scholarly journals Signaling Pathways Involved in Mammalian Sex Determination and Gonad Development

2016 ◽  
Vol 9 (6) ◽  
pp. 297-315 ◽  
Author(s):  
Simon P. Windley ◽  
Dagmar Wilhelm
Keyword(s):  
Sex Determination ◽  
Signaling Pathways ◽  
Gonad Development

scholarly journals Single cell transcriptomics reveal temporal dynamics of critical regulators of germ cell fate during mouse sex determination

2019 ◽  
Author(s):  
Chloé Mayère ◽  
Yasmine Neirijnck ◽  
Pauline Sararols ◽  
Chris M Rands ◽  
Isabelle Stévant ◽  
...  
Keyword(s):  
Sex Determination ◽  
Germ Cell ◽  
Single Cell ◽  
Cell Fate ◽  
Gene Networks ◽  
Network Inference ◽  
Temporal Dynamics ◽  
Intron Retention ◽  
Gonad Development ◽  
Altered Expression

SummaryDespite the importance of germ cell (GC) differentiation for sexual reproduction, the gene networks underlying their fate remain unclear. Here, we comprehensively characterize the gene expression dynamics during sex determination based on single-cell RNA sequencing of 14,914 XX and XY mouse GCs between embryonic days (E) 9.0 and 16.5. We found that XX and XY GCs diverge transcriptionally as early as E11.5 with upregulation of genes downstream of the Bone morphogenic protein (BMP) and Nodal/Activin pathways in XY and XX GCs, respectively. We also identified a sex-specific upregulation of genes associated with negative regulation of mRNA processing and an increase in intron retention consistent with a reduction in mRNA splicing in XY testicular GCs by E13.5. Using computational gene regulation network inference analysis, we identified sex-specific, sequential waves of putative key regulator genes during GC differentiation and revealed that the meiotic genes are regulated by positive and negative master modules acting in an antagonistic fashion. Finally, we found that rare adrenal GCs enter meiosis similarly to ovarian GCs but display altered expression of master genes controlling the female and male genetic programs, indicating that the somatic environment is important for GC function. Our data is available on a web platform and provides a molecular roadmap of GC sex determination at single-cell resolution, which will serve as a valuable resource for future studies of gonad development, function and disease.

scholarly journals Vertebrate sex determination: many means to an end

Reproduction ◽  
2002 ◽  
pp. 447-457 ◽  
Author(s):  
BC Morrish ◽  
AH Sinclair
Keyword(s):  
Sex Determination ◽  
Regulatory Network ◽  
Gonadal Dysgenesis ◽  
Developmental Process ◽  
Gonad Development ◽  
Complex Interplay ◽  
Specific Expression ◽  
Sex Specificity ◽  
Bipotential Gonad

The differentiation of a testis or ovary from a bipotential gonadal primordium is a developmental process common to mammals, birds and reptiles. Since the discovery of SRY, the Y-linked testis-determining gene in mammals, extensive efforts have failed to find its orthologue in other vertebrates, indicating evolutionary plasticity in the switch that triggers sex determination. Several other genes are known to be important for sex determination in mammals, such as SOX9, AMH, WT1, SF1, DAX1 and DMRT1. Analyses of these genes in humans with gonadal dysgenesis, mouse models and using in vitro cell culture assays have revealed that sex determination results from a complex interplay between the genes in this network. All of these genes are conserved in other vertebrates, such as chickens and alligators, and show gonad-specific expression in these species during the period of sex determination. Intriguingly, the sequence, sex specificity and timing of expression of some of these genes during sex determination differ among species. This finding indicates that the interplay between genes in the regulatory network leading to gonad development differs between vertebrates. However, despite this, the development of a testis or ovary from a bipotential gonad is remarkably similar across vertebrates.

scholarly journals Divergent Expression Regulation of Gonad Development Genes in Medaka Shows Incomplete Conservation of the Downstream Regulatory Network of Vertebrate Sex Determination

2013 ◽  
Vol 30 (10) ◽  
pp. 2328-2346 ◽  
Author(s):  
Amaury Herpin ◽  
Mateus C. Adolfi ◽  
Barbara Nicol ◽  
Maria Hinzmann ◽  
Cornelia Schmidt ◽  
...  
Keyword(s):  
Sex Determination ◽  
Regulatory Network ◽  
Gonad Development ◽  
Expression Regulation

scholarly journals The Chromatin State during Gonadal Sex Determination

2021 ◽  
pp. 1-9
Author(s):  
Shannon Dupont ◽  
Blanche Capel
Keyword(s):  
Sex Determination ◽  
Cell Fate ◽  
Granulosa Cell ◽  
Histone Modifications ◽  
Granulosa Cells ◽  
Gonad Development ◽  
Chromatin State ◽  
Supporting Cells ◽  
Direct Role ◽  
Specific Factors

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 <i>Cbx2</i>, a member of the Polycomb Repressive Complex 1 (PRC1), causes male-to-female sex reversal due to a failure to repress the ovarian pathway.

scholarly journals Molecular mechanisms involved in mammalian primary sex determination

2014 ◽  
Vol 53 (1) ◽  
pp. R21-R37 ◽  
Author(s):  
Zhen-Yu She ◽  
Wan-Xi Yang
Keyword(s):  
Sex Determination ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Genital Ridge ◽  
Genetic Studies ◽  
Delicate Balance ◽  
Developmental Decision

Sex determination refers to the developmental decision that directs the bipotential genital ridge to develop as a testis or an ovary. Genetic studies on mice and humans have led to crucial advances in understanding the molecular fundamentals of sex determination and the mutually antagonistic signaling pathway. In this review, we summarize the current molecular mechanisms of sex determination by focusing on the known critical sex determining genes and their related signaling pathways in mammalian vertebrates from mice to humans. We also discuss the underlying delicate balance between testis and ovary sex determination pathways, concentrating on the antagonisms between major sex determining genes.

scholarly journals Demographic and genetic consequences of disturbed sex determination

2017 ◽  
Vol 372 (1729) ◽  
pp. 20160326 ◽  
Author(s):  
Claus Wedekind
Keyword(s):  
Population Growth ◽  
Sex Determination ◽  
Sex Ratios ◽  
Natural Populations ◽  
Gonad Development ◽  
Empirical Work ◽  
Sex Reversal ◽  
Negative Effects ◽  
Population Extinction

During sex determination, genetic and/or environmental factors determine the cascade of processes of gonad development. Many organisms, therefore, have a developmental window in which their sex determination can be sensitive to, for example, unusual temperatures or chemical pollutants. Disturbed environments can distort population sex ratios and may even cause sex reversal in species with genetic sex determination. The resulting genotype–phenotype mismatches can have long-lasting effects on population demography and genetics. I review the theoretical and empirical work in this context and explore in a simple population model the role of the fitness v yy of chromosomally aberrant YY genotypes that are a consequence of environmentally induced feminization. Low v yy is mostly beneficial for population growth. During feminization, low v yy reduces the proportion of genetic males and hence accelerates population growth, especially at low rates of feminization and at high fitness costs of the feminization itself (i.e. when feminization would otherwise not affect population dynamics much). When sex reversal ceases, low v yy mitigates the negative effects of feminization and can even prevent population extinction. Little is known about v yy in natural populations. The available models now need to be parametrized in order to better predict the long-term consequences of disturbed sex determination. This article is part of the themed issue ‘Adult sex ratios and reproductive decisions: a critical re-examination of sex differences in human and animal societies’.

scholarly journals MicroRNAs in amniotic fluid and maternal blood plasma associated with sex determination and early gonad differentiation in cattle

2021 ◽  
Author(s):  
José María Sánchez ◽  
Isabel Gómez-Redondo ◽  
John A Browne ◽  
Benjamín Planells ◽  
Alfonso Gutiérrez-Adán ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Sex Determination ◽  
Blood Plasma ◽  
Critical Role ◽  
Gonad Development ◽  
Maternal Blood ◽  
Female Embryo ◽  
Single Male ◽  
Male Embryo ◽  
Gonad Differentiation

Abstract MicroRNAs (miRNAs), as gene expression regulators, may play a critical role during the sex determination process. We hypothesised that the expression of miRNAs in amniotic fluid (AF) and maternal blood plasma (MP) during this process would be affected by the sex of the embryo. Amniotic fluid and MP were collected from six pregnant heifers (3 carrying a single male and 3 a single female embryo) following slaughter on Day 39 post insemination, coinciding with the peak of SRY expression. Samples (6 AF and 6 MP) were profiled using a miRNA Serum/Plasma Focus PCR Panel. Differentially expressed (DE) miRNAs were identified in AF (n = 5) and associated MP (n = 56) of male vs female embryos (P &lt; 0.05). Functional analysis showed that inflammatory and immune response were amongst the 13 biological processes enriched by miRNAs DE in MP in the male group (FDR &lt; 0.05), suggesting that these sex-dependent DE miRNAs may be implicated in modulating the receptivity of the dam to a male embryo. Further, we compared the downstream targets of the sex-dependent DE miRNAs detected in MP with genes previously identified as DE in male vs female genital ridges. The analyses revealed potential targets that might be important during this developmental stage such as SHROOM2, DDX3Y, SOX9, SRY, PPP1CB, JARID2, USP9X, KDM6A, and EIF2S3. Results from this study highlight novel aspects of sex determination and embryo-maternal communication in cattle such as the potential role of miRNAs in gonad development as well as in the modulation of the receptivity of the dam to a male embryo.

scholarly journals Role of Alternative Splicing in Sex Determination in Vertebrates

2021 ◽  
pp. 1-11
Author(s):  
Isabel Gómez-Redondo ◽  
Benjamín Planells ◽  
Paula Navarrete ◽  
Alfonso Gutiérrez-Adán
Keyword(s):  
Alternative Splicing ◽  
Sex Determination ◽  
Transcription Initiation ◽  
Time Window ◽  
Gonad Development ◽  
Reproductive Organ ◽  
Mrna Splicing ◽  
Transcriptional Level ◽  
Splicing Regulators

During the process of sex determination, a germ-cell-containing undifferentiated gonad is converted into either a male or a female reproductive organ. Both the composition of sex chromosomes and the environment determine sex in vertebrates. It is assumed that transcription level regulation drives this cascade of mechanisms; however, transcription factors can alter gene expression beyond transcription initiation by controlling pre-mRNA splicing and thereby mRNA isoform production. Using the key time window in sex determination and gonad development in mice, it has been reported that new non-transcriptional events, such as alternative splicing, could play a key role in sex determination in mammals. We know the role of key regulatory factors, like WT1(+/–KTS) or FGFR2(b/c) in pre-mRNA splicing and sex determination, indicating that important steps in the vertebrate sex determination process probably operate at a post-transcriptional level. Here, we discuss the role of pre-mRNA splicing regulators in sex determination in vertebrates, focusing on the new RNA-seq data reported from mice fetal gonadal transcriptome.

scholarly journals The germline-specific region of the sea lamprey genome plays a key role in spermatogenesis

2021 ◽  
Author(s):  
Tamanna Yasmin ◽  
Phil Grayson ◽  
Margaret F. Docker ◽  
Sara V. Good
Keyword(s):  
Sex Determination ◽  
Genome Rearrangement ◽  
De Novo ◽  
Sequence Data ◽  
Gonad Development ◽  
Sea Lamprey ◽  
Specific Region ◽  
A Genome ◽  
Reproductive Processes

The sea lamprey genome undergoes programmed genome rearrangement (PGR) in which ~20% is jettisoned from somatic cells soon after fertilization. Although the role of PGR in embryonic development has been studied, the role of the germline-specific region (GSR) in gonad development is unknown. We analysed RNA-sequence data from 28 sea lamprey gonads sampled across life-history stages, generated a genome-guided de novo superTransciptome with annotations, and identified genes in the GSR. We found that the 638 genes in the GSR are enriched for reproductive processes, exhibit 36x greater odds of being expressed in testes than ovaries, show little evidence of conserved synteny with other chordates, and most have putative paralogues in the GSR and/or somatic genomes. Further, several of these genes play known roles in sex determination and differentiation in other vertebrates. We conclude that the GSR of sea lamprey plays an important role in testicular differentiation and potentially sex determination.

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