Nina Neuhaus

Nina Neuhaus
Universitätsklinikum Münster | UKM · Centrum für Reproduktionsmedizin und Andrologie

Dr. rer. nat.

About

70
Publications
7,129
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1,178
Citations
Citations since 2016
37 Research Items
888 Citations
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2016201720182019202020212022050100150200

Publications

Publications (70)
Article
Full-text available
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
The amount of single-cell RNA-sequencing (scRNA-seq) data produced in the field of human male reproduction has steadily increased. Transcriptional profiles of thousands of testicular cells have been generated covering the human neonatal, prepubertal, pubertal and adult period as well as different types of male infertility; the latter include non-ob...
Article
Full-text available
Background Several studies have reported an association between male infertility and aberrant sperm DNA methylation patterns, in particular in imprinted genes. In a recent investigation based on whole methylome and deep bisulfite sequencing, we have not found any evidence for such an association, but have demonstrated that somatic DNA contamination...
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...
Article
Full-text available
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...
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...
Article
Full-text available
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...
Article
Full-text available
Objective To normalize age-dependent effects on standardized measures of spermatogonial quantity such as the number of spermatogonia per tubular cross-section (S/T) or fertility index. Design Published quantitative histologic data on human spermatogonial numbers were used to create Z-scores for reference means and tested on archived testicular tis...
Article
Full-text available
Mutations affecting the germline can result in infertility or the generation of germ cell tumors (GCT), highlighting the need to identify and characterize the genes controlling germ cell development. The RNA-binding protein and E3 ubiquitin ligase TRIM71 is essential for embryogenesis, and its expression has been reported in GCT and adult mouse tes...
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...
Preprint
Full-text available
Mutations affecting the germline can result in infertility or the generation of germ cell tumors (GCT), highlighting the need to identify and characterize the genes controlling the complex molecular network orchestrating germ cell development. TRIM71 is a stem cell-specific factor essential for embryogenesis, and its expression has been reported in...
Article
Full-text available
Background: In the past 15 years, numerous studies have described aberrant DNA methylation of imprinted genes (e.g. MEST and H19) in sperm of oligozoospermic men, but the prevalence and genomic extent of abnormal methylation patterns have remained unknown. Results: Using deep bisulfite sequencing (DBS), we screened swim-up sperm samples from 40...
Article
Zusammenfassung Wir stimmen dem in der Leitlinie genannten starken Konsens für Maßnahmen der Reproduktionsmedizin als wichtige Option zur Erfüllung des Kinderwunsches bei trans Personen uneingeschränkt zu. Informationen über diese Maßnahmen müssen Bestandteil von Behandlungen von trans Personen sein. Die geschlechtsangleichende Hormontherapie bei M...
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
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
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...
Preprint
Full-text available
Background In the past 15 years, numerous studies have described aberrant DNA methylation of imprinted genes (e.g. MEST and H19 ) in sperm of infertile patients, but the prevalence and genomic extent of abnormal methylation patterns have remained unknown. Results Using deep bisulfite sequencing (DBS), we screened swim-up sperm samples from 40 norm...
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
Full-text available
Background From a biological and clinical perspective, it is imperative to establish primate spermatogonial cultures. Due to limited availability of human testicular tissues, the macaque (Macaca fascicularis) was employed as non-human primate model. The aim of this study was to characterize the expression of somatic as well as germ cell markers in...
Article
Full-text available
Fertility preservation in trans women is a crucial but thus far neglected component in the gender confirming treatment in Germany. It is difficult for trans women to access reproductive health care because centers offering treatment, psychological guidance, gender confirming surgery, as well as reproductive health services are scarce in Germany. Le...
Article
Grafting of immature monkey testis tissue enables generation of sperm and offspring
Article
Full-text available
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...
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
In zebrafish, action of the chemokine Cxcl12 is mediated through its G-protein coupled seven-transmembrane domain receptor Cxcr4 and the atypical receptor Cxcr7. Employing this animal model it was revealed that this Cxcl12 signalling system plays a crucial role for directed migration of primordial germ cells (PGC) during early testicular developmen...
Chapter
The de novo creation of spermatozoa is an important task in reproductive research. Patients with spermatogenic defects, especially those impacted by gonadotoxic oncological treatments, would benefit from this approach. Several in vitro methods for differentiation of spermatogonia into sperm are under development. These approaches include organ cult...
Article
Full-text available
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
Full-text available
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
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
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...
Article
Full-text available
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...
Article
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The study by Nettersheim et al (2016a) is a highly interesting work, revealing the potential of PRAME (preferentially expressed antigen of melanoma) for diagnostic discrimination of human type II germ cell cancers. Moreover, the presented data is incorporated into a model placing PRAME into a decisive position for the cell fate choice with regard t...
Article
Editorial written by Dr. Nina Neuhaus to our publication 'The cancer/testis-antigen PRAME supports the pluripotency network and represses somatic and germ cell differentiation programs in seminomas'. The study by Nettersheim et al (2016a) is a highly interesting work, revealing the potential of PRAME (preferentially expressed antigen of melanoma)...
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
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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 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...
Article
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In mice the chemokine Cxcl12 and its receptor Cxcr4 participate in maintenance of the spermatogonial population during postnatal development. More complexity arises since Cxcl12 also binds to the non-classical/atypical chemokine receptor Cxcr7. We explored the expression pattern of Cxcl12, Cxcr4 and Cxcr7 during postnatal development in mouse teste...
Article
Study question: Can primate spermatogonial cultures be optimized by application of separation steps and well defined culture conditions? Summary answer: We identified the cell fraction which provides the best source for primate spermatogonia when prolonged culture is desired. What is known already: Man and marmoset show similar characteristics...
Patent
Full-text available
A method of in vitro maturation of adult human germ line cells in an artificial biological environment, which entails: a) isolating human spermatogonial stem cells (SSCs), and optionally purifying the same; and b) co-culturing the isolated and optionally purified SSCs with a suitably adjusted Sertoli cell environment to obtain haploid germ cells.
Conference Paper
Background The possibility to propagate human spermatogonia in vitro provides the basis for autologous spermatogonial trans- plantations and the in vitro derivation of sperm. One prerequisite for successful cul- tures of human spermatogonia is the ability to extract the highest possible numbers of these germ cells from testicular tissues. In the pa...
Conference Paper
Background The prevalence of male-to-fe- male (MtF) transsexuals in Europe is be- tween 1:11,900 and 1:45,000. According to standardized guidelines patients with gender dysphoria (GD) receive cross-sex hormone therapy for up to 2 years, which includes the inhibition of androgen secretion and supple- mentation of estrogens, to feminize their bodies...
Article
Full-text available
Does a combined approach allow for the unequivocal detection of human germ cells and particularly of spermatogonia in vitro? Based on our findings, we conclude that an approach comprising: (i) the detailed characterization of patients and tissue samples prior to the selection of biopsies, (ii) the use of unambiguous markers for the characterization...
Article
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TCam-2 cells are the main in vitro model for investigations into seminomatous tumors. However, despite their widespread use, questions remain regarding the cells' homogeneity and consequently how representative they are of seminomas. We assess the TCam-2 cell line using routine and novel authentication methods to determine its homogeneity, identify...
Article
The luteinizing hormone/chorionic gonadotropin receptor (LHCGR) is essential for normal male sex differentiation. Recently, the additional primate-specific exon 6A of the LHCGR was discovered and it was shown to act as regulatory element at the transcriptional level. Compound heterozygous mutations in exon 6A (c.580A>G) and exon 11 (c.1244T>C) were...
Article
Im Rahmen einer Krebstherapie kommt es häufig zu einer vorübergehenden oder dauerhaften Beeinträchtigung der Spermatogenese. Da der Fertilitätsverlust für Patienten mit Kinderwunsch eine Einschränkung der Lebensqualität bedeutet, wird erwachsenen Patienten vor Beginn der Krebstherapie die Kryokonservierung von Spermien empfohlen. Dieser Ansatz ermö...
Article
Full-text available
The marmoset monkey is a valuable model in reproductive medicine. While previous studies have evaluated germ cell dynamics in the postnatal marmoset, the features of testicular somatic cells remain largely unknown. Therefore, the aim of this study was to establish marmoset-specific markers for Sertoli and peritubular cells (PTCs) and to compare pro...
Article
Several reports have documented the derivation of pluripo-tent cells (multipotent germline stem cells) from spermato-gonial stem cells obtained from the adult mouse testis. These spermatogonia-derived stem cells express embryonic stem cell markers and differentiate to the three primary germ layers, as well as the germline. Data indicate that deriva...
Chapter
Embryonic stem cells (ESCs) are derived from the inner cell mass (ICM) of blastocysts and are characterized by the ability to differentiate into the three primary germ layers. Evidence shows, however, that the cells of the ICM and derived ESCs are not identical. Expression of early germ cell–specific markers in undifferentiated ESCs and the ability...
Article
Full-text available
Several reports have documented the derivation of pluripotent cells (multipotent germline stem cells) from spermatogonial stem cells obtained from the adult mouse testis. These spermatogonia-derived stem cells express embryonic stem cell markers and differentiate to the three primary germ layers, as well as the germline. Data indicate that derivati...
Article
Full-text available
Male pseudohermaphroditism, or Leydig cell hypoplasia (LCH), is an autosomal recessive disorder in individuals with a 46,XY karyotype, characterized by a predominantly female phenotype, a blind-ending vagina, absence of breast development, primary amenorrhea, and the presence of testicular structures. It is caused by mutations in the luteinizing ho...
Data
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Functional Characterization of the T461I and the G558C Mutations (A) Signal transduction hCG-dependent cAMP-responsive luciferase activity measured in wild-type LHR (filled circle), LHR-T461I mutant receptor (square), and empty expression plasmid pSG5 (triangles) expressing HEK293 cells. The hCG response of the mutant LH receptor is almost complete...
Data
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Exon 6A: Sequence Comparison, Phylogeny, and Genomic Organization (A) Upper part: Genomic and cDNA nucleotide sequence comparison of exon 6A from human (Homo sapiens), chimpanzee (Pan troglodytes), cynomolgus monkey (Macaca fascicularis), marmoset (Callithrix jacchus), and lemur (Eulemur coronatus). Identical nucleotides are indicated by an asteris...
Data
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Immunofluorescence Localization of HA-Tagged LHCGR Proteins in Transiently Transfected COS7 Cells (A) HA-tagged, wild-type terminal exon 6A LHCGR. (B) HA-tagged, A557C terminal exon 6A LHCGR. (C) Full-length HA-tagged LHCGR protein. Both truncated LHCGR variants, wild-type and mutated, show a predominantly intracellular localization (A and B), whil...
Data
Distribution of Exon 6A SNPs in Patients and Controls (42 KB DOC)
Data
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Revised Complete Genomic Organization of the Human LHCGR Gene Now Consisting of 12 Exons Exon sizes are given above the boxes, intron sizes below. (9 KB PDF)
Data
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