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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 -
Journal of Neuroscience Research Jan 2017A general theory of mammalian sexual differentiation is proposed. All biological sex differences are the result of the inequality in effects of the sex chromosomes,... (Review)
Review
A general theory of mammalian sexual differentiation is proposed. All biological sex differences are the result of the inequality in effects of the sex chromosomes, which are the only factors that differ in XX vs. XY zygotes. This inequality leads to male-specific effects of the Y chromosome, including expression of the testis-determining gene Sry that causes differentiation of testes. Thus, Sry sets up lifelong sex differences in effects of gonadal hormones. Y genes also act outside of the gonads to cause male-specific effects. Differences in the number of X chromosomes between XX and XY cells cause sex differences in expression (1) of Xist, (2) of X genes that escape inactivation, and (3) of parentally imprinted X genes. Sex differences in phenotype are ultimately the result of multiple, independent sex-biasing factors, hormonal and sex chromosomal. These factors act in parallel and in combination to induce sex differences. They also can offset each other to reduce sex differences. Other mechanisms, operating at the level of populations, cause groups of males to differ on average from groups of females. The theory frames questions for further study, and directs attention to inherent sex-biasing factors that operate in many tissues to cause sex differences, and to cause sex-biased protection from disease. © 2016 Wiley Periodicals, Inc.
Topics: Animals; Genotype; Humans; Phenotype; Sex Characteristics; Sex Chromosomes; Sex Differentiation
PubMed: 27870435
DOI: 10.1002/jnr.23884 -
Endocrinology Sep 2020The organizational/activational hypothesis suggests that gonadal steroid hormones like testosterone (T) and estradiol (E2) are important at 2 different times during the... (Review)
Review
The organizational/activational hypothesis suggests that gonadal steroid hormones like testosterone (T) and estradiol (E2) are important at 2 different times during the lifespan when they perform 2 different functions. First steroids "organize" brain structures early in life and during puberty, and in adults these same hormones "activate" sexually dimorphic behaviors. This hypothesis has been tested and proven valid for a large number of behaviors (learning, memory, social, and sexual behaviors). Sex differences in drug addiction are well established both for humans and animal models. Previous research in this field has focused primarily on cocaine self-administration by rats. Traditionally, observed sex differences have been explained by the sex-specific concentrations of gonadal hormones present at the time of the drug-related behavior. Studies with gonadectomized rodents establishes an activational role for E2 that facilitates vulnerability in females, and when E2 is combined with progesterone, addiction is attenuated. Literature on organizational actions of steroids is sparse but predicts that T, after it is aromatized to E2, changes aspects of the neural reward system. Here we summarize these data and propose that sex chromosome complement also plays a role in determining sex-specific drug-taking behavior. Future research is needed to disentangle the effects of hormones and sex chromosome complement, and we propose the four core genotype mouse model as an effective tool for answering these questions.
Topics: Aging; Animals; Brain; Gonadal Steroid Hormones; Humans; Reward; Risk Factors; Sex Characteristics; Sex Differentiation; Sex Factors; Substance-Related Disorders
PubMed: 32761086
DOI: 10.1210/endocr/bqaa129 -
Sexual Development : Genetics,... 2021The role of environmental factors in sexual differentiation in amphibians is not new. The effect of hormones or hormone-like compounds is widely demonstrated. However,... (Review)
Review
The role of environmental factors in sexual differentiation in amphibians is not new. The effect of hormones or hormone-like compounds is widely demonstrated. However, the effect of temperature has traditionally been regarded as something anecdotal that occurs in extreme situations and not as a factor to be considered. The data currently available reveal a different situation. Sexual differentiation in some amphibian species can be altered even by small changes in temperature. On the other hand, although not proven, it is possible that temperature is related to the appearance of sex-reversed individuals in natural populations under conditions unrelated to environmental contaminants. According to this, temperature, through sex reversal (phenotypic sex opposed to genetic sex), could play an important role in the turnover of sex-determining genes and in the maintenance of homomorphic sex chromosomes in this group. Accordingly, and given the expected increase in global temperatures, growth and sexual differentiation in amphibians could easily be affected, altering the sex ratio in natural populations and posing major conservation challenges for a group in worldwide decline. It is therefore particularly urgent to understand the mechanism by which temperature affects sexual differentiation in amphibians.
Topics: Amphibians; Animals; Humans; Sex Chromosomes; Sex Determination Processes; Sex Differentiation; Temperature
PubMed: 34000727
DOI: 10.1159/000515220 -
Genes Feb 2021Mechanisms underlying sex determination and differentiation in animals are known to encompass a diverse array of molecular clues. Recent innovations in high-throughput... (Review)
Review
Mechanisms underlying sex determination and differentiation in animals are known to encompass a diverse array of molecular clues. Recent innovations in high-throughput sequencing and mass spectrometry technologies have been widely applied in non-model organisms without reference genomes. Crustaceans are no exception. They are particularly diverse among the Arthropoda and contain a wide variety of commercially important fishery species such as shrimps, lobsters and crabs (Order Decapoda), and keystone species of aquatic ecosystems such as water fleas (Order Branchiopoda). In terms of decapod sex determination and differentiation, previous approaches have attempted to elucidate their molecular components, to establish mono-sex breeding technology. Here, we overview reports describing the physiological functions of sex hormones regulating masculinization and feminization, and gene discovery by transcriptomics in decapod species. Moreover, this review summarizes the recent progresses of studies on the juvenile hormone-driven sex determination system of the branchiopod genus , and then compares sex determination and endocrine systems between decapods and branchiopods. This review provides not only substantial insights for aquaculture research, but also the opportunity to re-organize the current and future trends of this field.
Topics: Androgens; Animals; Cladocera; Daphnia; Decapoda; Ecosystem; Endocrine System; Sex Determination Processes; Sex Differentiation; Transcriptome
PubMed: 33669984
DOI: 10.3390/genes12020305 -
Sexual Development : Genetics,... 2021At embryonic day (E) 10.5, prior to gonadal sex determination, XX and XY gonads are bipotential and able to differentiate into either a testis or an ovary. At this... (Review)
Review
At embryonic day (E) 10.5, prior to gonadal sex determination, XX and XY gonads are bipotential and able to differentiate into either a testis or an ovary. At this point, they are transcriptionally and morphologically indistinguishable. Sex determination begins around E11.5 in the mouse when the supporting cell lineage commits to either Sertoli or granulosa cell fate. Testis-specific factors such as SRY and SOX9 drive differentiation of bipotential-supporting cells into the Sertoli cell pathway, whereas ovary-specific factors like WNT4 and FOXL2 guide differentiation into granulosa cells. It is known that these 2 pathways are mutually antagonistic, and repression of the alternative fate is critical for maintenance of the testis or ovary programs. While we understand much about the transcription factor networks guiding the process of sex determination, it is only more recently that we have begun to understand how this process is epigenetically controlled. Studies in the past decade have demonstrated the importance of the chromatin state for gene expression and cell fate commitment, with histone modifications and DNA accessibility having a direct role in gene regulation. It is now clear that the chromatin state during sex determination is dynamic and likely critical for the establishment and/or maintenance of the transcriptional programs. Prior to sex determination, supporting cells have similar chromatin structure and histone modification profiles, reflecting the bipotential nature of these cells. After differentiation to Sertoli or granulosa cells, the chromatin state acquires sex-specific profiles. The proteins that regulate the deposition of histone modifications or the opening of compact chromatin likely play an important role in Sertoli and granulosa cell fate commitment and gonad development. Here, we describe studies profiling the chromatin state during gonadal sex determination and one example in which depletion of Cbx2, a member of the Polycomb Repressive Complex 1 (PRC1), causes male-to-female sex reversal due to a failure to repress the ovarian pathway.
Topics: Animals; Chromatin; Female; Gene Expression Regulation, Developmental; Gonads; Male; Mice; Polycomb Repressive Complex 1; SOX9 Transcription Factor; Sex Determination Processes; Sex Differentiation; Testis
PubMed: 34753132
DOI: 10.1159/000520007 -
Philosophical Transactions of the Royal... Aug 2021So far, very few sex-determining genes have been identified in vertebrates and most of them, the so-called 'usual suspects', evolved from genes which fulfil essential... (Review)
Review
So far, very few sex-determining genes have been identified in vertebrates and most of them, the so-called 'usual suspects', evolved from genes which fulfil essential functions during sexual development and are thus already tightly linked to the process that they now govern. The single exception to this 'usual suspects' rule in vertebrates so far is the conserved salmonid sex-determining gene, (sexually dimorphic on the Y chromosome), that evolved from a gene known to be involved in regulation of the immune response. It is contained in a jumping sex locus that has been transposed or translocated into different ancestral autosomes during the evolution of salmonids. This special feature of , i.e. being inserted in a 'jumping sex locus', could explain how salmonid sex chromosomes remain young and undifferentiated to escape degeneration. Recent knowledge on the mechanism of action of demonstrates that it triggers its sex-determining action by deregulating oestrogen synthesis that is a conserved and crucial pathway for ovarian differentiation in vertebrates. This result suggests that has evolved to cope with a pre-existing sex differentiation regulatory network. Therefore, 'limited options' for the emergence of new master sex-determining genes could be more constrained by their need to tightly interact with a conserved sex differentiation regulatory network rather than by being themselves 'usual suspects', already inside this sex regulatory network. This article is part of the theme issue 'Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part I)'.
Topics: Animals; Salmonidae; Sex Determination Processes; Sex Differentiation
PubMed: 34247499
DOI: 10.1098/rstb.2020.0092 -
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 -
Endocrinology Nov 2021Significant sex differences exist across cellular, tissue organization, and body system scales to serve the distinct sex-specific functions required for reproduction.... (Review)
Review
Significant sex differences exist across cellular, tissue organization, and body system scales to serve the distinct sex-specific functions required for reproduction. They are present in all animals that reproduce sexually and have widespread impacts on normal development, aging, and disease. Observed from the moment of fertilization, sex differences are patterned by sexual differentiation, a lifelong process that involves mechanisms related to sex chromosome complement and the epigenetic and acute activational effects of sex hormones. In this mini-review, we examine evidence for sex differences in cellular responses to DNA damage, their underlying mechanisms, and how they might relate to sex differences in cancer incidence and response to DNA-damaging treatments.
Topics: Adaptation, Physiological; Aging; Animals; DNA Damage; DNA Repair; Female; Gonadal Steroid Hormones; Humans; Male; Sex Characteristics; Sex Differentiation
PubMed: 34478502
DOI: 10.1210/endocr/bqab192 -
International Journal of Molecular... Oct 2022For many decades to date, neuroendocrinologists have delved into the key contribution of gonadal hormones to the generation of sex differences in the developing brain... (Review)
Review
For many decades to date, neuroendocrinologists have delved into the key contribution of gonadal hormones to the generation of sex differences in the developing brain and the expression of sex-specific physiological and behavioral phenotypes in adulthood. However, it was not until recent years that the role of sex chromosomes in the matter started to be seriously explored and unveiled beyond gonadal determination. Now we know that the divergent evolutionary process suffered by X and Y chromosomes has determined that they now encode mostly dissimilar genetic information and are subject to different epigenetic regulations, characteristics that together contribute to generate sex differences between XX and XY cells/individuals from the zygote throughout life. Here we will review and discuss relevant data showing how particular X- and Y-linked genes and epigenetic mechanisms controlling their expression and inheritance are involved, along with or independently of gonadal hormones, in the generation of sex differences in the brain.
Topics: Female; Male; Animals; Sex Differentiation; Y Chromosome; Sex Chromosomes; Sex Characteristics; Gonadal Hormones; Brain; Epigenesis, Genetic; X Chromosome
PubMed: 36293143
DOI: 10.3390/ijms232012288