Sexual Development : Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation

BACKGROUND: Persistent müllerian duct syndrome (PMDS) is characterized by the persistence of müllerian duct derivatives in otherwise normally virilized 46,XY males. Biallelic mutations of the anti-müllerian hormone (AMH) and AMH receptor type 2 (AMHR2) genes lead to PMDS type 1 and 2, respectively. AIM: The aims of the study were to report the clinical, hormonal, and genetic findings in a patient with PMDS and discuss surgical strategies to achieve successful orchidopexy...

Abstracts of the 11th I-DSD Symposium.

No abstract text is available yet for this article.

BACKGROUND: Encompassing about half of the 60,000 species of vertebrates, fish display the greatest diversity of sex determination mechanisms among metazoans. As such that phylum offers a unique playground to study the impressive variety of gonadal morphogenetic strategies, ranging from gonochorism, with either genetic or environmental sex determination, to unisexuality, with either simultaneous or consecutive hermaphroditism. SUMMARY: From the two main types of gonads, the ovaries embrace the important role to produce the larger and non-motile gametes, which is the basis for the development of a future organism...

INTRODUCTION: Hermaphroditism is a mode of reproduction involving an individual animal that possesses both a testis and an ovary either sequentially or simultaneously. The mechanism creating hermaphrodites remains unknown. Previously, we identified foxl3 as the germline sex determination gene in a gonochoristic fish, medaka (Oryzias latipes). foxl3 loss-of-function (foxl3-/-) females produce functional sperm as well as eggs in the ovary. However, these two gametes are not self-fertilizing because of the histological separation of each gamete production...

BACKGROUND: Reptiles and amphibians provide untapped potential for discovering how a diversity of genetic pathways and environmental conditions are incorporated into developmental processes that can lead to similar functional outcomes. These groups display a multitude of reproductive strategies, and whereas many attributes are conserved within groups and even across vertebrates, several aspects of sexual development show considerable variation. SUMMARY: In this review, we focus our attention on the development of the reptilian and amphibian ovary...

BACKGROUND: Oocytes are a finite and non-renewable resource that are maintained in primordial follicle structures. The ovarian reserve is the totality of primordial follicles, present from birth, within the ovary and its establishment, size, and maintenance dictates the duration of the female reproductive lifespan. Understanding the cellular and molecular dynamics relevant to the establishment and maintenance of the reserve provides the first steps necessary for modulating both individual human and animal reproductive health as well as population dynamics...

No abstract text is available yet for this article.

Recently, a series of recurrent missense variants in the RNA-helicase DHX37 have been reported associated with either 46,XY gonadal dysgenesis, 46,XY testicular regression syndrome (TRS), or anorchia. All affected children have non-syndromic forms of disorders/differences of sex development (DSD). These variants, which involve highly conserved amino acids within known functional domains of the protein, are predicted by in silico tools to have a deleterious effect on helicase function. DHX37 is required for ribosome biogenesis in eukaryotes, and how these variants cause DSD is unclear...

The 5α-reductase type 2 enzyme catalyzes the conversion of testosterone into dihydrotestosterone, playing a crucial role in male development. This enzyme is encoded by the SRD5A2 gene, which maps to chromosome 2 (2p23), consists of 5 exons and 4 introns, and encodes a 254 amino acid protein. Disruptions in this gene are the molecular etiology of a subgroup of differences of sex development (DSD) in 46,XY patients. Affected individuals present a large range of external genitalia undervirilization, ranging from almost typically female external genitalia to predominantly typically male external genitalia with minimal undervirilization, including isolated micropenis...

INTRODUCTION: NR5A1 is an essential transcription factor that regulates several target genes involved in reproduction and endocrine function. Pathogenic variants in this gene are responsible for a wide spectrum of disorders/differences of sex development (DSD). METHODS: The molecular study involved Sanger sequencing, in vitro assays, and whole exome sequencing (WES). RESULTS: Four variants were identified within the NR5A1 non-coding region in 3 patients with 46,XY DSD...

SOX genesare master regulatory genes controlling development and are fundamental to the establishment of sex determination in a multitude of organisms. The discovery of the master sex-determining gene SRY in 1990 was pivotal for the understanding of how testis development is initiated in mammals. With this discovery, an entire family of SOX factors were uncovered that play crucial roles in cell fate decisions during development. The importance of SOX genes in human reproductive development is evident from the various disorders of sex development (DSD) upon loss or overexpression of SOX gene function...

INTRODUCTION: People with differences of sex development (DSD) and their families need education about these conditions while receiving emotional and peer support to participate in shared decision-making, reduce social isolation, and optimize physical and psychosocial outcomes. Barriers to education and support include limited knowledge and awareness by healthcare providers, tension among patient and medical communities, varied quality of educational resources, and the sensitive nature of DSD...

Reaching a firm diagnosis is vital for the long-term management of a patient with a difference or disorder of sex development (DSD). This is especially the case in XY DSD where the diagnostic yield is particularly low. Molecular genetic technology is playing an increasingly important role in the diagnostic process, and it is highly likely that it will be used more often at an earlier stage in the diagnostic process. In many cases of DSD, the clinical utility of molecular genetics is unequivocally clear, but in many other cases there is a need for careful exploration of the benefit of genetic diagnosis through long-term monitoring of these cases...

BACKGROUND: Germ cells are critical for the survival of our species. They are the only cells that undergo meiosis - the reductive form of cell division that is necessary for genetic reassortment of chromosomes and production of the haploid gametes, the sperm and eggs. Remarkably, the initial female/male fate decision in fetal germ cells does not depend on whether they are chromosomally XX or XY; rather, initial sexual fate is imposed by influences from the surrounding tissue. In mammals, the female germline is particularly precious: despite recent suggestions that germline stem cells exist in the ovary, it is still generally accepted that the ovarian reserve is finite, and its size is dependant on germ cells of the fetal ovary initiating meiosis in a timely manner...

INTRODUCTION: Sex determination in eutherian mammals is controlled by the Y-linked gene Sry, which drives the formation of testes in male embryos. Despite extensive study, the genetic steps linking Sry action and male sex determination remain largely unknown. Here, we focused on Mmd2, a gene that encodes a member of the progestin and adipoQ receptor (PAQR) family. Mmd2 is expressed during the sex-determining period in XY but not XX gonads, suggesting a specific role in testis development...

BACKGROUND: The anti-müllerian hormone (Amh) pathway is crucial for sexual development in teleosts. A male-specific duplicate of anti-müllerian hormone (amhby) was previously identified as the northern pike (Esox lucius) master sex determination gene. However, the role of its putative cognate receptor, i.e., the anti-müllerian hormone receptor type 2 (amhrII) was unclear in this species. OBJECTIVE: Here, we investigated the role of amhrII during sexual development of northern pike...

Pathogenic variants in the MAP3K1 gene are an important cause of 46,XY non-syndromic partial and complete gonadal dysgenesis, accounting for at least 4% of cases. Inheritance occurs in a sex-limited, autosomal dominant fashion with virtually complete penetrance in 46,XY individuals. 46,XX carriers appear to have normal fertility and no developmental abnormalities. Pathogenic variants occur almost exclusively within known domains of the MAP3K1 protein, facilitating annotation when identified. Where studied, these variants have been modeled to alter the local MAP3K1 folding and surface domains and have been shown to alter interactions with known binding partners...

Sex development is an intricate and crucial process in all vertebrates that ensures the continued propagation of genetic diversity within a species, and ultimately their survival. Perturbations in this process can manifest as disorders/differences of sex development (DSD). Various transcriptional networks have been linked to development of the gonad into either male or female, which is actively driven by a set of genes that function in a juxtaposed manner and is maintained through the developmental stages to preserve the final sexual identity...

BACKGROUND: Whether to produce sperm or eggs is the most basic and important choice from the perspective of germ cell development and differentiation. However, the induction mechanism has not received much attention until relatively recently. This is because the issue of sexual differentiation has generally been considered a theme of somatic cells to make a testis or ovary. Basically, the sex of individual somatic cells and germ cells matches. Therefore, the sex of germ cells is thought to follow the sex of somatic cells once determined...