Sperm chromatin structure assay (SCSA®) and flow cytometry-assisted TUNEL assay provide a concordant assessment of sperm DNA fragmentation as a function of age in a large cohort of approximately 10,000 patients DOI Creative Commons

Paria Behdarvandian,

Ali Nasr-Esfahani, Marziyeh Tavalaee

и другие.

Basic and Clinical Andrology, Год журнала: 2023, Номер 33(1)

Опубликована: Ноя. 30, 2023

Sperm DNA integrity is increasingly seen as a critical characteristic determining reproductive success, both in natural reproduction and assisted technologies (ART). Despite this awareness, sperm nuclear tests are still not part of routine examinations for either infertile men or fertile wishing to assess their capacity. This due the unavailability tests. On contrary, several relevant but distinct available have been used many clinical trials, which has led conflicting results confusion. The reasons mainly lack standardization between different clinics themselves. In addition, small number samples analyzed these trials often weakened value analyses performed. present work, we large cohort semen samples, covering wide age range, were simultaneously evaluated fragmentation (SDF) using two most frequently SDF assays, namely TUNEL assay chromatin structure (SCSA®). At same time, standard seminal parameters (sperm motility, morphology, count) correlations age, conventional analyzed.We show that SCSA® assessments produce concordant data. However, assessed by systematically lower than SCSA®. Regardless test used, increases steadily during aging, while HDS parameter (High stainability via SCSA®) remains unchanged. analyzed, do seem discriminate with aging. Only volume motility significantly oldest group [50-59 years age].In an age-dependent parameter, increasing linearly assessment flow cytometry-assisted well correlated, although less sensitive difference sensitivity should be taken into account final true level nucleus given sample. classical (motility, change dramatically making them inadequate fertility potential individual.RéSUMé: CONTEXTE: l'intégrité de l'ADN des spermatozoïdes est plus en considérée comme une caractéristique essentielle déterminant le succès la reproduction, tant dans naturelle que les techniques assistée (AMP). Malgré cette prise conscience, d'intégrité nucléaire ne font toujours pas partie examens pour hommes infertiles ou fertiles souhaitant évaluer leur capacité reproduction. Cette situation n'est à l'indisponibilité Au contraire, plusieurs pertinents mais distincts sont disponibles et ont été utilisés nombreux essais cliniques, ce qui donné lieu résultats contradictoires certaine Les raisons principalement manque normalisation entre différentes cliniques eux-mêmes. En outre, petit nombre d'échantillons analysés ces souvent affaibli valeur effectuées. Dans présent travail, nous avons utilisé vaste cohorte d'échantillons, couvrant tranche d'âge, évalués simultanément l'aide deux fréquemment utilisés, savoir chromatine Parallèlement, paramètres séminaux (motilité, morphologie, numération) étaient échantillons, corrélations l'âge, niveau conventionnels analysées. RéSULTATS: Nous montrons évaluations produisent données concordantes. Cependant, évalué par systématiquement faible celui Quel soit utilisé, augmente régulièrement au cours du vieillissement, alors paramètre (« High stainability» reste inchangé. analysée, spermatiques semblent varier avec vieillissement. Seuls mobilité significativement faibles groupe d'âge élevé analysé [50–59 ans]. CONCLUSIONS: grande spermatique un dépendant augmentant linéairement L'évaluation l'évaluation cytométrie flux bien corrélées, moins sensible différence sensibilité doit être compte finale réel noyau d'un échantillon donné. classiques sperme spermatozoïdes) changent façon spectaculaire rend inadéquats potentiel fertilité individu.

De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome DOI Creative Commons
Yuyang Chen, Ruebena Dawes, Hyung Chul Kim

и другие.

Nature, Год журнала: 2024, Номер 632(8026), С. 832 - 840

Опубликована: Июль 11, 2024

Abstract Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily protein-coding genes 1 . Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify RNA RNU4-2 as a syndromic NDD gene. encodes U4 small nuclear (snRNA), which is critical component U4/U6.U5 tri-snRNP complex major spliceosome 2 We an 18 base pair region mapping two structural elements U4/U6 snRNA duplex (the T-loop and stem III) that severely depleted variation general population, but heterozygous variants 115 NDD. Most (77.4%) have same highly recurrent single insertion (n.64_65insT). In 54 whom it could be determined, de novo were all on maternal allele. demonstrate expressed developing human brain, contrast RNU4-1 other homologues. Using sequencing, show how 5′ splice-site use systematically disrupted variants, consistent known role this during activation. Finally, estimate explain 0.4% This work underscores importance rare will provide diagnosis thousands worldwide.

Язык: Английский

Процитировано

28

Transgenerational effects of paternal exposures: the role of germline de novo mutations DOI Open Access
Hojat Dehghanbanadaki, Masaya Jimbo, Kiarad Fendereski

и другие.

Andrology, Год журнала: 2024, Номер unknown

Опубликована: Фев. 23, 2024

Abstract Germline de novo mutations (DNMs) refer to spontaneous arising during gametogenesis, resulting in genetic changes within germ cells that are subsequently transmitted the next generation. While impact of maternal exposures on germline DNMs has been extensively studied, more recent studies have begun highlight increasing importance effects paternal factors. In this review, we summarized existing literature how various experienced by fathers affect DNM burden their spermatozoa, as well consequences for semen analysis parameters, pregnancy outcomes, and offspring health. A growing body supports conclusion advanced age (APA) correlates with a higher rate offspring. Furthermore, lifestyle choices, environmental toxins, assisted reproductive techniques (ART), chemotherapy associated accumulation deleterious outcomes Ultimately, our review highlights clear mode inheritance, current understanding is affected addition, explore conflicting reports or gaps knowledge should be addressed future research.

Язык: Английский

Процитировано

4

Adult Human, but Not Rodent, Spermatogonial Stem Cells Retain States with a Foetal-like Signature DOI Creative Commons
Stephen J. Bush, Rafail Nikola, Seungmin Han

и другие.

Cells, Год журнала: 2024, Номер 13(9), С. 742 - 742

Опубликована: Апрель 24, 2024

Spermatogenesis involves a complex process of cellular differentiation maintained by spermatogonial stem cells (SSCs). Being critical to male reproduction, it is generally assumed that spermatogenesis starts and ends in equivalent transcriptional states related species. Based on single-cell gene expression profiling, has been proposed undifferentiated human spermatogonia can be subclassified into four heterogenous subtypes, termed 0, 0A, 0B, 1. To increase the resolution compartment trace origin spermatogenic trajectory, we re-analysed (sc) RNA-sequencing libraries 34 post-pubescent testes generate an integrated atlas germ cell differentiation. We then used this perform comparative analyses putative SSC transcriptome both across development (using 28 foetal pre-pubertal scRNA-seq libraries) species (including data from sheep, pig, buffalo, rhesus cynomolgus macaque, rat, mouse). Alongside its detailed characterisation, show heterogeneity varies not only between but development. Our findings associate ‘state 0B’ with suppressive transcriptomic programme that, adult humans, acts functionally oppose proliferation maintain ready-to-react state. Consistent conclusion, cells—which are mitotically arrested—can characterised solely as state 0B. While 0B signature also present mice (and likely conserved at stage throughout mammals), they adulthood. conjecture rodents, foetal-like differentiates birth renewing population, whereas humans reserve supporting testicular homeostasis over longer reproductive lifespan while reducing mutagenic load. Together, these results suggest SSCs adopt differing evolutionary strategies ensure fertility genome integrity vastly life histories timeframes.

Язык: Английский

Процитировано

4

SMAD4 mutations causing Myhre syndrome are under positive selection in the male germline DOI Creative Commons
K Wood,

R. Spencer Tong,

Marialetizia Motta

и другие.

The American Journal of Human Genetics, Год журнала: 2024, Номер 111(9), С. 1953 - 1969

Опубликована: Авг. 7, 2024

Язык: Английский

Процитировано

4

Prenatal gene editing for neurodevelopmental diseases: Ethical considerations DOI Creative Commons
Rami Major, Eric T. Juengst

The American Journal of Human Genetics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0

The Executive Functioning of the Chief Executive DOI

Steven C. Hertler,

Aurelio José Figueredo, Mateo Peñaherrera‐Aguirre

и другие.

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0

Arousal, Attention, and Executive Functioning DOI

Steven C. Hertler,

Aurelio José Figueredo, Mateo Peñaherrera‐Aguirre

и другие.

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0

Global Decline in General Intelligence DOI

Steven C. Hertler,

Aurelio José Figueredo, Mateo Peñaherrera‐Aguirre

и другие.

Опубликована: Янв. 1, 2025

Процитировано

0

Toward a Consolidated Understanding of Intelligence DOI

Steven C. Hertler,

Aurelio José Figueredo, Mateo Peñaherrera‐Aguirre

и другие.

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0

The Demands of Office DOI

Steven C. Hertler,

Aurelio José Figueredo, Mateo Peñaherrera‐Aguirre

и другие.

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0