Hyperthyroidism induced by paraneoplastic human chorionic gonadotropin (hCG) production from testicular tumours: a retrospective clinical and histopathological study.

Human chorionic gonadotropin (hCG) has structural similarities with thyroid-stimulating hormone (TSH) and may stimulate TSH receptors at higher concentrations. During pregnancy, placental hCG causes TSH suppression, contributing to hyperemesis. However, in males, clinical manifestations caused by excess hCG are rare.

Identification of two hidden clinical subgroups among men with idiopathic cryptozoospermia.

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 below 0.1 million/ml.

Male minipuberty in human and non-human primates: planting the seeds of future fertility.

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: Minipuberty is a transient activity period of the hypothalamic-pituitary-gonadal (HPG) axis in the postnatal and infant period in humans and non-human primates.

Interplay of spermatogonial subpopulations during initial stages of spermatogenesis in adult primates.

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 expression and whether protein expression in the subsets overlaps.

WWC2 expression in the testis: Implications for spermatogenesis and male fertility.

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 found co-expressed in most human organs including lung, brain, kidney, and liver, in the testis only WWC2 displays a relatively high expression.

Testicular Architecture of Men with 46,XX Testicular Disorders of Sex Development.

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.

Effects of castration and sterilization on baseline and response levels of cortisol-A case study in male guinea pigs.

An uncontrolled reproduction of animals in human hands should be avoided. To meet this goal, animals are widely castrated, i.e.

New perspectives on fertility in transwomen with regard to spermatogonial stem cells.

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 imortant topic. This study investigated if the absolute number of spermatogonia in transwomen is comparable at the time of gender-affirming surgery (GAS) to that in pre-pubertal boys.

Transcriptome analyses in infertile men reveal germ cell-specific expression and splicing patterns.

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 not fully understood. To better understand gene expression during spermatogenesis, we generated germ cell-specific whole transcriptome profiles by systematically comparing testicular transcriptomes from tissues in which spermatogenesis is arrested at successive steps of germ cell differentiation.

Analysis of copy number variation in men with non-obstructive azoospermia.

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.

Genetic Architecture of Azoospermia-Time to Advance the Standard of Care.

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 because monogenic causes are not analysed.

Limited spermatogenic differentiation of testicular tissue from prepubertal marmosets (Callithrix jacchus) in an in vitro organ culture system.

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 cultured using a gas-liquid interphase system for 12 days.

New Insights Into Extended Steroid Hormone Profiles in Transwomen in a Multi-Center Setting in Germany.

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 system.

Methods: Samples were obtained from 3 independent clinics.

Serum and intratesticular inhibin B, AMH, and spermatogonial numbers in trans women at gender-confirming surgery: An observational study.

Background: Anti-Müllerian hormone and inhibin B are produced by Sertoli cells. Anti-Müllerian hormone secretion indicates an immature Sertoli cell state. Inhibin B serves as a marker of male fertility.

Testicular function in males with infantile nephropathic cystinosis.

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 fatherhood.

What Is Known Already: Biallelic mutations in the cystinosin (CTNS) gene in INC cause dysfunction in cystine transport across lysosomal membranes and cystine accumulation throughout the body. Spontaneous paternity in cystinosis has not been described, despite the availability of cysteamine treatment.

Healthy ageing and spermatogenesis.

Delayed family planning and increased parental age increase the risk for infertility and impaired offspring health. While the impact of ageing on oogenesis is well studied, this is less understood on spermatogenesis. Assessing ageing effects on the male germline presents a challenge in differentiating between the effects of ageing-associated morbidities, infertility and 'pure' ageing.

A novel xeno-organoid approach: exploring the crosstalk between human iPSC-derived PGC-like and rat testicular cells.

Specification of germ cell-like cells from induced pluripotent stem cells has become a clinically relevant tool for research. Research on initial embryonic processes is often limited by the access to foetal tissue, and in humans, the molecular events resulting in primordial germ cell (PGC) specification and sex determination remain to be elucidated. A deeper understanding of the underlying processes is crucial to describe pathomechanisms leading to impaired reproductive function.

Testicular blood supply is altered in the 41,XX* Klinefelter syndrome mouse model.

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 vascularization/blood flow could be a co-factor to the observed hypergonadotropic hypogonadism.

Bi-allelic Mutations in M1AP Are a Frequent Cause of Meiotic Arrest and Severely Impaired Spermatogenesis Leading to Male Infertility.

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.

Adapting the 3D-printed Openflexure microscope enables computational super-resolution imaging.

We report on a 3D printed microscope, based on a design by the Openflexure project, that uses low cost components to perform fluorescence imaging. The system is sufficiently sensitive and mechanically stable to allow the use of the Super Resolution Radial Fluctuations algorithm to obtain images with resolution better than the diffraction limit. Due to the low-cost components, the entire system can be built for approximately $1200.

Challenging human somatic testicular cell reassembly by protein kinase inhibition -setting up a functional in vitro test system.

Signalling pathways and cellular interactions defining initial processes of testis morphogenesis, i.e. cord formation, are poorly understood.

41,XX * male mice: An animal model for Klinefelter syndrome.

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 cell (GC) loss resulting in infertility. Although KS is being studied for decades, the underlying mechanisms for the observed pathophysiology are still unclear.

The initial maturation status of marmoset testicular tissues has an impact on germ cell maintenance and somatic cell response in tissue fragment culture.

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 germ cell survival and the somatic cell response depend on the differentiation status of tissue. Employing the marmoset monkey (Callithrix jacchus), we aimed to assess whether the maturation status of prepubertal and peri-/pubertal testicular tissues influence the outcome of testis fragment culture.

Does the FSHB c.-211G>T polymorphism impact Sertoli cell number and the spermatogenic potential in infertile patients?

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.