Sabine Kliesch

Sabine Kliesch
Universitätsklinikum Münster | UKM · Abteilung für Andrologie

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278
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Publications

Publications (278)
Article
Background: Recent findings demonstrate that single nucleotide variants can cause non-obstructive azoospermia (NOA). In contrast, copy number variants (CNVs) were only analysed in few studies in infertile men. Some have reported a higher prevalence of CNVs in infertile versus fertile men. Objectives: This study aimed to elucidate if CNVs are ass...
Article
Study question Can cryptozoospermic patients be sub classified based on clinical parameters? Summary answer Cryptozoospermic patients can be subdivided in two subgroups based on the histological phenotype of their testicular tissues, testicular volume and FSH levels. What is known already Cryptozoospermia is a severe form of oligozoospermia in wh...
Article
Study question In a cohort of idiopathic and unexplained infertile men we aimed to identify subgroups with similar characteristics, and therewith underlying etiologic factors, by clustering approach. Summary answer We identified two distinct patient clusters. Across all diverse phenotypes of infertility, the strongest segregation markers were FSHB...
Article
Full-text available
De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de novo mutations play an important role in severe male infertility and explain a portion of the genetic causes of this understudied disorder. To test this hypothesis, we utilize trio-based exome sequencing in a cohort of 185 inferti...
Article
Background Due to the highly variable clinical phenotype, Klinefelter Syndrome (KS) is underdiagnosed. Objective Assessment of supervised machine learning (sML)-based prediction models for identification of KS among azoospermic patients, and comparison to expert clinical evaluation. Materials and methods Retrospective patient data (karyotype, age...
Article
STUDY QUESTION Do bi-allelic variants in the genes encoding the MSH4/MSH5 heterodimer cause male infertility? SUMMARY ANSWER We detected biallelic, (likely) pathogenic variants in MSH5 (4 men) and MSH4 (3 men) in six azoospermic men, demonstrating that genetic variants in these genes are a relevant cause of male infertility. WHAT IS KNOWN ALREADY...
Article
Study question Which single nucleotide polymorphisms (SNPs) are associated with Follicle stimulating hormone (FSH) levels in men with unexplained infertility and can affect FSH action and spermatogenesis? Summary answer We identified a genomic region at chromosome 11p.14.1, including nine SNPs, that are significantly associated with FSH levels in...
Article
Study question Do DNA methylation changes occur in testicular germ cells (TGCs) from patients with impaired spermatogenesis? Summary answer TGCs from men with cryptozoospermia exhibit altered DNA methylation levels at several genomic regions, many of which are associated with genes involved in spermatogenesis. What is known already In the last 15...
Conference Paper
Study question What is the contribution of the common genetic variation to the development of unexplained male infertility due to severe spermatogenic failure (SPGF)? Summary answer Genetic polymorphisms of key immune and spermatogenesis loci are involved in the etiology of the most severe SPGF cases, defined by Sertoli cell-only (SCO) phenotype....
Article
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Study question: Do males with the rare lysosomal storage disease infantile nephropathic cystinosis (INC) have a chance of biological fatherhood? Summary answer: Cryostorage of semen could be an option for approximately 20% of young males with INC, with surgical sperm retrieval from the centre of the testes providing additional opportunities for...
Article
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Purpose Symptoms of hypogonadism are often reported by subjects with normal serum testosterone (T) levels. We aimed to assess the association between clinical symptoms in andrological outpatients and sex steroids levels. Methods This is a retrospective cross-sectional cohort study in an Academic clinic and research unit. International Index of Ere...
Article
STUDY QUESTION When should cystic fibrosis transmembrane conductance regulator (CFTR) mutation analysis be recommended in infertile men based on andrological findings? SUMMARY ANSWER CFTR mutation analysis is recommended in all men with unexplained azoospermia in the presence of normal gonadotropin levels. WHAT IS KNOWN ALREADY While 80–97% of me...
Article
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Background Scrotal colour‐Doppler ultrasound(CDUS) still suffers from lack of standardization. Hence, the European Academy of Andrology(EAA) has promoted a multicenter study to assess the CDUS characteristics of healthy‐fertile men(HFM) to obtain normative parameters. Objectives To report and discuss the scrotal organs CDUS reference ranges and ch...
Article
Azoospermia is observed in 10–15% of men suffering couple infertility. While obstructive (OA) needs to be distinguished from non-obstructive azoospermia (NOA), both entities may be due to congenital or genetically determined disorders as well as acquired disease. NOA is predominantly caused by primary testicular damage, whereas endocrine disease du...
Article
Infertility is defined as the inability of a couple to succeed in achieving a spontaneous pregnancy after 1 year. Male and female factors contribute to infertility with approximately 40% each. In the remaining cases factors that affect fertility can be found in both partners. The andrological work-up should be started simultaneously with the gyneco...
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Full-text available
Background: 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 of spermatogonial stem cells (SSCs) and/or altered functionality of testicular somatic cells (e.g. Sertoli cells, Leydig cells). Whereas sperm cryopreservation is the first-line procedure to pre...
Article
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PurposeIn males, AMH is secreted by immature Sertoli cells; following exposure to endogenous androgens, Sertoli cells undergo a process of maturation which ultimately inhibits AMH expression to undetectable levels in the serum. However, expression of AMH receptor (AMHR-2) has never been studied in human testes, and high intratubular concentrations...
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Study question: Are sequence variants in the stromal antigen 3 (STAG3) gene a cause for non-obstructive azoospermia (NOA) in infertile human males? Summary answer: Sequence variants affecting protein function of STAG3 cause male infertility due to meiotic arrest. What is known already: In both women and men, STAG3 encodes for a meiosis-specifi...
Article
For an optimal outcome in assisted reproductive treatment (ART), the preparation and selection of the appropriate sperm or sperm population is an absolute prerequisite. A wide range of different preparation methods and functional assays are available. In addition to the classical World Health Organization methods like simple washing, the swim-up te...
Article
Infertilität besteht, wenn trotz regelmäßigen, ungeschützten Geschlechtsverkehrs nach 12 Monaten keine Schwangerschaft eingetreten ist. Die Ursachen für eine ungewollte Kinderlosigkeit liegen zu etwa gleichen Teilen mit je bis zu je 40 % bei Mann und Frau. In den übrigen Fällen finden sich bei beiden Partnern Faktoren, die die Fertilität beeinträch...
Article
Eine Azoospermie findet sich bei 10–15 % der Männer, die wegen eines unerfüllten Kinderwunschs untersucht werden. Differenzialdiagnostisch sind die obstruktive (OA) und nichtobstruktive Azoospermie (NOA) zu unterscheiden, wobei jeweils kongenitale bzw. genetisch bedingte sowie erworbene Ursachen zugrunde liegen können. Am häufigsten führen primär d...
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Background: Ageing in men is believed to be associated with fertility decline and elevated risk of congenital disorders for the offspring. The previous studies also reported reduced germ and Sertoli cell numbers in older men. However, it is not clear whether ageing in men with normal spermatogenesis affects the testis and germ cell population dyna...
Article
Background The transcription factor DMRTB1 plays a pivotal role in coordinating the transition between mitosis and meiosis in murine germ cells. No reliable data are available for human testis. Objectives The present study aims to examine the testicular expression pattern of DMRTB1 in men showing normal and impaired spermatogenesis. Materials and...
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Purpose To study if short-term exposure (2 h and 6 h) of endometrial/endometriotic tissues and cells to 10% seminal plasma (SP) can induce EMT/metaplasia. Methods Basic research experimental study was carried out in a University hospital-based fertility center. Semen samples, peritoneal fluid (PF) from endometriosis patients, endometrial biopsy fr...
Article
Background Human testicular germ cell tumours (TGCT) arise from germ cell neoplasia in situ (GCNIS) cells that originate from foetal germ cell precursors. Activin A is central to normal foetal testis development, and its dysregulation may contribute to TGCT aetiology. Objective (i) To test whether the expression profiles of activin A targets in no...
Article
Full-text available
Klinefelter syndrome (KS) and undescended testes (UDT) are known etiologies for non‐obstructive azoospermia (NOA), and coexistence of both etiologies is not uncommon. Patients with both KS and a history of UDT are therefore considered to have extremely reduced chances for paternity. We aimed to analyze the impact of previous surgically corrected un...
Article
Study question: Can a systematic scoring procedure provide crucial information on the status of highly heterogeneous immature human testicular tissues in the context of cryopreservation for fertility preservation? Summary answer: We developed a systematic histological score as a novel diagnostic tool which differentiates the patient cohort accor...
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Study question: Can enzymatically dispersed testicular cells from adult men reassemble into seminiferous cord-like structures in vitro? Summary answer: Adult human testicular somatic cells reassembled into testicular cord-like structures via dynamic interactions of Sertoli and peritubular cells. What is known already: In vitro approaches using...
Article
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Testicular germ cell cancer (TGCC) is derived from germ cell neoplasia in situ (GCNIS), which arises due to niche disturbances affecting the Sertoli cells. It is believed that exogenous endocrine factors have a crucial role in governing neoplastic transformation but on a strong hereditary background. Follicle-stimulating hormone (FSH) is the major...
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Patients with gender dysphoria are offered cross-sex hormone therapy and sex reassignment surgery to achieve the transition between the sex assigned at birth and gender identity. According to international guidelines, cross-sex hormone therapy in trans-women should lead to a psychologically and physiologically healthy body with feminized serum horm...
Article
Die andrologische Diagnostik klärt durch die sorgfältige (Paar‑)Anamnese unter Berücksichtigung besonderer Risikofaktoren, einer Skrotalsonographie, einer Hormon- und Ejakulatdiagnostik Störungen der Zeugungsfähigkeit ab. Bei schweren Fertilitätsstörungen ist die genetische Differentialdiagnostik indiziert. Therapeutisch werden präventive, medikame...
Article
Although several progestins have been tested for hormonal male contraception, the effects of dosage and nature of various progestins on gonadotropin suppression combined with and without additional testosterone has not been performed in a comparative trial. The aim of this study was to evaluate the differential impact of four oral or transdermal pr...
Article
STUDY QUESTION Is the molecular profile of human spermatogonia homogeneous or heterogeneous when analysed at the single-cell level? SUMMARY ANSWER Heterogeneous expression profiles may be a key characteristic of human spermatogonia, supporting the existence of a heterogeneous stem cell population. WHAT IS KNOWN ALREADY Despite the fact that many...
Chapter
Varicocele is defined as a palpable dilated, elongated, and tortuous pampiniform plexus of veins draining the testis. The prevalence of varicocele is high with about 20% of men and increased in patients with primary infertility to 35%. The evidence-based recommendations for management of varicocele are under constant modification. There is no conse...
Chapter
Varicocele is defined as a palpable dilated, elongated, and tortuous pampiniform plexus of veins draining the testis. The prevalence of varicocele is high with about 20% of men and increased in patients with primary infertility to 35%. The evidence-based recommendations for management of varicocele are under constant modification. There is no conse...
Chapter
Introduction Spermatozoa have to be separated from seminal fluid to omit negative influences and to ensure best assisted reproductive technology (ART) results. Several preparation techniques exist that can be used to enrich the best motile and morphologically normal spermatozoa: (1) simple washing, (2) swim-up (with or without washing step) and (3)...
Article
Full-text available
Within the human testis, large amounts of sulfated steroid hormones are produced. As shown in breast tissue and placenta, these might not only be excretion intermediates, but re-activated in target cells by steroid sulfatase (STS). This process is called sulfatase pathway and may play a pivotal role in para- and/or intracrine regulation by creating...
Article
Patients with Klinefelter's syndrome experience progressive testicular degeneration resulting in impaired endocrine function and azoospermia. What proportion of adolescents develop testosterone deficiency during puberty and how many have spermatozoa in their semen is unclear to date. We aimed to investigate testicular function during puberty and yo...
Article
Much of spermatid differentiation takes place in the absence of active transcription, but in the early phase, large amounts of mRNA are synthesized, translationally repressed, and stored. Most nucleosomal histones are then degraded, and chromatin is repackaged by protamines. For both transcription and the histone-to-protamine transition in differen...
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The 'selfish spermatogonial selection'- model was proposed to explain the paternal age effect (PAE) of some congenital disorders associated with point mutations in male germ cells. According to this, spermatogonia carrying pathogenic mutations gain a selection advantage over non-mutated spermatogonia which leads to an increased number of mutated sp...
Article
Germ cell and Sertoli cell proliferation and maturation in human testes occur in three main waves, during the late fetal and early neonatal period and at early puberty. They are triggered by periods of increased activity of the hypothalamic-pituitary-gonadal (HPG) axis. In hypogonadotropic hypogonadism (HH), these processes are variably disturbed....
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Androgens play an important role for the development of male fertility and gained interest as growth and survival factors for certain types of cancer. Androgens act via the androgen receptor (AR/Ar), which is involved in various cell biological processes such as sex differentiation. To study the functional mechanisms of androgen action, cell cultur...
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Background In Germany there is an emerging trend for postponing parenthood due to non-medical, sociocultural reasons. This clearly impacts on the reproductive success due to an age-dependent decrease in fertility. Thus, strategies and techniques are currently discussed which could preserve the female fertility status, among which social freezing (c...
Article
In pre-pubertal boys ≥ 14 years, the differentiation between constitutional delay of growth and puberty (CDGP) and hypogonadotropic hypogonadism (HH) is challenging, as current diagnostic tools have limitations in sensitivity and specificity. The aim of this study was to assess the usefulness of markers of gonadal activity, growth axis activation a...
Article
Intracytoplasmic sperm injection (ICSI) using spermatozoa from patients with severe oligoasthenoteratozoospermia is still a challenge. Although spermatozoa are available, lower fertilisation rates as well as compromised pregnancy rates are observed after ICSI. We aimed at identifying respective parameters in the pre-values of ejaculate samples used...
Article
Microsurgical testicular sperm extraction (mTESE), combined with intracytoplasmic sperm injection (ICSI) represents a chance for azoospermic men with Klinefelter's syndrome (KS) to father children. The objective of this study was to identify predictive factors for the success of mTESE from adolescents and adults with KS. The clinical data of 50 lat...
Article
Sexual functional dysfunctions represent a multidimensional nosological entity. Apart from the directly measurable pathophysiological parameters, psychological and dynamic partnership aspects are almost always involved. These can exert a triggering and a potentiating influence. Similarly, sociocultural factors have to be taken into account. In men...
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To compare mechanical dissociation, employing the Medimachine system, and enzymatic digestion of human testicular tissues with respect to the proportion of spermatogonia and somatic cells, with the long-term objective of establishing human spermatogonial cultures. Experimental basic science study. Reproductive biology laboratory. Testicular tissues...
Article
Background: The genetic basis of nonobstructive azoospermia is unknown in the majority of infertile men. Methods: We performed array comparative genomic hybridization testing in blood samples obtained from 15 patients with azoospermia, and we performed mutation screening by means of direct Sanger sequencing of the testis-expressed 11 gene (TEX11...
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BACKGROUND: An appropriate normalization strategy is crucial for data analysis from real time reverse transcription polymerase chain reactions (RT-qPCR). It is widely supported to identify and validate stable reference genes, since no single biological gene is stably expressed between cell types or within cells under different conditions. Differen...
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The chemokine receptor CXCR7 interacts with the chemokines CXCL11 and CXCL12. During development, this ligand receptor system (C-X-C) provokes cell-type-specific responses in terms of migration, adhesion or ligand sequestration. It is active in zebrafish and rodents but no data are available for its presence or function in primate testes. Real-time...
Conference Paper
Introduction & Aim: According to standardized guidelines humans with GD receive cross-sex hormone therapy (CSHT) for up to 2 years before SRS. In order to assess the effectiveness of CSHT we evaluated changes of body constitution, testes and hormonal status in a multi-center study with 3 clinics advising different treatment strategies. Material & M...
Conference Paper
[15:40 – 15:50]Context: The FSHB -211G>T (rs10835638) single-nucleotide polymorphism (SNP) has previously been identified to be associated with reduced serum FSH levels and downstream reproductive parameters, e.g., sperm concentration/count, in men. Given the negative impact of the minor allele on FSH levels and spermatogenesis, T allele carriers m...
Article
Sexuelle Funktionsstörungen sind eine multidimensionale nosologische Entität. Neben direkt messbaren pathophysiologischen Parametern sind praktisch immer auch psychologische und beziehungsdynamische Aspekte beteiligt. Diese können Auslöser oder Verstärker sein. Ebenso sind sozio-kulturelle Faktoren zu beachten. Bei Männern ist die Problematik häufi...
Article
Context: Klinefelter syndrome (KS) is the most common chromosome disorder in men (47,XXY), exhibiting a phenotype with marked variation and increased morbidity. The pathophysiological link between the supernumerary X chromosome and the clinical phenotype remains unknown. Objective: To elucidate whether differential gene expression patterns can b...
Article
Full-text available
Imprinted genes are expressed either from the paternal or the maternal allele, because the other allele has been silenced in the mother's or father's germline. Imprints are characterized by DNA methylation at CpG sites. Recently, abnormal sperm parameters and male infertility have been linked to aberrant methylation patterns of imprinted genes in s...
Article
The diagnostic workflow to evaluate male infertility follows a systematic approach to elucidate previous factors influencing fertility and the present status. The medical history should be taken, preferably in the presence of the female partner, and a clinical examination focusing on testicular morphology and function is done, followed by laborator...
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Full-text available
Klinefelter syndrome (47, XXY) is the most frequent genetic cause of male infertility and individuals share the endocrine hallmark of hypergonadotropic hypogonadism. Single-nucleotide polymorphisms located within the FSHB/FSHR gene were recently shown to impact serum follicle-stimulating hormone (FSH) levels and other reproductive parameters in men...