Exogenous Oestrogen Impacts Cell Fate Decision in the Developing Gonads: A Potential Cause of Declining Human Reproductive Health

Autor: Melanie K Stewart, Deidre M. Mattiske, Andrew J Pask
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Sex Differentiation
Cellular differentiation
Disorders of Sex Development
Review
Endocrine Disruptors
lcsh:Chemistry
Mice
0302 clinical medicine
Pregnancy
Disorders of sex development
lcsh:QH301-705.5
Spectroscopy
fertility
biology
Cell Differentiation
SOX9 Transcription Factor
Anti-Müllerian hormone
General Medicine
Sex reversal
Computer Science Applications
Cell biology
Reproductive Health
medicine.anatomical_structure
Female
Development of the gonads
differences of sexual development
SOX9
endocrine system
Gonad
030209 endocrinology & metabolism
Ovary
Models
Biological
gonad
Catalysis
Inorganic Chemistry
03 medical and health sciences
medicine
Animals
Humans
Physical and Theoretical Chemistry
Gonads
Molecular Biology
Sexual differentiation
Organic Chemistry
Estrogens
Sex Determination Processes
medicine.disease
endocrine disrupting chemicals
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
biology.protein
oestrogen
Zdroj: International Journal of Molecular Sciences, Vol 21, Iss 8377, p 8377 (2020)
International Journal of Molecular Sciences
ISSN: 1422-0067
DOI: 10.3390/ijms21218377
Popis: The increasing incidence of testicular dysgenesis syndrome-related conditions and overall decline in human fertility has been linked to the prevalence of oestrogenic endocrine disrupting chemicals (EDCs) in the environment. Ectopic activation of oestrogen signalling by EDCs in the gonad can impact testis and ovary function and development. Oestrogen is the critical driver of ovarian differentiation in non-mammalian vertebrates, and in its absence a testis will form. In contrast, oestrogen is not required for mammalian ovarian differentiation, but it is essential for its maintenance, illustrating it is necessary for reinforcing ovarian fate. Interestingly, exposure of the bi-potential gonad to exogenous oestrogen can cause XY sex reversal in marsupials and this is mediated by the cytoplasmic retention of the testis-determining factor SOX9 (sex-determining region Y box transcription factor 9). Oestrogen can similarly suppress SOX9 and activate ovarian genes in both humans and mice, demonstrating it plays an essential role in all mammals in mediating gonad somatic cell fate. Here, we review the molecular control of gonad differentiation and explore the mechanisms through which exogenous oestrogen can influence somatic cell fate to disrupt gonad development and function. Understanding these mechanisms is essential for defining the effects of oestrogenic EDCs on the developing gonads and ultimately their impacts on human reproductive health.
Databáze: OpenAIRE
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