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      Of Oestrogens and Sperm: A Review of the Roles of Oestrogens and Oestrogen Receptors in Male Reproduction

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          Abstract

          The crucial role that oestrogens play in male reproduction has been generally accepted; however, the exact mechanism of their action is not entirely clear and there is still much more to be clarified. The oestrogen response is mediated through oestrogen receptors, as well as classical oestrogen receptors’ variants, and their specific co-expression plays a critical role. The importance of oestrogen signalling in male fertility is indicated by the adverse effects of selected oestrogen-like compounds, and their interaction with oestrogen receptors was proven to cause pathologies. The aims of this review are to summarise the current knowledge on oestrogen signalling during spermatogenesis and sperm maturation and discuss the available information on oestrogen receptors and their splice variants. An overview is given of species-specific differences including in humans, along with a detailed summary of the methodology outcome, including all the genetically manipulated models available to date. This review provides coherent information on the recently discovered mechanisms of oestrogens’ and oestrogen receptors’ effects and action in both testicular somatic and germ cells, as well as in mature sperm, available for mammals, including humans.

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          Most cited references184

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          Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene.

          Estrogen receptor and its ligand, estradiol, have long been thought to be essential for survival, fertility, and female sexual differentiation and development. Consistent with this proposed crucial role, no human estrogen receptor gene mutations are known, unlike the androgen receptor, where many loss of function mutations have been found. We have generated mutant mice lacking responsiveness to estradiol by disrupting the estrogen receptor gene by gene targeting. Both male and female animals survive to adulthood with normal gross external phenotypes. Females are infertile; males have a decreased fertility. Females have hypoplastic uteri and hyperemic ovaries with no detectable corpora lutea. In adult wild-type and heterozygous females, 3-day estradiol treatment at 40 micrograms/kg stimulates a 3- to 4-fold increase in uterine wet weight and alters vaginal cornification, but the uteri and vagina do not respond in the animals with the estrogen receptor gene disruption. Prenatal male and female reproductive tract development can therefore occur in the absence of estradiol receptor-mediated responsiveness.
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            Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase.

            The medicinal properties of marijuana have been recognized for centuries, but clinical and societal acceptance of this drug of abuse as a potential therapeutic agent remains fiercely debated. An attractive alternative to marijuana-based therapeutics would be to target the molecular pathways that mediate the effects of this drug. To date, these neural signaling pathways have been shown to comprise a cannabinoid receptor (CB(1)) that binds the active constituent of marijuana, tetrahydrocannabinol (THC), and a postulated endogenous CB(1) ligand anandamide. Although anandamide binds and activates the CB(1) receptor in vitro, this compound induces only weak and transient cannabinoid behavioral effects in vivo, possibly a result of its rapid catabolism. Here we show that mice lacking the enzyme fatty acid amide hydrolase (FAAH(-/-)) are severely impaired in their ability to degrade anandamide and when treated with this compound, exhibit an array of intense CB(1)-dependent behavioral responses, including hypomotility, analgesia, catalepsy, and hypothermia. FAAH(-/-)-mice possess 15-fold augmented endogenous brain levels of anandamide and display reduced pain sensation that is reversed by the CB(1) antagonist SR141716A. Collectively, these results indicate that FAAH is a key regulator of anandamide signaling in vivo, setting an endogenous cannabinoid tone that modulates pain perception. FAAH may therefore represent an attractive pharmaceutical target for the treatment of pain and neuropsychiatric disorders.
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              Estrogen receptors alpha (ERα) and beta (ERβ): subtype-selective ligands and clinical potential.

              Estrogen receptors alpha (ERα) and beta (ERβ) are nuclear transcription factors that are involved in the regulation of many complex physiological processes in humans. Modulation of these receptors by prospective therapeutic agents is currently being considered for prevention and treatment of a wide variety of pathological conditions, such as, cancer, metabolic and cardiovascular diseases, neurodegeneration, inflammation, and osteoporosis. This review provides an overview and update of compounds that have been recently reported as modulators of ERs, with a particular focus on their potential clinical applications. Copyright © 2014 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                25 April 2017
                May 2017
                : 18
                : 5
                : 904
                Affiliations
                [1 ]Group of Reproductive Biology, Institute of Biotechnology CAS, v.v.i., BIOCEV, Prumyslova 595, 25250 Vestec, Czech Republic; pavla.dostalova@ 123456ibt.cas.cz (P.D.); eva.zatecka@ 123456ibt.cas.cz (E.Z.)
                [2 ]Department of Zoology, Faculty of Science, Charles University, Vinicna 7, 12844 Prague 2, Czech Republic
                Author notes
                [* ]Correspondence: katerina.hortova@ 123456ibt.cas.cz ; Tel.: +420-32-587-3799
                Article
                ijms-18-00904
                10.3390/ijms18050904
                5454817
                28441342
                ef8f546f-461e-485f-a508-1ef8eee6c892
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 January 2017
                : 20 April 2017
                Categories
                Review

                Molecular biology
                oestrogens,oestrogen receptors,testes,sperm,signalling,oestrogen-like compounds,humans,mice,rats,pigs

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