API

Event: 1790

Key Event Title

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Increased, Differentiation to Testis

Short name

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Increased, Differentiation to Testis

Biological Context

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Level of Biological Organization
Tissue


Organ term

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Organ term
testis


Key Event Components

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Process Object Action
male gonad development immature gonad increased

Key Event Overview


AOPs Including This Key Event

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Stressors

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Taxonomic Applicability

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Term Scientific Term Evidence Link
Vertebrates Vertebrates Moderate NCBI

Life Stages

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Life stage Evidence
Development Moderate

Sex Applicability

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Term Evidence
Male Moderate

Key Event Description

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Prior to sex determination in many vertebrates, the developing organism have a bipotential gonad that can be fated to either sex depending on the genetic makeup of the embryo (genetic sex determination), environmental conditions (environmental sex determination) or both.Among vertebrates, the primordial gonad and the structural morphology of the testes are highly conserved. 

During male development, the embryonic stem cells can differentiate to primordial germ cells, which in turn proliferate and differentiate into precursor spermatogonia stem cells. Sertoli cells are the first cells to differentiate into the different fetal gonad seminiferous cords surrounded by peritubular myoid cells and enclosing fetal germ cells.  Sertoli cells can also differentiate into leydig cells. Successively, the interstitial Leydig cells differentiate and produce testosterone to induce masculinization (Fisher et al., 2003)

Although the timing and location of gene expression leading to this morphological development of the testis may differ among taxa, many vertebrate taxa share a common set of genes crucial for the testis differentiation pathway to be activated and be maintained. In most mammals, the autosomal gene SOX9 is first upregulated in the precursor Sertoli cells, which are important for proper testicular development and function. SOX9 works with fibroblast growth factor 9 (FGF9) in a feed-forward loop that represses female pathway genes such as the wnt family member 4 WNT4 an in turn maintaining the male pathway. After sex determination has been established, expression of DMRT1 (double- sex and mab-related transcription factor 1) in the developing gonads (during the downstream events of the testicular differentiation pathway) has been linked to proper development and maintenance of male gonads. For birds, it has been confirmed that DMRT1 is the bird sex- determining gene whereas for most mammals, the SRY gene initiates the testis determining molecular cascade (Marshall Graves et al., 2010; Trukhina et al., 2013). 


How It Is Measured or Detected

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Histological examination by light microscopy are performed to identify the phenotypic sex characteristics. In general, phenotypic males in early development will show three main differentiating cell types; the gamete forming cells (spermatogonia), support cells (Sertoli cells) and hormone secreting cells (Leydig or interstitial cells).


Domain of Applicability

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The primordial gonad, the key genes for testicular differentiation and the structural morphology of the testes are highly conserved among vertebrates. Consequentially, this key even is applicable to most vertebrate taxa. 

 


References

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Capel, Blanche. (2017). Vertebrate sex determination: Evolutionary plasticity of a fundamental switch. Nature Reviews Genetics. 18. 10.1038/nrg.2017.60. 

Cutting, A., Chue, J., & Smith, C. A. (2013). Just how conserved is vertebrate sex determination?. Developmental dynamics : an official publication of the American Association of Anatomists, 242(4), 380–387. 

 DeFalco T, Capel B. Gonad morphogenesis in vertebrates: divergent means to a convergent end. Annu Rev Cell Dev Biol. 2009;25:457-482. doi:10.1146/annurev.cellbio.042308.13350

Marshall Graves, J. A., & Peichel, C. L. (2010). Are homologies in vertebrate sex determination due to shared ancestry or to limited options?. Genome biology, 11(4), 205. https://doi.org/10.1186/gb-2010-11-4-205

McLaren A. (1998). Gonad development: assembling the mammalian testis. Current biology : CB8(5), R175–R177. https://doi.org/10.1016/s0960-9822(98)70104-6

Nishimura, T., & Tanaka, M. (2014). Gonadal development in fish. Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation8(5), 252–261. 

Santos, D., Luzio, A., & Coimbra, A. M. (2017). Zebrafish sex differentiation and gonad development: A review on the impact of environmental factors. Aquatic toxicology (Amsterdam, Netherlands)191, 141–163. 

Trukhina, A. V., Lukina, N. A., Wackerow-Kouzova, N. D., & Smirnov, A. F. (2013). The variety of vertebrate mechanisms of sex determination. BioMed research international, 2013, 587460. https://doi.org/10.1155/2013/587460