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Journal of Assisted Reproduction and... Apr 2016The study aims to discuss the effects of aging on the male reproductive system. A systematic review was performed using PubMed from 1980 to 2014. Aging is a natural... (Review)
Review
The study aims to discuss the effects of aging on the male reproductive system. A systematic review was performed using PubMed from 1980 to 2014. Aging is a natural process comprising of irreversible changes due to a myriad of endogenous and environmental factors at the level of all organs and systems. In modern life, as more couples choose to postpone having a child due to various socioeconomic reasons, research for understanding the effects of aging on the reproductive system has gained an increased importance. Paternal aging also causes genetic and epigenetic changes in spermatozoa, which impair male reproductive functions through their adverse effects on sperm quality and count as, well as, on sexual organs and the hypothalamic-pituitary-gonadal axis. Hormone production, spermatogenesis, and testes undergo changes as a man ages. These small changes lead to decrease in both the quality and quantity of spermatozoa. The offspring of older fathers show high prevalence of genetic abnormalities, childhood cancers, and several neuropsychiatric disorders. In addition, the latest advances in assisted reproductive techniques give older men a chance to have a child even with poor semen parameters. Further studies should investigate the onset of gonadal senesce and its effects on aging men.
Topics: Aging; Cellular Senescence; Epigenesis, Genetic; Gonads; Humans; Male; Reproduction; Reproductive Techniques, Assisted; Spermatogenesis; Spermatozoa; Testis
PubMed: 26867640
DOI: 10.1007/s10815-016-0663-y -
Cell Stem Cell Jun 2017Human fetal germ cells (FGCs) are precursors to sperm and eggs and are crucial for maintenance of the species. However, the developmental trajectories and heterogeneity...
Human fetal germ cells (FGCs) are precursors to sperm and eggs and are crucial for maintenance of the species. However, the developmental trajectories and heterogeneity of human FGCs remain largely unknown. Here we performed single-cell RNA-seq analysis of over 2,000 FGCs and their gonadal niche cells in female and male human embryos spanning several developmental stages. We found that female FGCs undergo four distinct sequential phases characterized by mitosis, retinoic acid signaling, meiotic prophase, and oogenesis. Male FGCs develop through stages of migration, mitosis, and cell-cycle arrest. Individual embryos of both sexes simultaneously contain several subpopulations, highlighting the asynchronous and heterogeneous nature of FGC development. Moreover, we observed reciprocal signaling interactions between FGCs and their gonadal niche cells, including activation of the bone morphogenic protein (BMP) and Notch signaling pathways. Our work provides key insights into the crucial features of human FGCs during their highly ordered mitotic, meiotic, and gametogenetic processes in vivo.
Topics: Bone Morphogenetic Proteins; Cell Division; Embryonic Germ Cells; Female; Fetus; Gonads; High-Throughput Nucleotide Sequencing; Humans; Male; Receptors, Notch; Signal Transduction; Stem Cell Niche
PubMed: 28457750
DOI: 10.1016/j.stem.2017.03.007 -
General and Comparative Endocrinology Dec 2021Changes in expression or activation of various metalloproteases including matrix metalloproteases (Mmp), a disintegrin and metalloprotease (Adam) and a disintegrin and... (Review)
Review
Changes in expression or activation of various metalloproteases including matrix metalloproteases (Mmp), a disintegrin and metalloprotease (Adam) and a disintegrin and metalloprotease with thrombospondin motif (Adamts), and their endogenous inhibitors (tissue inhibitors of metalloproteases, Timp), have been shown to be critical for ovulation in various species from studies in past decades. Some of these metalloproteases such as Adamts1, Adamts9, Mmp2, and Mmp9 have also been shown to be regulated by luteinizing hormone (LH) and/or progestin, which are essential triggers for ovulation in all vertebrate species. Most of these metalloproteases also express broadly in various tissues and cells including germ cells and somatic gonad cells. Thus, metalloproteases likely play roles in gonad formation processes comprising primordial germ cell (PGC) migration, development of germ and somatic cells, and sex determination. However, our knowledge on the functions and mechanisms of metalloproteases in these processes in vertebrates is still lacking. This review will summarize our current knowledge on the metalloproteases in ovulation and gonad formation with emphasis on PGC migration and germ cell development.
Topics: Animals; Female; Germ Cells; Gonads; Luteinizing Hormone; Matrix Metalloproteinases; Ovulation
PubMed: 34606745
DOI: 10.1016/j.ygcen.2021.113924 -
Genome Biology Nov 2016Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult...
BACKGROUND
Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously.
RESULTS
We analyzed DNA from the largest reported international cohort of patients with DSD (278 patients with 46,XY DSD and 48 with 46,XX DSD). Our targeted gene panel compares favorably with other sequencing platforms. We found a total of 28 diagnostic genes that are implicated in DSD, highlighting the genetic spectrum of this disorder. Sequencing revealed 93 previously unreported DSD gene variants. Overall, we identified a likely genetic diagnosis in 43% of patients with 46,XY DSD. In patients with 46,XY disorders of androgen synthesis and action the genetic diagnosis rate reached 60%. Surprisingly, little difference in diagnostic rate was observed between singletons and trios. In many cases our findings are informative as to the likely cause of the DSD, which will facilitate clinical management.
CONCLUSIONS
Our massively parallel sequencing targeted DSD gene panel represents an economical means of improving the genetic diagnostic capability for patients affected by DSD. Implementation of this panel in a large cohort of patients has expanded our understanding of the underlying genetic etiology of DSD. The inclusion of research candidate genes also provides an invaluable resource for future identification of novel genes.
Topics: Chromosome Aberrations; Cohort Studies; Disorders of Sex Development; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Gonads; High-Throughput Nucleotide Sequencing; Humans; Male; Mutation; Ovary; Pedigree; Phenotype; Testis
PubMed: 27899157
DOI: 10.1186/s13059-016-1105-y -
The International Journal of... 2021Fish present remarkable malleability regarding gonadal sex fate. This phenotypic plasticity enables an organism to adapt to changes in the environment by responding with... (Review)
Review
Fish present remarkable malleability regarding gonadal sex fate. This phenotypic plasticity enables an organism to adapt to changes in the environment by responding with different phenotypes. The gonad and the brain present this extraordinary plasticity. These organs are involved in the response to environmental stressors to direct gonadal fate, inducing sex change or sex reversal in hermaphroditic and gonochoristic fish, respectively. The presence of such molecular and endocrine plasticity gives this group a large repertoire of possibilities against a continuously changing environment, resulting in the highest radiation of reproduction strategies described in vertebrates. In this review, we provide a broad and comparative view of tremendous radiation of sex determination mechanisms to direct gonadal fate. New results have established that the driving mechanism involves early response to environmental stressors by the brain plus high plasticity of gonadal differentiation and androgens as by-products of stress inactivation. In addition to the stress axis, two other major axes - the hypothalamic-pituitary-gonadal axis and the hypothalamic-pituitary-thyroid axis, which are well known for their participation in the regulation of reproduction - have been proposed to reinforce brain-gonadal interrelationships in the fate of the gonad.
Topics: Animals; Brain; Fishes; Gonads; Hypothalamo-Hypophyseal System; Reproduction; Sex Differentiation
PubMed: 32930379
DOI: 10.1387/ijdb.200072jf -
GeroScience Jun 2019Women live longer than men in virtually all circumstances. However, a more common pattern among animals is that one sex lives longer under some conditions, the other... (Review)
Review
Women live longer than men in virtually all circumstances. However, a more common pattern among animals is that one sex lives longer under some conditions, the other lives longer under other conditions. In laboratory mice, interventions that extend longevity are surprisingly often sex-specific in their effects. Understanding these conditional sex differences could provide mechanistic insight into how longevity could be modulated in humans. One way that longevity can be consistently enhanced is by inhibiting reproduction or eliminating the capacity to reproduce. Thus, there appears to be a mechanistic link between gonadal activity and longevity. There also appears to be a mechanistic link between some types of neuroendocrine signaling and longevity. Combining these two observations suggest that communication between the brain and gonad is a ripe avenue for further exploring longevity-assurance mechanisms. Also, because the timing and activity of specific brain-gonad endocrine differs between the sexes, neuroendocrine linkages between the brain and gonad, particularly among the less obvious hormones such as activin and inhibin, could provide additional insight into mechanisms of sex differences in aging.
Topics: Activins; Aging; Animals; Brain; Female; Gonads; Humans; Hypothalamo-Hypophyseal System; Inhibins; Longevity; Male; Neurosecretory Systems; Reproduction; Sex Characteristics
PubMed: 31243699
DOI: 10.1007/s11357-019-00081-3 -
Sexual Development : Genetics,... 2014Vertebrate reproduction depends on the function of 2 distinct gametes, sperm and eggs, which develop in 2 different organs, the testis and the ovary. Testes and ovaries... (Review)
Review
Vertebrate reproduction depends on the function of 2 distinct gametes, sperm and eggs, which develop in 2 different organs, the testis and the ovary. Testes and ovaries are composed of germ cells, supporting cells and interstitial cells. In this review, we describe the origin and the fate of these cell lineages and how they interact with each other to form sexually dimorphic reproductive organs in medaka. We delineate how the temporally different association and establishment of these lineages contribute to a variety of seemingly different sex differentiation processes among teleost fish. Thus, teleosts represent an intriguing group in which to study the fundamental processes of gonadal development through comparing conserved and unique mechanisms.
Topics: Animals; Female; Fishes; Gene Expression Regulation, Developmental; Gonads; Male; Ovary; Reproduction; Sex Differentiation; Testis
PubMed: 25034975
DOI: 10.1159/000364924 -
Sexual Development : Genetics,... 2022Sex development is an intricate and crucial process in all vertebrates that ensures the continued propagation of genetic diversity within a species, and ultimately their... (Review)
Review
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. One such identified gene is Chromobox homolog 2 (CBX2), an important ortholog of the Polycomb group (PcG) proteins, that functions as both chromatin modifier and highly dynamic transactivator. CBX2 was shown to be an essential factor for gonadal development in mammals, as genetic variants or loss-of-function of CBX2 can cause sex reversal in mice and humans. Here we will provide an overview of CBX2, its biological functions at molecular level, and the CBX2-dependent transcriptional landscape in gonadal development and DSD.
Topics: Animals; Female; Humans; Male; Mice; Gonads; Polycomb Repressive Complex 1; Sexual Development
PubMed: 35263754
DOI: 10.1159/000522164 -
The FEBS Journal May 2022Gonad development is a highly regulated process that coordinates cell specification and morphogenesis to produce sex-specific organ structures that are required for... (Review)
Review
Gonad development is a highly regulated process that coordinates cell specification and morphogenesis to produce sex-specific organ structures that are required for fertility, such as testicular seminiferous tubules and ovarian follicles. While sex determination occurs within specialized gonadal supporting cells, sexual differentiation is evident throughout the entire organ, including within the interstitial compartment, which contains immune cells and vasculature. While immune and vascular cells have been traditionally appreciated for their supporting roles during tissue growth and homeostasis, an increasing body of evidence supports the idea that these cell types are critical drivers of sexually dimorphic morphogenesis of the gonad. Myeloid immune cells, such as macrophages, are essential for multiple aspects of gonadogenesis and fertility, including for forming and maintaining gonadal vasculature in both sexes at varying stages of life. While vasculature is long known for supporting organ growth and serving as an export mechanism for gonadal sex steroids in utero, it is also an important component of fetal testicular morphogenesis and differentiation; additionally, it is vital for ovarian corpus luteal function and maintenance of pregnancy. These findings point toward a new paradigm in which immune cells and blood vessels are integral components of sexual differentiation and organogenesis. In this review, we discuss the state of the field regarding the diverse roles of immune and vascular cells during organogenesis of the testis and ovary and highlight outstanding questions in the field that could stimulate new research into these previously underappreciated constituents of the gonad.
Topics: Female; Gonads; Humans; Male; Organogenesis; Ovary; Pregnancy; Sex Differentiation; Testis
PubMed: 33774913
DOI: 10.1111/febs.15848 -
International Journal of Molecular... Nov 2020Cadherins are a group of membrane proteins responsible for cell adhesion. They are crucial for cell sorting and recognition during the morphogenesis, but they also play... (Review)
Review
Cadherins are a group of membrane proteins responsible for cell adhesion. They are crucial for cell sorting and recognition during the morphogenesis, but they also play many other roles such as assuring tissue integrity and resistance to stretching, mechanotransduction, cell signaling, regulation of cell proliferation, apoptosis, survival, carcinogenesis, etc. Within the cadherin superfamily, E- and N-cadherin have been especially well studied. They are involved in many aspects of sexual development and reproduction, such as germline development and gametogenesis, gonad development and functioning, and fertilization. E-cadherin is expressed in the primordial germ cells (PGCs) and also participates in PGC migration to the developing gonads where they become enclosed by the N-cadherin-expressing somatic cells. The differential expression of cadherins is also responsible for the establishment of the testis or ovary structure. In the adult testes, N-cadherin is responsible for the integrity of the seminiferous epithelium, regulation of sperm production, and the establishment of the blood-testis barrier. Sex hormones regulate the expression and turnover of N-cadherin influencing the course of spermatogenesis. In the adult ovaries, E- and N-cadherin assure the integrity of ovarian follicles and the formation of corpora lutea. Cadherins are expressed in the mature gametes and facilitate the capacitation of sperm in the female reproductive tract and gamete contact during fertilization. The germ cells and accompanying somatic cells express a series of different cadherins; however, their role in gonads and reproduction is still unknown. In this review, we show what is known and unknown about the role of cadherins in the germline and gonad development, and we suggest topics for future research.
Topics: Animals; Cadherins; Female; Fertility; Gametogenesis; Germ Cells; Gonads; Humans; Male; Morphogenesis; Reproduction
PubMed: 33158211
DOI: 10.3390/ijms21218264