A5065771641- Sperm and Testicular Function
- Reproductive Biology and Fertility
- Sexual Differentiation and Disorders
- Renal and related cancers
- Reproductive Health and Technologies
- Epigenetics and DNA Methylation
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Prenatal Screening and Diagnostics
- LGBTQ Health, Identity, and Policy
- Pluripotent Stem Cells Research
- Testicular diseases and treatments
- RNA Interference and Gene Delivery
- Genetic Syndromes and Imprinting
- Immunotherapy and Immune Responses
- Genomics and Chromatin Dynamics
- Chemokine receptors and signaling
- Ovarian function and disorders
- scientometrics and bibliometrics research
- Chromosomal and Genetic Variations
- Molecular Biology Techniques and Applications
- Biomedical Text Mining and Ontologies
- Reproductive System and Pregnancy
- Sex and Gender in Healthcare
- Sexual function and dysfunction studies
- RNA modifications and cancer
University of Münster
2015-2024
University Hospital Münster
2015-2024
Reproduktionsmedizin München
2020-2023
Infertility is an important side effect of treatments used for cancer and other non-malignant conditions in males. This may be due to the loss spermatogonial stem cells (SSCs) and/or altered functionality testicular somatic (e.g. Sertoli cells, Leydig cells). Whereas sperm cryopreservation first-line procedure preserve fertility post-pubertal males, this option does not exist prepubertal boys. For patients unable produce at high risk losing their fertility, tissue freezing now proposed as...
Abstract STUDY QUESTION Twenty years after the inception of first fertility preservation programme for pre-pubertal boys, what are current international practices with regard to cryopreservation immature testicular tissue? SUMMARY ANSWER Worldwide, tissue has been cryopreserved from over 3000 boys under age 18 a variety malignant and non-malignant indications; there is variability in related eligibility, clinical assessment, storage, funding. WHAT IS KNOWN ALREADY For male patients receiving...
Male infertility affects ∼7% of men, but its causes remain poorly understood. The most severe form is non-obstructive azoospermia (NOA), which is, in part, caused by an arrest at meiosis. So far, only a few validated disease-associated genes have been reported. To address this gap, we performed whole-exome sequencing 58 men with unexplained meiotic and identified the same homozygous frameshift variant c.676dup (p.Trp226LeufsTer4) M1AP, encoding meiosis 1 associated protein, three unrelated...
Despite the high incidence of male infertility, only 30% infertile men receive a causative diagnosis. To explore regulatory mechanisms governing human germ cell function in normal and impaired spermatogenesis (crypto), we performed single-cell RNA sequencing (>30,000 cells). We find major alterations crypto spermatogonial compartment with increased numbers most undifferentiated spermatogonia (PIWIL4+). also observe transcriptional switch within driven by prolonged expression transcription...
Abstract Non-obstructive azoospermia, the absence of sperm in ejaculate due to disturbed spermatogenesis, represents most severe form male infertility. De novo microdeletions Y-chromosomal AZFa region are one few well-established genetic causes for NOA and routinely analysed diagnostic workup affected men. So far, it is unclear which three genes located chromosomal indispensible germ cell maturation. Here we present four different likely pathogenic loss-of-function variants gene DDX3Y...
Sperm production and function require the correct establishment of DNA methylation patterns in germline. Here, we examined genome-wide changes during human spermatogenesis its alterations disturbed spermatogenesis. We found that is associated with remodeling methylome, comprising a global decline primary spermatocytes followed by selective remethylation, resulting spermatids/sperm-specific methylome. Hypomethylated regions spermatids/sperm were enriched specific transcription factor binding...
piRNAs are crucial for transposon silencing, germ cell maturation, and fertility in male mice. Here, we report on the genetic landscape of piRNA dysfunction humans present 39 infertile men carrying biallelic variants 14 different pathway genes, including PIWIL1, GTSF1, GPAT2, MAEL, TDRD1, DDX4. In some affected men, testicular phenotypes differ from those respective knockout mice range complete loss to production a few morphologically abnormal sperm. A reduced number pachytene was detected...
Abstract Homologous recombination rearranges genetic information during meiosis to generate new combinations of variants. Recombination also causes mutations, affects the GC content genome and reduces selective interference. Here, we use HiFi long-read sequencing directly detect crossover gene conversion events from switches between two haplotypes along single HiFi-reads testis tissue humans, chimpanzees gorillas as well human sperm samples. Furthermore, based on DNA methylation calls,...
Is the molecular profile of human spermatogonia homogeneous or heterogeneous when analysed at single-cell level? Heterogeneous expression profiles may be a key characteristic spermatogonia, supporting existence stem cell population. Despite fact that many studies have sought to identify specific markers for fingerprint these cells remains hitherto unknown. Testicular tissues from patients with spermatogonial arrest (arrest, n = 1) and qualitatively normal spermatogenesis (normal, 7) were...
The most common sex chromosomal aneuploidy in males is Klinefelter syndrome, which characterized by at least one supernumerary X chromosome. While these men have long been considered infertile, focal spermatogenesis can be observed some patients, and sperm surgically retrieved used for artificial reproductive techniques. Although gametes fertility treatments, little known about the molecular biology of germline men. Specifically, it unclear if germ cells syndrome correctly establish...
Can a systematic scoring procedure provide crucial information on the status of highly heterogeneous immature human testicular tissues in context cryopreservation for fertility preservation? We developed histological score as novel diagnostic tool which differentiates patient cohort according to germ cell differentiation and number spermatogonia (normal, diminished absent), could be relevant clinic. Cryopreservation tissue boys is currently considered option future restoration. However,...
Abstract Background In the past 15 years, numerous studies have described aberrant DNA methylation of imprinted genes (e.g. MEST and H19 ) in sperm oligozoospermic men, but prevalence genomic extent abnormal patterns remained unknown. Results Using deep bisulfite sequencing (DBS), we screened swim-up samples from 40 normozoospermic 93 patients diagnosed as oligoasthenoteratozoospermic, oligoteratozoospermic or oligozoospermic, which are termed OATs throughout manuscript, for methylation....
Mutations affecting the germline can result in infertility or generation of germ cell tumors (GCT), highlighting need to identify and characterize genes controlling development. The RNA-binding protein E3 ubiquitin ligase TRIM71 is essential for embryogenesis, its expression has been reported GCT adult mouse testes. To investigate role mammalian embryonic development, we generated a germline-specific conditional Trim71 knockout (cKO) using early primordial (PGC) marker Nanos3 as...
Abstract Male infertility has been linked to M1AP. In mice, M1AP interacts with the ZZS proteins SHOC1/TEX11/SPO16, promoting DNA class I crossover formation during meiosis. To determine whether and are involved in human male by recombination failure, we screened for biallelic/hemizygous loss-of-function (LoF) variants genes select men presumed protein deficiency ( N = 24). After in-depth characterisation of testicular phenotypes, identified gene-specific meiotic impairments: shared an early...
The timing of de novo DNA methylation in male germ cells during human testicular development is yet unsolved. Apart from that, the stability established imprinting patterns vitro controversially discussed. This study aimed at determining and assessing status vitro. We employed marmoset monkey (Callithrix jacchus) as it considered best non-human primate model for development. selected neonatal, pre-pubertal, pubertal, adult animals (n = 3, each) assessed cell global levels by 5-methyl...
Does irradiation evoke adverse effects in germ and somatic cells testis xenografts from prepubertal monkeys?In addition to the expected depletion of cells, a dose-dependent effect was observed at mRNA protein level Sertoli peritubular myoid cells.Testicular studies monkeys have focused on cells. Previous using intact animals or reported that are highly sensitive irradiation. Their demonstrated by morphometric histological analyses. The expression cell markers, however, has not yet been...
In mice the chemokine Cxcl12 and its receptor Cxcr4 participate in maintenance of spermatogonial population during postnatal development. More complexity arises since also binds to non-classical/atypical Cxcr7. We explored expression pattern Cxcl12, Cxcr7 development mouse testes investigated response Cxcr4, SSC-niche associated factors busulfan-induced germ cell depletion subsequent recovery by RNA analysis localization proteins. neonatal transcript levels were relatively low protein was...
Abstract Background Several studies have reported an association between male infertility and aberrant sperm DNA methylation patterns, in particular imprinted genes. In a recent investigation based on whole methylome deep bisulfite sequencing, we not found any evidence for such association, but demonstrated that somatic contamination genetic variation confound of severely oligozoospermic men. To find out whether testicular germ cells (TGCs) patients might carry methylation, compared the TGC...