Event: 1789

Key Event Title


Reduction, 17beta-estradiol synthesis by the undifferentiated gonad

Short name


Reduction, E2 Synthesis by the undifferentiated gonad

Biological Context


Level of Biological Organization

Cell term


Cell term
primordial germ cell

Organ term


Organ term

Key Event Components


Process Object Action
estrogen biosynthetic process 17beta-estradiol decreased

Key Event Overview

AOPs Including This Key Event




Taxonomic Applicability


Term Scientific Term Evidence Link
Vertebrates Vertebrates Moderate NCBI

Life Stages


Life stage Evidence
Development Moderate

Sex Applicability


Term Evidence
Unspecific Low

Key Event Description


Estrogens are essential for normal ovarian differentiation, growth and maintenance. When estrogens bind to estrogen receptors (ER), these then regulate the transcription of downstream estrogen-responsive genes necessary for proper gonad development (Guiguen et al., 2010; Gorelick et al., 2011). Among the different forms of estrogens, 17β-estradiol (estradiol) is considered the most fundamental in gonad differentiation in most vertebrates, as it is responsible for inducing and maintaining ovarian development(Bondesson et al., 2015; Li et al., 2019). Conversely, disruption of the E2 synthesis by the undifferentiated gonad has been linked to altered gonad differentiation and development in many vertebrates. 

How It Is Measured or Detected


Domain of Applicability


Most of the key enzymes involved in the process of estradiol biosynthesis are all well conserved among vertebrates (Callard et al., 2001; Thornton et al., 2001; Eick et al., 2011; Coumailleau et al., 2015). Estrogens play a key role in embryonic development particularly during gonadogenesis for most vertebrates (Coumailleauet al., 2015; Callard et al., 2015). Therefore, it is possible that this key event is applicable to most vertebrate taxa. In contrast, this key event is not applicable to organisms that lack the necessary enzymes for estrogen synthesis such as invertebrates (Jones et al., 2017). 



Bondesson, M., Hao, R., Lin, C. Y., Williams, C., & Gustafsson, J. Å. (2015). Estrogen receptor signaling during vertebrate development. Biochimica et biophysica acta, 1849(2), 142–151. 

Callard, G. V., Tarrant, A. M., Novillo, A., Yacci, P., Ciaccia, L., Vajda, S., Chuang, G. Y., Kozakov, D., Greytak, S. R., Sawyer, S., Hoover, C., & Cotter, K. A. (2011). Evolutionary origins of the estrogen signaling system: insights from amphioxus. The Journal of steroid biochemistry and molecular biology, 127(3-5), 176–188. 

Cheshenko, K., Pakdel, F., Segner, H., Kah, O., & Eggen, R. I. (2008). Interference of endocrine disrupting chemicals with aromatase CYP19 expression or activity, and consequences for reproduction of teleost fish. General and comparative endocrinology155(1), 31–62. 

Coumailleau, P., Pellegrini, E., Adrio, F., Diotel, N., Cano-Nicolau, J., Nasri, A., Vaillant, C., & Kah, O. (2015). Aromatase, estrogen receptors and brain development in fish and amphibians. Biochimica et biophysica acta1849(2), 152–162. 

Eick, G. N., & Thornton, J. W. (2011). Evolution of steroid receptors from an estrogen-sensitive ancestral receptor. Molecular and cellular endocrinology, 334(1-2), 31–38. 

Gorelick, D. A., & Halpern, M. E. (2011). Visualization of estrogen receptor transcriptional activation in zebrafish. Endocrinology, 152(7), 2690–2703. https://doi.org/10.1210/en.2010-1257

Guiguen, Y., Fostier, A., Piferrer, F., & Chang, C. F. (2010). Ovarian aromatase and estrogens: a pivotal role for gonadal sex differentiation and sex change in fish. General and comparative endocrinology165(3), 352–366. 

Jones, B. L., Walker, C., Azizi, B., Tolbert, L., Williams, L. D., & Snell, T. W. (2017). Conservation of estrogen receptor function in invertebrate reproduction. BMC evolutionary biology, 17(1), 65. 

Li, M., Sun, L., & Wang, D. (2019). Roles of estrogens in fish sexual plasticity and sex differentiation. General and comparative endocrinology277, 9–16. https://doi.org/10.1016/j.ygcen.2018.11.015

Ruksana, S., Pandit, N. P., & Nakamura, M. (2010). Efficacy of exemestane, a new generation of aromatase inhibitor, on sex differentiation in a gonochoristic fish. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 152(1), 69–74. 

Schroeder, A. L., Ankley, G. T., Habib, T., Garcia-Reyero, N., Escalon, B. L., Jensen, K. M., Kahl, M. D., Durhan, E. J., Makynen, E. A., Cavallin, J. E., Martinovic-Weigelt, D., Perkins, E. J., & Villeneuve, D. L. (2017). Rapid effects of the aromatase inhibitor fadrozole on steroid production and gene expression in the ovary of female fathead minnows (Pimephales promelas). General and comparative endocrinology, 252, 79–87. 

Thornton J. W. (2001). Evolution of vertebrate steroid receptors from an ancestral estrogen receptor by ligand exploitation and serial genome expansions. Proceedings of the National Academy of Sciences of the United States of America, 98(10), 5671–5676. 

Warner, D. A., Addis, E., Du, W. G., Wibbels, T., & Janzen, F. J. (2014). Exogenous application of estradiol to eggs unexpectedly induces male development in two turtle species with temperature-dependent sex determination. General and comparative endocrinology206, 16–23. 

Yin, Y., Tang, H., Liu, Y., Chen, Y., Li, G., Liu, X., & Lin, H. (2017). Targeted Disruption of Aromatase Reveals Dual Functions of cyp19a1a During Sex Differentiation in Zebrafish. Endocrinology158(9), 3030–3041.