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Physiological Reviews Jul 2021A diverse array of sex determination () mechanisms, encompassing environmental to genetic, have been found to exist among vertebrates, covering a spectrum from fixed... (Review)
Review
A diverse array of sex determination () mechanisms, encompassing environmental to genetic, have been found to exist among vertebrates, covering a spectrum from fixed mechanisms (mammals) to functional sex change in fishes (sequential hermaphroditic fishes). A major landmark in vertebrate was the discovery of the gene in 1990. Since that time, many attempts to clone an ortholog from nonmammalian vertebrates remained unsuccessful, until 2002, when was discovered as the gene of a small fish, medaka. Surprisingly, however, was found in only 2 species among more than 20 species of medaka, suggesting a large diversity of genes among vertebrates. Considerable progress has been made over the last 3 decades, such that it is now possible to formulate reasonable paradigms of how and gonadal sex differentiation may work in some model vertebrate species. This review outlines our current understanding of vertebrate and gonadal sex differentiation, with a focus on the molecular and cellular mechanisms involved. An impressive number of genes and factors have been discovered that play important roles in testicular and ovarian differentiation. An antagonism between the male and female pathway genes exists in gonads during both sex differentiation and, surprisingly, even as adults, suggesting that, in addition to sex-changing fishes, gonochoristic vertebrates including mice maintain some degree of gonadal sexual plasticity into adulthood. Importantly, a review of various mechanisms among vertebrates suggests that this is the ideal biological event that can make us understand the evolutionary conundrums underlying speciation and species diversity.
Topics: Animals; Female; Gonads; Male; Sex Determination Processes; Sex Differentiation; Vertebrates
PubMed: 33180655
DOI: 10.1152/physrev.00044.2019 -
Sexual Development : Genetics,... 2021Animals determine their sex genetically (GSD: genetic sex determination) and/or environmentally (ESD: environmental sex determination). Medaka (Oryzias latipes) employ a... (Review)
Review
Animals determine their sex genetically (GSD: genetic sex determination) and/or environmentally (ESD: environmental sex determination). Medaka (Oryzias latipes) employ a XX/XY GSD system, however, they display female-to-male sex reversal in response to various environmental changes such as temperature, hypoxia, and green light. Interestingly, we found that 5 days of starvation during sex differentiation caused female-to-male sex reversal. In this situation, the metabolism of pantothenate and fatty acid synthesis plays an important role in sex reversal. Metabolism is associated with other biological factors such as germ cells, HPG axis, lipids, and epigenetics, and supplys substances and acts as signal transducers. In this review, we discuss the importance of metabolism during sex differentiation and how metabolism contributes to sex differentiation.
Topics: Animals; Female; Germ Cells; Male; Oryzias; Sex Determination Analysis; Sex Determination Processes; Sex Differentiation
PubMed: 34284403
DOI: 10.1159/000515281 -
Genes, Brain, and Behavior Feb 2020
Topics: Adaptation, Biological; Animals; Biological Evolution; Evolution, Molecular; Female; Humans; Male; Sex Characteristics; Sex Differentiation
PubMed: 32017390
DOI: 10.1111/gbb.12642 -
International Journal of Molecular... Nov 2022In most mammals, the sex of the gonads is based on the fate of the supporting cell lineages, which arises from the proliferation of coelomic epithelium (CE) that... (Review)
Review
In most mammals, the sex of the gonads is based on the fate of the supporting cell lineages, which arises from the proliferation of coelomic epithelium (CE) that surfaces on the bipotential genital ridge in both XY and XX embryos. Recent genetic studies and single-cell transcriptome analyses in mice have revealed the cellular and molecular events in the two-wave proliferation of the CE that produce the supporting cells. This proliferation contributes to the formation of the primary sex cords in the medullary region of both the testis and the ovary at the early phase of gonadal sex differentiation, as well as to that of the secondary sex cords in the cortical region of the ovary at the perinatal stage. To support gametogenesis, the testis forms seminiferous tubules in the medullary region, whereas the ovary forms follicles mainly in the cortical region. The medullary region in the ovary exhibits morphological and functional diversity among mammalian species that ranges from ovary-like to testis-like characteristics. This review focuses on the mechanism of gonadal sex differentiation along the cortical-medullary axis and compares the features of the cortical and medullary regions of the ovary in mammalian species.
Topics: Male; Female; Mice; Animals; Sex Differentiation; Ovary; Gonads; Testis; Organogenesis; Mammals
PubMed: 36362161
DOI: 10.3390/ijms232113373 -
Endocrinology Aug 2001Mammalian sex differentiation is a hormone-dependent process in the male following the determination of a testis from the indifferent gonad through a cascade of genetic... (Review)
Review
Mammalian sex differentiation is a hormone-dependent process in the male following the determination of a testis from the indifferent gonad through a cascade of genetic events. Female sex differentiation is not dependent on ovarian hormones, yet there is evidence that members of the Wnt family of developmental signaling molecules play a role in Müllerian duct development and in suppressing Leydig cell differentiation in the ovary. The testis induces male sex differentiation (including testis descent) through a time-dependent production of optimal concentrations of anti-Müllerian hormone, insulin-like factor(s) and androgens. Observations in several human syndromes of disordered fetal sex development corroborate findings in murine embryo studies, although there are exceptions in some gene knockout models. The ubiquitously expressed AR interacts in a ligand-dependent manner with coregulators to control the expression of androgen-responsive genes. Preliminary studies suggest the possibility of hormone resistance syndromes associated with coregulator dysfunction. Polymorphic variants in genes controlling androgen synthesis and action may modulate androgenic effects on sex differentiation.
Topics: Androgens; Animals; Humans; Polymorphism, Genetic; Sex Differentiation
PubMed: 11459768
DOI: 10.1210/endo.142.8.8406 -
Yi Chuan = Hereditas Jun 2017The mechanisms of sex determination and differentiation in fish are highly divergent with a broad range of gonadal differentiation types from hermaphroditism to... (Review)
Review
The mechanisms of sex determination and differentiation in fish are highly divergent with a broad range of gonadal differentiation types from hermaphroditism to gonochorism. Multiple triggers regulate the process of sexual differentiation including genetic or environmental factors (temperature, light, hormones and/or pH value, etc.). In recent years, with the advances of molecular technologies and genetic engineering approaches, there are significant breakthroughs in identifying the master genes of vertebrate sex determination and differentiation. In this review, we explore the fundamental and molecular mechanisms underlying the sexual differentiation in teleost fish, using medaka (Oryzias latipes) as a model. We focus on the male pathways and factors, particularly on dmrt1, gsdf and amh genes involved in testicular differentiation, sexual reversal and plasticity. It is anticipated that new techniques will likely be developed in the field of sex manipulations and monosex breeding for fish aquaculture in the future.
Topics: Animals; Oryzias; Sex Determination Processes; Sex Differentiation
PubMed: 28903904
DOI: 10.16288/j.yczz.17-140 -
General and Comparative Endocrinology Nov 2021The involvement of sex steroids in sex determination and differentiation is relatively conserved among non-mammalian vertebrates, especially in fish. Thanks to the... (Review)
Review
The involvement of sex steroids in sex determination and differentiation is relatively conserved among non-mammalian vertebrates, especially in fish. Thanks to the advances in genome sequencing and genome editing, significant progresses have been made in the understanding of steroidogenic pathway and hormonal regulation of sex determination and differentiation in fish. It seems that loss of function study of single gene challenges the traditional views that estrogen is required for ovarian differentiation and androgen is needed for testicular development, but it is not so in essence. Steroidogenic enzymes can be classified into two categories based on expression and enzyme activities in fish. One type, encoded by star2, cyp17a1 and cyp19a1a, is involved in estrogen production and exclusively expressed in the gonads. Mutation of these genes results in the up-regulation of male pathway genes and sex reversal from genetic female to male. The other type, encoded by the duplicated paralogs of the above genes, including star1, cyp11a1, cyp17a2 and cyp19a1b, as well as cyp11c1 gene, is dominantly expressed both in gonads and extra-gonadal tissues. Mutation of these genes alters the steroids (androgen, DHP and cortisol) production and spermatogenesis, fertility, secondary sexual characteristics and sexual behavior, but usually does not affect the sex differentiation. For the estrogen receptors (esr1, esr2a and esr2b), single mutation failed to, but double and triple mutation leads to sex reversal from female to male, indicating that at least Esr2a and Esr2b are required to mediate the role of estrogen in sex determination proved by gene editing experiments. Taken together, results from gene editing enrich our understanding of steroid synthesis pathways and further confirm the critical role of estrogen in female sex determination by antagonizing the male pathway in fish.
Topics: Animals; Female; Fishes; Gene Editing; Gonadal Steroid Hormones; Gonads; Male; Sex Differentiation
PubMed: 34454946
DOI: 10.1016/j.ygcen.2021.113893 -
The New England Journal of Medicine Jan 2004
Review
Topics: Adrenal Hyperplasia, Congenital; Disorders of Sex Development; Female; Genes, Homeobox; Germ Cells; Gonadal Dysgenesis; Humans; Male; Mullerian Ducts; Mutation; Sex Determination Processes; Sex Differentiation
PubMed: 14736929
DOI: 10.1056/NEJMra022784 -
General and Comparative Endocrinology Jun 2019Fish sex could be reversed at the undifferentiated stage of gonad by administration of exogenous estrogen (E2) or blockade of endogenous estrogen synthesis with... (Review)
Review
Fish sex could be reversed at the undifferentiated stage of gonad by administration of exogenous estrogen (E2) or blockade of endogenous estrogen synthesis with aromatase inhibitors, which is designated as primary sex reversal (PSR). Recent studies have well demonstrated that gonochoristic fish maintain their sexual plasticity after sex determination/differentiation. The differentiated ovary could be transdifferentiated into functional testis, and vice versa, the differentiated testis could be transdifferentiated into ovary. By analyzing these two secondary sex reversal (SSR) models, it was found that induction of male-to-female sex reversal initiates from dorsal (near the blood vessel) to the ventral, while induction of female-to-male sex reversal initiates from the ventral to dorsal. Down regulation of endogenous estrogen is the prerequisite for the ovarian transdifferentiation. However, exogenous estrogen alone is not sufficient for inducing differentiated testis to ovary. Administration of E2 and simultaneous blockage of androgen synthesis could induce testicular transdifferentiation. Therefore, endogenous estrogen is critical for the ovarian differentiation/maintenance and androgen is critical for testicular maintenance. Recently, genetic studies with genome editing technologies also showed that disruption of Cyp19a1a induced testicular development, indicating that cyp19a1a is the key gene essential for estrogen synthesis and ovary differentiation/maintenance. Knockout of male pathway genes or overexpression of female pathway genes could up-regulate cyp19a1a expression and increase estrogen level so as to promote ovary. Conversely, knockout of female pathway genes or overexpression of male pathway genes could down-regulate cyp19a1a expression and decrease estrogen level so as to promote testis (transgenic or knockout sex reversal, TSR). Epigenetic regulation of cyp19a1a play a critical role in natural sex reversal (NSR), but its relation with PSR, SSR and TSR needs further detailed investigations. In all, these studies further highlighted the important roles of endogenous estrogens in fish sex differentiation/maintenance.
Topics: Animals; Epigenesis, Genetic; Estrogens; Female; Fishes; Male; Models, Biological; Sex Characteristics; Sex Differentiation
PubMed: 30500373
DOI: 10.1016/j.ygcen.2018.11.015 -
Frontiers in Endocrinology 2020The androgenic gland (AG)-a unique crustacean endocrine organ that secretes factors such as the insulin-like androgenic gland (IAG) hormone-is a key player in crustacean... (Review)
Review
The androgenic gland (AG)-a unique crustacean endocrine organ that secretes factors such as the insulin-like androgenic gland (IAG) hormone-is a key player in crustacean sex differentiation processes. IAG expression induces masculinization, while the absence of the AG or a deficiency in IAG expression results in feminization. Therefore, by virtue of its universal role as a master regulator of crustacean sexual development, the IAG hormone may be regarded as the sexual "IAG-switch." The switch functions within an endocrine axis governed by neuropeptides secreted from the eyestalks, and interacts downstream with specific insulin receptors at its target organs. In recent years, IAG hormones have been found-and sequenced-in dozens of decapod crustacean species, including crabs, prawns, crayfish and shrimps, bearing different types of reproductive strategies-from gonochorism, through hermaphroditism and intersexuality, to parthenogenesis. The IAG-switch has thus been the focus of efforts to manipulate sex developmental processes in crustaceans. Most sex manipulations were performed using AG ablation or knock-down of the gene in males in order to sex reverse them into "neo-females," or using AG implantation/injecting AG extracts or cells into females to produce "neo-males." These manipulations have highlighted the striking crustacean sexual plasticity in different species and have permitted the manifestation of either maleness or femaleness without altering the genotype of the animals. Furthermore, these sex manipulations have not only facilitated fundamental studies of crustacean sexual mechanisms, but have also enabled the development of the first IAG-switch-based monosex population biotechnologies, primarily for aquaculture but also for pest control. Here, we review the crustacean IAG-switch, a unique crustacean endocrine mechanism, from the early discoveries of the AG and the IAG hormone to recent IAG-switch-based manipulations. Moreover, we discuss this unique early pancrustacean insulin-based sexual differentiation control mechanism in contrast to the extensively studied mechanisms in vertebrates, which are based on sex steroids.
Topics: Animals; Arthropod Proteins; Decapoda; Endocrine System; Insulin; Invertebrate Hormones; Sex Differentiation; Signal Transduction
PubMed: 33013714
DOI: 10.3389/fendo.2020.00651