD males typically lose out to normal males in sperm competition. Hence it has been suggested that increased polyandry may be likely to evolve whenever a costly XCMD is common in a population, and that polyandry may be a key factor in preventing XCMDs spreading through populations. We tested this by examining the fruit fly Drosophila subobscura, in which females are known to mate only once in European populations where XCMDs are absent. However, in North African populations an XCMD, referred to as ‘SRs’, occurs. If the association between XCMDs and polyandry is true, then these North African populations should have evolved polyandry. However, we found no evidence of polyandry in North African D. subobscura populations. Instead, we found some evidence that males that carry SRs are slightly less successful at gaining matings in noncompetitive situations. These results show that polyandry does not necessarily evolve in response to the presence of harmful X chromosome drive. With both sperm competition and female choice both being unlikely to substantially reduce the success of XCMD in D. subobscura, the factors that prevent SRs spreading through these populations remain mysterious.

Exposure to widespread environmental endocrine disrupting chemicals and human sperm sex ratio

In recent years, a trend toward a declining proportion of male births has been noted in several, but not all, industrialized countries. The underlying reason for the drop in the sex ratio is unclear, but one theory states that widespread environmental endocrine disrupting chemicals affecting the male reproductive system in a negative manner could be part of the explanation. The present study was designed to investigate whether the urinary phthalate, pyrethroids and polycyclic aromatic hydrocarbons metabolites concentrations were associated with sperm Y:X ratio.The study population consisted of 194 men aged under 45 years of age who attended infertility clinic in Lodz, Poland for diagnostic purposes with normal semen concentration of 20–300 mln/ml or with slight oligozoospermia (semen concentration of 15–20 mln/ml) (WHO, 1999). The Y:X ratio was assessed by fluorescent in situ hybridization. Urinary concentrations of 1-hydroxypyrene were measured by high performance liquid chromatography, phthalate metabolites were analyzed using a procedure based on the LC-MS/MS methods and metabolites of synthetic pyrethroids were assessed by gas chromatography ion-tap mass spectrometry method.After adjustment for potential confounders (past diseases, age, abstinence, smoking, alcohol consumption, sperm concentration, motility, morphology) 5OH MEHP, CDCCA to TDCCA and 1-OHP was negatively related to Y:X sperm chromosome ratio (p = 0.033, p < 0.001, p = 0.047 respectively).As this is the first study to elucidate the association between the level of metabolites of widespread environmental endocrine disrupting chemicals (phthalates, synthetic pyrethroids, polycyclic aromatic hydrocarbons) on sex chromosome ratio in sperm therefore, these findings require further replication in other populations.

Effects of Hepatitis C Virus Infection on Human Sperm Chromosomes

To determine the degree of chromosomal aberrations in the sperm of men with hepatitis C. 36 subjects (20 in the healthy control group and 16 in the HCV infection group [genotype 1b]) were recruited. The cause of viral transmission was unknown in all patients. Sperm samples from the subjects were used for interspecies in vitro fertilization of zona-free golden hamster ova. The frequencies of spermatozoan aberrations were compared between the healthy control group and the HCV infection group. A total of 280 sperm chromosome complements were studied, including 129 complements from the 16 donors in the HCV infection group and 151 from the healthy control group. Of the 129 analyzable sperm metaphase spreads in the HCV infection group, 14 (10.85%) complements contained chromosomal aberrations, which was significantly higher than the number (9/151, 5.96%) in the healthy control group (p < 0.01). Moreover, in the HCV infection group, chromosomes frequently showed anomalies such as stickiness, clumping, and failure to stain, which prevented their analysis. HCV infection has mutagenic effects on the chromosomes in sperm and may lead to extensive heredi-tary effects owing to genetic alterations and/or chromosomal aberrations. In addition, there is the possibility of vertical transmission of HCV via the germ line.

Analysis of Sperm DNA Fragmentation and Aneuploidy in 109 Infertile Patients: Are the Two Parameters Correlated?

Purpose: To evaluate the association between sperm DNA integrity and chromosomes aneuploidies in a considerable population of infertile patients undergoing assisted reproductive treatment (109 male) characterized by both normal and abnormal semen parameters. Methods: In 109 infertile patients with normal and abnormal semen parameters, the assessments of sperm DNA fragmentation by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) and chromosome aneuploidy by fluorescence in situ hybridization (FISH) have been performed on the same semen sample. Sperm samples were collected by masturbation into sterile cups after 3-5 days of sexual abstinence, allowed to liquefy for 30 min at room temperature and then divided in two aliquots, one processed by double gradient centrifugation (DGC) and used for TUNEL assay, whereas the remained aliquot was left unprocessed and used for FISH test. Results: The main results indicate a significant positive correlation between sperm chromosome aneuploidies and DNA integrity in patients with abnormal semen parameters (R=0.516 p=0,000) and negative not significant correlation in patients with normal seminal parameters (R=-0.105, p=0.476). Conclusions: Assuming the positive correlation between the two biomarkers in patients with defective spermatogenesis, high DNA fragmentation index (DFI) could perhaps be indicator of high chromosome aneuploidies level, thus increasing the risk of generating aneuploid embryos. Therefore, a clinical strategy could probably be to integrate also the preimplantation genetic screening (PGS) in ART treatment plan, in addition to the evaluation of sperm DNA fragmentation and/or sperm chromosome aneuploidy, to avoid transfer of chromosomally abnormal embryos.

Research on the Vertical Transmission of Hepatitis C Gene from Father-to-child via Human Sperm.

The aim was to develop a better experimental model which could facilitate further studies assessing the vertical HCV gene transmission via human spermatozoa, and verify the possibility of father-to-child transmission of the HCV gene. The recombinant plasmid pIRES2-EGFP-HCV C was constructed. Fluorescence in situ hybridization was performed to detect the integration of the HCV C gene in human sperm genome and in zygote's pronucleus. Successful construction of recombinant plasmid pIRES2-EGFP-HCV C was confirmed by restriction mapping, PCR, and sequencing. Positive HCV C DNA signals were observed in sperm heads, human sperm chromosomes and two-cell embryos in transfected samples. No positive signal was found in normal control and HCV infected groups. The recombinant plasmid pIRES2-EGFP-HCV C was successfully constructed. The HCV C gene was able to pass through the sperm membrane and integrate into the sperm genome. Human sperm carrying the HCV C gene was able to achieve normal fertilization. The replication of the sperm-mediated HCV C gene was synchronized with that of the host genome. Our results provide direct evidence for vertical transmission of the HCV C gene from father-to-child via human sperm.

Association study of telomere length with idiopathic male infertility

Telomeres are evolutionary conserved, multifunctional DNA-protein complexes located at the ends of eukaryotic chromosomes. Telomeres maintain chromosome stability and genome integrity and also play an important role in meiosis which aid in synapsis, homologous recombination, and segregation. Sperm telomere has been reported to play an important role in fertilization and embryo development. Nowadays, the association between telomere and reproduction is one of the major areas of interest, however whether sperm telomere associated with male infertility is not clear. In this study, in order to find out the association between Chinese idiopathic infertility and sperm telomere length, we analyzed the difference of sperm telomere length between idiopathic infertile men and normal fertile men, as well as the correlations between sperm telomere length and human semen characteristics. We analyzed 126 Chinese idiopathic infertile men and 138 normal fertile men for sperm telomere length by using quantitative PCR. We found that the relative sperm mean telomere length of infertile men was significantly shorter than that of fertile men (2.894 ± 0.115 vs. 4.016 ± 0.603, P=5.097 x 10⁻⁵). Both sperm count and semen progressive motility are related with telomere length. Our results suggest that sperm telomere length is associated with idiopathic male infertility of China and we proposed the possibility that shorter telomeres in sperm chromosome will reduce spermatogenesis and sperm functions, which finally affected the fertility of male.

Oxidative DNA damage in mouse sperm chromosomes: Size matters

Normal embryo and foetal development as well as the health of the progeny are mostly dependent on gamete nuclear integrity. In the present study, in order to characterize more precisely oxidative DNA damage in mouse sperm we used two mouse models that display high levels of sperm oxidative DNA damage, a common alteration encountered both in in vivo and in vitro reproduction. Immunoprecipitation of oxidized sperm DNA coupled to deep sequencing showed that mouse chromosomes may be largely affected by oxidative alterations. We show that the vulnerability of chromosomes to oxidative attack inversely correlated with their size and was not linked to their GC richness. It was neither correlated with the chromosome content in persisting nucleosomes nor associated with methylated sequences. A strong correlation was found between oxidized sequences and sequences rich in short interspersed repeat elements (SINEs). Chromosome position in the sperm nucleus as revealed by fluorescent in situ hybridization appears to be a confounder. These data map for the first time fragile mouse sperm chromosomal regions when facing oxidative damage that may challenge the repair mechanisms of the oocyte post-fertilization.