Sperm chromatin condensation and single‐ and double‐stranded DNA damage as important parameters to define male factor related recurrent miscarriage

Ribas-Maynou, Jordi; Abad, Carlos; Garcia-Segura, Sergio; Oliver-Bonet, María; Prada, Elena; Amengual, M. J.; Navarro, J.; Benet, Jordi

doi:10.1002/mrd.23424

Cited by 10 publications

(4 citation statements)

References 40 publications

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“…On the other hand, the accumulation of CNVs/LOHs in ART-aborted fetuses might be just a parallel result but not a direct reason of the abortion. Evidences had shown that DNA damage in either oocytes [26][27][28][29] or sperms [30][31][32][33] could induce spontaneous abortion. So DNA damage can be the source of both CNVs/LOHs and abortion.…”

Section: Plos Onementioning

confidence: 99%

Chromosomal variants accumulate in genomes of the spontaneous aborted fetuses revealed by chromosomal microarray analysis

Chen²,

Wang³

et al. 2021

PLoS ONE

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Spontaneous abortion is an impeding factor for the success rates of human assistant reproductive technology (ART). Causes of spontaneous abortion include not only the pregnant mothers’ health conditions and lifestyle habits, but also the fetal development potential. Evidences had shown that fetal chromosome aneuploidy is associated with fetal spontaneous abortion, however, it is still not definite that whether other genome variants, like copy number variations (CNVs) or loss of heterozygosity (LOHs) is associated with the spontaneous abortion. To assess the relationship between the fetal genome variants and abortion during ART, a chromosomal microarray data including chromosomal information of 184 spontaneous aborted fetuses, 147 adult female patients and 78 adult male patients during ART were collected. We firstly analyzed the relationship of fetal aneuploidy with maternal ages and then compared the numbers and lengths of CNVs (< 4Mbp) and LOHs among adults and aborted fetuses. In addition to the already known association between chromosomal aneuploidy and maternal ages, from the chromosomal microarray data we found that the numbers and the accumulated lengths of short CNVs and LOHs in the aborted fetuses were significantly larger or longer than those in adults. Our findings indicated that the increased numbers and accumulated lengths of CNVs or LOHs might be associated with the spontaneous abortion during ART.

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Section: Plos Onementioning

confidence: 99%

Chromosomal variants accumulate in genomes of the spontaneous aborted fetuses revealed by chromosomal microarray analysis

Chen²,

Wang³

et al. 2021

PLoS ONE

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“…Accordingly, our results evidenced lower chromatin condensation in viable than in non-viable sperm. However, while no study in the literature has simultaneously evaluated sperm viability and chromatin condensation, one could reasonably surmise that chromatin decondensation is higher in non-viable sperm due to their increased oxidative stress, as free radicals and DNA fragmentation were previously found to be positively correlated with sperm chromatin decondensation [ 15 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, many authors suggested the association of sperm DNA integrity with sperm quality and fertility in farm animals [9][10][11]. While sperm DNA integrity, assessed through different methods, is the most common genetic parameter used to predict male infertility in humans [8,12,13], different studies showed that sperm protamine content and protamine1/protamine2 ratio may also underlie infertility [14][15][16]. Although chromatin might also be contributing to fertilization success in livestock, given the relevance of nucleoprotein structure integrity [17][18][19], it has not been well-studied as a fertility biomarker [9].…”

Section: Introductionmentioning

confidence: 99%

Sperm chromatin condensation as an in vivo fertility biomarker in bulls: a flow cytometry approach

Llavanera

Ribas-Maynou

Delgado-Bermúdez

et al. 2021

J Animal Sci Biotechnol

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Background Genetic selection in cattle has been directed to increase milk production. This, coupled to the fact that the vast majority of bovine artificial inseminations (AI) are performed using cryopreserved sperm, have led to a reduction of fertility rates over the years. Thus, seeking sensitive and specific sperm biomarkers able to predict fertility rates is of vital importance to improve cattle reproductive efficiency. In humans, sperm chromatin condensation evaluated through chromomycin A3 (CMA3) has recently been purported to be a powerful biomarker for sperm functional status and male infertility. The objectives of the present study were: a) to set up a flow cytometry method for simultaneously evaluating chromatin condensation and sperm viability, and b) to test whether this parameter could be used as a predictor of in vivo fertility in bulls. The study included pools of three independent cryopreserved ejaculates per bull from 25 Holstein males. Reproductive outcomes of each sire were determined by non-return rates, which were used to classify bulls into two groups (highly fertile and subfertile). Results Chromatin condensation status of bovine sperm was evaluated through the combination of CMA3 and Yo-Pro-1 staining and flow cytometry. Sperm quality parameters (morphology, viability, total and progressive motility) were also assessed. Pearson correlation coefficients and ROC curves were calculated to assess their capacity to predict in vivo fertility. Sperm morphology, viability and total motility presented an area under the ROC curve (AUC) of 0.54, 0.64 and 0.68, respectively (P > 0.05), and thus were not able to discriminate between fertile and subfertile individuals. Alternatively, while the percentage of progressively motile sperm showed a significant predictive value, with an AUC of 0.73 (P = 0.05), CMA3/Yo-Pro-1 staining even depicted superior results for the prediction of in vivo fertility in bulls. Specifically, the percentage of viable sperm with poor chromatin condensation showed better accuracy and precision to predict in vivo fertility, with an AUC of 0.78 (P = 0.02). Conclusions Chromatin condensation evaluated through CMA3/Yo-Pro-1 and flow cytometry is defined here as a more powerful tool than conventional sperm parameters to predict bull in vivo fertility, with a potential ability to maximising the efficiency of dairy breeding industry.

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“…The vacuoles were first described as nuclear craters or thumbprints, or DNA-free areas, in connection with no or low condensation of the sperm chromatin [ 29 , 31 , 34 , 35 , 36 ]. Hence, deselecting sperm with chromatin condensation abnormalities could improve pregnancy rates and decrease miscarriage rates [ 33 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ].…”

Section: Introductionmentioning

confidence: 99%

Human Sperm Morphology as a Marker of Its Nuclear Quality and Epigenetic Pattern

Bendayan

Caceres

Saïs

et al. 2022

Cells

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Background: Human sperm chromatin condensation is a sum of epigenetic events that allows for the near-complete replacement of histones with protamines. Under high-magnification microscopy, nuclear vacuoles have been described as thumbprints with poor chromatin condensation. The objective of this study is to examine whether vacuolated spermatozoa carry specific epigenetic marks, which may influence embryo development. Methods: The presence and three-dimensional distribution of ten epigenetic marks (protamine-P2, histone-H3, H3K4me1/me2/me3, H3K9me1/me2/me3, H3K27me3, H4k20me2) were evaluated and compared in morphometrically normal spermatozoa according to the presence or absence of a large vacuole occupying more than 15% of the head surface (n = 4193). Results: Vacuolated spermatozoa were significantly more frequently labelled with H3 and H3K4me3 than normal spermatozoa (88.1% ± 2.7 and 78.5% ± 5.2 vs. 74.8% ± 4.8 and 49.1% ± 7.4, respectively; p = 0.009 and p < 0.001) and significantly less marked by P2 and H3K27me3 (50.2% ± 6.2 and 63.9% ± 6.3 vs. 82.1% ± 4.4 and 73.6% ± 5.1, respectively; p < 0.001 and p = 0.028). In three dimensions, vacuoles are nuclear concavities filled with DNA carrying the H3K4me3 marker. Conclusion: High-magnification microscopy is a simple tool to estimate in real time the sperm epigenetic profile. The selection of normal spermatozoa without vacuoles and the deselection of spermatozoa with vacuoles appear to be epigenetically favorable to embryo development and safe offspring.

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Sperm chromatin condensation and single‐ and double‐stranded DNA damage as important parameters to define male factor related recurrent miscarriage

Cited by 10 publications

References 40 publications

Chromosomal variants accumulate in genomes of the spontaneous aborted fetuses revealed by chromosomal microarray analysis

Chromosomal variants accumulate in genomes of the spontaneous aborted fetuses revealed by chromosomal microarray analysis

Sperm chromatin condensation as an in vivo fertility biomarker in bulls: a flow cytometry approach

Human Sperm Morphology as a Marker of Its Nuclear Quality and Epigenetic Pattern

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