Journal
DIFFERENTIATION
Volume 118, Issue -, Pages 41-71Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.diff.2020.11.004
Keywords
Estrogen; Estrogen receptor; Development; Differentiation; Fetal; Neonatal; Male reproduction; Testis; Rete testis; Efferent ductule; Epididymis; Vas deferens; Mesonephros; Mesonephric tubule; Wolffian duct; Rete cord; Environmental estrogens; Testicular dysgenesis syndrome
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Funding
- Eunice Shriver National Institutes of Child Health and Human Development Grant, USA [HD093703]
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Estrogen's role in the male reproductive system has long been underestimated, but it is synthesized in the testes and plays a crucial role in the development and function of the male reproductive system. The balance between male estrogen and androgen is essential for the development of the male reproductive tract.
Estrogen has always been considered the female hormone and testosterone the male hormone. However, estrogen?s presence in the testis and deleterious effects of estrogen treatment during development have been known for nearly 90 years, long before estrogen receptors (ESRs) were discovered. Eventually it was learned that testes actually synthesize high levels of estradiol (E2) and sequester high concentrations in the reproductive tract lumen, which seems contradictory to the overwhelming number of studies showing reproductive pathology following exogenous estrogen exposures. For too long, the developmental pathology of estrogen has dominated our thinking, even resulting in the ?estrogen hypothesis? as related to the testicular dysgenesis syndrome. However, these early studies and the development of an Esr1 knockout mouse led to a deluge of research into estrogen?s potential role in and disruption of development and function of the male reproductive system. What is new is that estrogen action in the male cannot be divorced from that of androgen. This paper presents what is known about components of the estrogen pathway, including its synthesis and target receptors, and the need to achieve a balance between androgen- and estrogen-action in male reproductive tract differentiation and adult functions. The review focuses on what is known regarding development of the male reproductive tract, from the rete testis to the vas deferens, and examines the expression of estrogen receptors and presence of aromatase in the male reproductive system, traces the evidence provided by estrogen-associated knockout and transgenic animal models and discusses the effects of fetal and postnatal exposures to estrogens. Hopefully, there will be enough here to stimulate discussions and new investigations of the androgen:estrogen balance that seems to be essential for development of the male reproductive tract.
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