The Impact of SARS-CoV-2 on Sperm Cryostorage, Theoretical or Real Risk?

Cryopreservation of human gametes and embryos as well as human reproductive tissues has been characterized as an essential process and aspect of assisted reproductive technology (ART). Notably, sperm cryopreservation is a fundamental aspect of cryopreservation in oncological patients or patients undergoing gonadotoxic treatment. Given that there is a risk of contamination or cross-contamination, either theoretical or real, during the procedures of cryopreservation and cryostorage, both the European Society for Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM) have provided updated guidelines for preventing or reducing the contamination risk of sexually transmitted viruses. Given the ongoing and worldwide COVID-19 pandemic, there is considerable interest in what measures should be taken to mitigate SARS-CoV-2 contamination during cryopreservation and cryostorage of semen samples. The SARS-CoV-2 virus is the virus that causes COVID-19, and whose transmission and infection is mainly aerosol-mediated. Several ART professional societies, including ESHRE and ASRM have proposed measures to mitigate the spread of the SARS-CoV-2 virus. Whether the proposed safety directives are enough to mitigate the possible SARS-CoV-2-contamination of sperm samples during cryopreservation or whether the policies should be re-evaluated will be discussed in this review. Additionally, insights regarding the possible impact of COVID-19 vaccination on the safety of sperm cryopreservation will be discussed

Chromosomal disorders and male infertility

Infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family. Despite this, the molecular and genetic factors underlying the cause of infertility remain largely undiscovered. Nevertheless, more and more genetic factors associated with infertility are being identified. This review will focus on our current understanding of the chromosomal basis of male infertility specifically: chromosomal aneuploidy, structural and numerical karyotype abnormalities and Y chromosomal microdeletions. Chromosomal aneuploidy is the leading cause of pregnancy loss and developmental disabilities in humans. Aneuploidy is predominantly maternal in origin, but concerns have been raised regarding the safety of intracytoplasmic sperm injection as infertile men have significantly higher levels of sperm aneuploidy compared to their fertile counterparts. Males with numerical or structural karyotype abnormalities are also at an increased risk of producing aneuploid sperm. Our current understanding of how sperm aneuploidy translates to embryo aneuploidy will be reviewed, as well as the application of preimplantation genetic diagnosis (PGD) in such cases. Clinical recommendations where possible will be made, as well as discussion of the use of emerging array technology in PGD and its potential applications in male infertility

Human Sperm Chromosomes: To Form Hairpin-Loops, Or Not to Form Hairpin-Loops, That Is the Question

Background: Genomes are non-randomly organized within the interphase nucleus; and spermatozoa are proposed to have a unique hairpin-loop configuration, which has been hypothesized to be critical for the ordered exodus of the paternal genome following fertilization. Recent studies suggest that the hairpin-loop model of sperm chromatin organization is more segmentally organized. The purpose of this study is to examine the 3D organization and hairpin-loop configurations of chromosomes in human spermatozoa. Methods: Three-color sperm-fluorescence in-situ hybridization was utilized against the centromeres, and chromosome p- and q-arms of eight chromosomes from five normozoospermic donors. Wide-field fluorescence microscopy and 3D modelling established the radial organization and hairpin-loop chromosome configurations in spermatozoa. Results: All chromosomes possessed reproducible non-random radial organization (p \u3c 0.05) and formed discrete hairpin-loop configurations. However, chromosomes preferentially formed narrow or wide hairpin-loops. We did not find evidence to support the existence of a centralized chromocenter(s) with centromeres being more peripherally localized than one or both of their respective chromosome arms. Conclusion: This provides further evidence to support a more segmental organization of chromatin in the human sperm nucleus. This may be of significance for fertilization and early embryogenesis as specific genomic regions are likely to be exposed, remodeled, and activated first, following fertilization

A new model of sperm nuclear architecture following assessment of the organization of centromeres and telomeres in three-dimensions

The organization of chromosomes in sperm nuclei has been proposed to possess a unique “hairpin-loop” arrangement, which is hypothesized to aid in the ordered exodus of the paternal genome following fertilization. This study simultaneously assessed the 3D and 2D radial and longitudinal organization of telomeres, centromeres, and investigated whether chromosomes formed the same centromere clusters in sperm cells. Reproducible radial and longitudinal non-random organization was observed for all investigated loci using both 3D and 2D approaches in multiple subjects. We report novel findings, with telomeres and centromeres being localized throughout the nucleus but demonstrating roughly a 1:1 distribution in the nuclear periphery and the intermediate regions with \u3c15% occupying the nuclear interior. Telomeres and centromeres were observed to aggregate in sperm nuclei, forming an average of 20 and 7 clusters, respectively. Reproducible longitudinal organization demonstrated preferential localization of telomeres and centromeres in the mid region of the sperm cell. Preliminary evidence is also provided to support the hypothesis that specific chromosomes preferentially form the same centromere clusters. The more segmental distribution of telomeres and centromeres as described in this study could more readily accommodate and facilitate the sequential exodus of paternal chromosomes following fertilization

Meiotic recombination and male infertility: from basic science to clinical reality?

Infertility is a common problem that affects approximately 15% of the population. Although many advances have been made in the treatment of infertility, the molecular and genetic causes of male infertility remain largely elusive. This review will present a summary of our current knowledge on the genetic origin of male infertility and the key events of male meiosis. It focuses on chromosome synapsis and meiotic recombination and the problems that arise when errors in these processes occur, specifically meiotic arrest and chromosome aneuploidy, the leading cause of pregnancy loss in humans. In addition, meiosis-specific candidate genes will be discussed, including a discussion on why we have been largely unsuccessful at identifying disease-causing mutations in infertile men. Finally clinical applications of sperm aneuploidy screening will be touched upon along with future prospective clinical tests to better characterize male infertility in a move towards personalized medicine

Chromosome territory repositioning induced by PHA-activation of lymphocytes: A 2D and 3D appraisal

BACKGROUND: Genomes and by extension chromosome territories (CTs) in a variety of organisms exhibit nonrandom organization within interphase nuclei. CTs are susceptible to movement upon induction by a variety of stimuli, including: cell differentiation, growth factors, genotoxic agents, proliferating status, and stimulants that induce novel transcription profiles. These findings suggest nuclear architecture can undergo reorganization, providing support for a functional significance of CT organization. The effect of the initiation of transcription on global scale chromatin architecture has been underexplored. This study investigates the organization of all 24 human chromosomes in lymphocytes from two individuals in resting and phytohaemagglutinin activated lymphocytes using 2D and 3D approaches. RESULTS: The radial organization of CTs in lymphocytes in both resting and activated lymphocytes follows a gene-density pattern. However, CT organization in activated nuclei appears less constrained exhibiting a more random organization. We report differences in the spatial relationship between homologous and heterologous CTs in activated nuclei. In addition, a reproducible radial hierarchy of CTs was identified and evidence of a CT repositioning was observed in activated nuclei using both 2D and 3D approaches. CONCLUSIONS: Alterations between resting and activated lymphocytes could be adaptation of CTs to the new transcription profile and possibly the formation of new neighborhoods of interest or interaction of CTs with nuclear landmarks. The increased distances between homologous and heterologous CTs in activated lymphocytes could be a reflection of a defensive mechanism to reduce potential interaction to prevent any structural chromosome abnormalities (e.g. translocations) as a result of DNA damage that increases during lymphocyte activation

The impact of sars-cov-2 on sperm cryostorage, theoretical or real risk?

Cryopreservation of human gametes and embryos as well as human reproductive tissues has been characterized as an essential process and aspect of assisted reproductive technology (ART). Notably, sperm cryopreservation is a fundamental aspect of cryopreservation in oncological patients or patients undergoing gonadotoxic treatment. Given that there is a risk of contamination or cross-contamination, either theoretical or real, during the procedures of cryopreservation and cryostorage, both the European Society for Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM) have provided updated guidelines for preventing or reducing the contamination risk of sexually transmitted viruses. Given the ongoing and worldwide COVID-19 pandemic, there is considerable interest in what measures should be taken to mitigate SARS-CoV-2 contamination during cryopreservation and cryostorage of semen samples. The SARS-CoV-2 virus is the virus that causes COVID-19, and whose transmission and infection is mainly aerosol-mediated. Several ART professional societies, including ESHRE and ASRM have proposed measures to mitigate the spread of the SARS-CoV-2 virus. Whether the proposed safety directives are enough to mitigate the possible SARS-CoV-2-contamination of sperm samples during cryopreservation or whether the policies should be re-evaluated will be discussed in this review. Additionally, insights regarding the possible impact of COVID-19 vaccination on the safety of sperm cryopreservation will be discussed

Erratum: Corrigendum: Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution

International Chicken Genome Sequencing Consortium. The Original Article was published on 09 December 2004. Nature432, 695–716 (2004). In Table 5 of this Article, the last four values listed in the ‘Copy number’ column were incorrect. These should be: LTR elements, 30,000; DNA transposons, 20,000; simple repeats, 140,000; and satellites, 4,000. These errors do not affect any of the conclusions in our paper. Additional information. The online version of the original article can be found at 10.1038/nature0315

Human Sperm Chromosomes: To Form Hairpin-Loops, Or Not to Form Hairpin-Loops, That Is the Question

Background: Genomes are non-randomly organized within the interphase nucleus; and spermatozoa are proposed to have a unique hairpin-loop configuration, which has been hypothesized to be critical for the ordered exodus of the paternal genome following fertilization. Recent studies suggest that the hairpin-loop model of sperm chromatin organization is more segmentally organized. The purpose of this study is to examine the 3D organization and hairpin-loop configurations of chromosomes in human spermatozoa. Methods: Three-color sperm-fluorescence in-situ hybridization was utilized against the centromeres, and chromosome p- and q-arms of eight chromosomes from five normozoospermic donors. Wide-field fluorescence microscopy and 3D modelling established the radial organization and hairpin-loop chromosome configurations in spermatozoa. Results: All chromosomes possessed reproducible non-random radial organization (p < 0.05) and formed discrete hairpin-loop configurations. However, chromosomes preferentially formed narrow or wide hairpin-loops. We did not find evidence to support the existence of a centralized chromocenter(s) with centromeres being more peripherally localized than one or both of their respective chromosome arms. Conclusion: This provides further evidence to support a more segmental organization of chromatin in the human sperm nucleus. This may be of significance for fertilization and early embryogenesis as specific genomic regions are likely to be exposed, remodeled, and activated first, following fertilization