Joachim Wistuba

Joachim Wistuba
University of Münster | WWU · Center of Reproductive Medicine and Andrology

About

179
Publications
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Introduction
As zoologist my primary scientific interests always covered evolutionary processes and mechanisms of reproduction. In an applied way, these topics are also important for fertility and infertility, thus my research at the centre is dealing with preclinical and clinical as well as basic experimental approaches, trying to link both fields to each other. My research on sex chromosomal aberrations, on male reproductive ageing and male in vitro germ cell maturation might serve as an example for this.

Publications

Publications (179)
Article
Study question What are the specific changes under gender affirming hormone therapy (GAHT) in the spermatogonial cell compartment in testicular tissues of transwomen? Summary answer GAHT has a negative effect on the most undifferentiated PIWIL4+ spermatogonia potentially leading to reduced chances for fertility preservation in transwomen. What is...
Article
Full-text available
STUDY QUESTION Are there subgroups among patients with cryptozoospermia pointing to distinct etiologies? SUMMARY ANSWER We reveal two distinct subgroups of cryptozoospermic (Crypto) patients based on testicular tissue composition, testicular volume, and FSH levels. WHAT IS KNOWN ALREADY Cryptozoospermic patients present with a sperm concentration...
Chapter
The male gonads, the testes, fulfill two essential functions. They are the site of spermatogenesis. The male gametes, the sperm, are produced here. As important is their second function as an endocrine gland that synthesizes androgens. Androgens are necessary for the formation of the typical male phenotype. The male gonad develops during the embryo...
Chapter
Successful fertilization of an egg is the ultimate goal of a mature sperm. For this process to occur correctly in vivo, the natural fertilization process follows a time- and location-dependent sequence of complex steps, beginning with production in the testis, maturation in the epididymis, and finally the fertilization of the egg. Specific proteins...
Article
In brief: Minipuberty is a transient activity period of the hypothalamic-pituitary-gonadal axis in the postnatal and infant period including surging serum concentrations of reproductive hormones. Increasing evidence points to an important role of this period for maturation of the testes and thereby for male reproductive function. Abstract: Minip...
Article
The spermatogonial compartment maintains spermatogenesis throughout the reproductive lifespan. Single-cell RNA sequencing (scRNA-seq) has revealed the presence of several spermatogonial clusters characterized by specific molecular signatures. However, it is unknown whether the presence of such clusters can be confirmed in terms of protein expressio...
Article
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The family of WWC proteins is known to regulate cell proliferation and organ growth control via the Hippo signaling pathway. As WWC proteins share a similar domain structure and a common set of interacting proteins, they are supposed to fulfill compensatory functions in cells and tissues. While all three WWC family members WWC1, WWC2, and WWC3 are...
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Background: A subtype of Disorders of Sex Development (DSD) in individuals with a 46,XX karyotype who are phenotypically male is classified as testicular DSD (46,XX TDSD). These individuals develop testes but are infertile due to germ cell loss. However, little is known about their testicular architecture. Methods: We analyzed biopsies of four S...
Article
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An uncontrolled reproduction of animals in human hands should be avoided. To meet this goal, animals are widely castrated, i.e., the gonads are completely removed. Since the gonads are the most important source of sex hormones, this is a serious intervention in the entire endocrine system of an organism. Sterilization is a much less invasive proced...
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Objective Germ cells of transwomen are affected by gender affirming hormone therapy (GAHT). Fertility will be lost after surgical intervention, thereby fertility preservation becomes an increasingly important topic. We investigated if the absolute number of spermatogonia in transwomen is comparable at the time of gender affirming surgery (GAS) to t...
Article
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The process of spermatogenesis—when germ cells differentiate into sperm—is tightly regulated, and misregulation in gene expression is likely to be involved in the physiopathology of male infertility. The testis is one of the most transcriptionally rich tissues; nevertheless, the specific gene expression changes occurring during spermatogenesis are...
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
Background Crypto- and azoospermia (very few/no sperm in the semen) are main contributors to male factor infertility. Genetic causes for spermatogenic failure (SPGF) include Klinefelter syndrome and Y-chromosomal azoospermia factor microdeletions, and CFTR mutations for obstructive azoospermia (OA). However, the majority of cases remain unexplained...
Preprint
Full-text available
Cell differentiation processes are highly dependent on cell stage-specific gene expression, including timely production of alternatively spliced transcripts. One of the most transcriptionally rich tissues is the testis, where the process of spermatogenesis, or generation of male gametes, takes place. To date, germ cell-specific transcriptome dynami...
Article
One of the core aims of ESHRE and other Societies, such as the International Society for Stem Cell Research (ISSCR) is the advancement of scientific understanding of treatments and cures that improve human reproductive health. In May 2021, the ISSCR released updated guidelines for Stem Cell Research and Clinical Translation (Research ISfSC, 2021)....
Article
Purpose: of the research: To achieve male fertility preservation and restoration, experimental strategies for in vitro germ cell differentiation are required. The effects of two different culture conditions on in vitro maintenance and differentiation of non-human primate germ cells was studied. Three testes from three 6-month-old marmosets were cu...
Article
Background Little information is available on steroid hormone profiles in transwomen on the day of gender affirming surgery (GAS) after gender affirming hormone therapy (GAHT). Aim We compared extended serum steroid hormone profiles of 77 transwomen with 3 different treatment regimens in order to get more insight on how GAHT changes the hormone sy...
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Despite the high incidence of male infertility, only 30% of infertile men receive a causative diagnosis. To explore the 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 in the crypto spermatogonial compartment...
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Background Anti-Müllerian hormone (AMH) and inhibin B are produced by Sertoli cells. AMH secretion indicates an immature Sertoli cell state. Inhibin B serves as a marker of male fertility. Identification of markers reflecting the presence of germ cells is of particular relevance in trans*persons undergoing gender affirming hormone therapy (GAHT), i...
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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...
Preprint
Full-text available
Despite the high incidence of male infertility, about 70% of infertile men do not receive a causative diagnosis. To gain insights into the regulatory mechanisms governing human germ cell function in normal and impaired spermatogenesis (cryptozoospermic patients, crypto), we combined single cell RNA sequencing (>30.000 cells), proteome, and histomor...
Article
Delayed family planning and increased parental age increases the risk for infertility and impaired offspring health. While the impact of ageing on oogenesis is well studied, on spermatogenesis this is less understood. Assessing ageing effects on the male germline presents the challenge of differentiating between the effects of ageing-associated mor...
Article
Specification of germ cell-like cells from induced pluripotent stem cells (iPSCs) has become a clinically relevant tool for research. Research on initial embryonic processes is often limited by the access to fetal tissue, and in humans the molecular events resulting in primordial germ cell (PGC) specification and sex determination remain to be eluc...
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Hypergonadotropic hypogonadism is a major feature of Klinefelter syndrome (KS), assumed to be caused by testicular hormone resistance. It was previously shown that intratesticular testosterone levels in vivo and Leydig cell function in vitro seem to be normal indicating other functional constraints. We hypothesized that impaired testicular vascular...
Article
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 in 58 men with unexplained meio...
Article
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Signalling pathways and cellular interactions defining initial processes of testis morphogenesis, i.e. cord formation, are poorly understood. In vitro cell-based systems modelling cord formation can be utilised as platforms to interrogate processes of tubulogenesis. We aimed at testing our established cord formation in vitro model using adult human...
Article
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Klinefelter syndrome (KS, 47,XXY) is the most frequent male chromosomal aneuploidy resulting in a highly heterogeneous clinical phenotype associated with hormonal dysbalance, increased rate of co‐morbidities, and reduced lifespan. Two hallmarks of KS‐affecting testicular functions are consistently observed: Hypergonadotropic hypogonadism and germ c...
Article
Successful in vitro spermatogenesis was reported using immature mouse testicular tissues in a fragment culture approach, raising hopes that this method could also be applied for fertility preservation in humans. Although maintaining immature human testicular tissue fragments in culture is feasible for an extended period, it remains unknown whether...
Article
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Background: A genetic variant within the FSHB gene can deviate FSH action on spermatogenesis. The c.-211G > T FSHB single nucleotide polymorphism impacts FSHB transcription and biosynthesis due to interference with the LHX3 transcription factor binding. This SNP was previously shown to be strongly associated with lowered testicular volume, reduced...
Article
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Cancer therapy and conditioning treatments of non-malignant diseases affect spermatogonial function and may lead to male infertility. Data on the molecular properties of spermatogonia and the influence of disease and/or treatment on spermatogonial subpopulations remain limited. Here, we assessed if the density and percentage of spermatogonial subpo...
Conference Paper
Full-text available
Male infertility can be caused by genetic defects or anti-cancer therapy. Due to lacking fertility preservation options, especially prepubertal boys with malignant diseases not capable to cryopreserve sperm have poor prospects to father their own children. To date, immature testicular tissues are preserved with the perspective to develop in vitro s...
Preprint
Full-text available
Male infertility affects ~7% of men in Western societies, but its causes remain poorly understood. The most clinically severe form of male infertility is non-obstructive azoospermia (NOA), which is, in part, caused by an arrest at meiosis, but so far only few genes have been reported to cause germ cell arrest in males. To address this gap, whole ex...
Article
Full-text available
Background: The most common sex chromosomal aneuploidy in males is Klinefelter syndrome, which is characterized by at least one supernumerary X chromosome. While these men have long been considered infertile, focal spermatogenesis can be observed in some patients, and sperm can be surgically retrieved and used for artificial reproductive technique...
Article
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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
Evidence of an age-related increase of β-synuclein (SNCB) in several parts of the visual system including the retina has been reported. SNCB is thought to function as an antagonist of α-synuclein in neurodegenerative diseases, but the exact role of SNCB remains unclear. The presented work studies two different aspects of the onset and role of SNCB...
Article
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Human spermatogonia are target for exploration of adult stem cell characteristics and potential source for the development of therapeutic applications. Almost 50 years ago, Yves Clermont stated with regard to the nature of the true stem cells: 'there is the possibility that other classes of spermatogonia exist beside the three classes (Adark, Apale...
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STUDY QUESTION: Can full spermatogenesis be achieved after xenotransplantation of prepubertal primate testis tissue to the mouse, in testis or subcutaneously? SUMMARY ANSWER: Intratesticular xenotransplantation supported the differentiation of immature germ cells from marmoset (Callithrix jacchus) into spermatids and spermatozoa at 4 and 9 months p...
Conference Paper
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Heutzutage wird der Kinderwunsch sozio-ökonomisch bedingt zunehmend auf spätere Lebensphasen verschoben. Neben bekannten Einflüssen mütterlichen Alters, mehren sich die Hinweise eines negativen Einflusses auf die Kindsgesundheit durch ein höheres Alter des Vaters. Eine Rolle könnten hierbei bspw. Mutationen oder epigenetische Keimbahnveränderungen,...
Article
For the reason that adult Sertoli cell specific connexin 43 knockout (SCCx43KO) mice show arrested spermatogenesis at spermatogonial level or Sertoli cell only tubules and significantly reduced germ cell (GC) numbers, the aims of the present study were (1) to characterize the remaining GC population and (2) to elucidate possible mechanisms of their...
Article
Significance: The current study characterized the different protein profiles of the retinal pigment epithelium (RPE) of the macula-bearing, non-human primate Callithrix jacchus during life-time. In addition, the subproteomes of macular and peripheral RPE were investigated. Differently expressed proteins described developmental processes in neonate...
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...
Article
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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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Purpose: Extensive follicle loss has been demonstrated in ovarian grafts post transplantation, reducing their productivity and lifespan. Several mechanisms for this loss have been proposed, and this study aims to clarify when and how the massive follicle loss associated with transplantation of ovarian tissue graft occurs. An understanding of the m...
Chapter
Klinefelter syndrome (KS) is a frequent (0.2%) sex-chromosomal disorder of males presenting with a 47,XXY karyotype. This condition is associated with infertility, hypogonadism, metabolic, and cognitive impairments. As experimental research is restrictive in patients, animal models for KS are needed to explore its molecular and genetic underpinning...
Article
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Klinefelter Syndrome (KS), the most common chromosomal disorder in men (47,XXY), is associated with numerous comorbidities. Based on a number of isolated case reports, we performed the first systematic and comprehensive evaluation of eye health in KS patients with a focus on ocular structure and vascularization. Twenty-one KS patients and 26 male a...
Article
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Over the past few decades, several studies have attempted to decipher the biology of mammalian germline stem cells (GSCs). These studies provide evidence that regulatory mechanisms for germ cell specification and migration are evolutionarily conserved across species. The characteristics and functions of primate GSCs are highly distinct from rodent...
Article
Purpose: To evaluate repeatability of the quantitative analysis of vessel density in the retinas of healthy mice using optical coherence tomography angiography (OCT-A). Methods: Seventeen eyes of seventeen healthy mice aged 10-15 weeks (young) and 75-95 weeks (old) were included in this study. OCT-A was performed using RTVue XR Avanti (Optovue I...
Article
Study question: Does irradiation evoke adverse effects in germ and somatic cells in testis xenografts from prepubertal monkeys? Summary answer: In addition to the expected depletion of germ cells, a dose-dependent effect of irradiation was observed at the mRNA and protein level in Sertoli and peritubular myoid cells. What is known already: Tes...
Article
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The timing of de novo DNA methylation in male germ cells during human testicular development is yet unsolved. Apart from that, the stability of established imprinting patterns in vitro is controversially discussed. This study aimed at determining the timing of DNA de novo methylation and at assessing the stability of the methylation status in vitro...
Conference Paper
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Table of contents O1 Regulation of genes by telomere length over long distances Jerry W. Shay O2 The microtubule destabilizer KIF2A regulates the postnatal establishment of neuronal circuits in addition to prenatal cell survival, cell migration, and axon elongation, and its loss leading to malformation of cortical development and severe epilepsy No...
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Currently, the amount of sequenced and classified MHC class I genes of the common marmoset is very limited, in spite of the wide use as animal model for biomedical research. In this study, 480 clones of MHC class I G locus (Caja-G) cDNA sequences were obtained from 21 common marmosets. Up to ten different alleles were detected in each common marmos...
Article
Background An adequate and undisturbed generation of fertile sperm is a prerequisite for fatherhood. Therefore, spermatogenesis is of central importance for male fertility. The testes, however, not only hold the germinal epithelium as the sperm-generating organ but also acts as a gland releasing androgens to control male reproductive function. This...
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Following the 1st International Workshop on the Klinefelter Syndrome in 2010 (Juul et al., 2011), the 2nd IWKS took place in Munster, Germany from March 10 to 12, 2016 and was organized by the Centre of Reproductive Medicine and Andrology of the University of Munster. During the program, talks were presented by leading researchers in the field foll...
Article
Background: Hypothalamic kisspeptin-kisspeptin receptor signalling in primates ensures the successful progression into puberty during development and maintenance of reproductive capacity during adulthood. Human testis has been shown to express high-to-moderate levels of kisspeptin and kisspeptin receptor gene expression. In this study, we aimed at...
Article
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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...
Conference Paper
Introduction: Gender Dysphoria (GD) is characterized by the urge to live as member of the desired sex, different to natal sex. The goal of medical and surgical treatment is to improve the well-being and quality of life of transpeople [Meriggiola et al. 2015]. Sex re- assignment requires a multidisciplinary treat- ment [Hembree et al. 2009] includin...
Article
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Introduction: Cross-sex hormone treatment of gender dysphoria (GD) patients changing from male to female a prerequisite for sex reassignment. For initial physical adaptation, a combined treatment of anti-androgens and estrogens is used. Provided that patients fulfill specific criteria, sex reassignment surgery (SRS) presents the final step toward p...
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
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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
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The common marmoset (Callithrix jacchus) is a New World primate that exhibits a man-like adult testicular organization. Aims: this study examines the pubertal testicular development in the common marmoset. Material and methods: immature male common marmosets (n = 48) were monitored longitudinally for a period of 13 months. Body weight and testicula...
Article
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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...
Chapter
In this chapter we review the data available on the use of marmosets as a valuable NHP model and report on histopathological specificities in a variety of organs. Based on the differences described, the marmoset model is discussed in the context of toxicological safety assessments as well as a model for general research on the pathophysiology of hu...
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
Testosterone deficiency in Klinefelter syndrome (KS) was thought to result from disturbed Leydig cell (LC) function. However, in a KS mouse model (41,XXY*), LCs were found to be hyperplastic and hyper-reactive. Furthermore, intratesticular testosterone (ITT) concentrations were comparable to controls with a normal karyotype. We confirmed this in a...
Article
The Sertoli cell (SC)-specific knockout (KO) of connexin43 (Cx43) results in spermatogenic arrest at the level of spermatogonia and/or SC-only syndrome. Histology of the interstitial compartment suggests Leydig cell (LC) hyperplasia. Our aim has been to investigate possible effects of the SC-specific KO of Cx43 (SCCx43KO) on interstitial LC. We the...