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      Absorption and distribution of estradiol from male seminal emissions during mating

      research-article
      ,
      The Journal of Endocrinology
      Bioscientifica Ltd
      estrogen, female reproduction, uterus, reproduction, behaviour

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          Abstract

          Estradiol-17β (E 2) plays critical roles in female maturation, sexual receptivity, ovulation and fertility. In many mammals, contact with males can similarly affect these female parameters, whereas male excretions contain significant quantities of E 2. We administered radiolabeled estradiol ([ 3H]E 2) to male mice in doses representing a small fraction of their endogenous E 2. These males were paired with sexually receptive females, and radioactivity was traced into the females’ systems. In Experiment 1, males were given [ 3H]E 2 at 24 and 1 h before mating. Male-to-female [ 3H]E 2 transfer intensified with increasing numbers of intromissions and spiked in the uterus after insemination. In Experiment 2, sexually experienced young males received [ 3H]E 2 at 72 and 24 h before mating, and all mated to ejaculation. The copulatory plug deposited in the female reproductive tract contained substantial levels of radioactivity. The uteri, other tissues and blood serum of females displayed radioactivity indicative of E 2 transfer. In Experiment 3, radioactivity was observed 3 and 18 h after insemination in the females’ uteri and other tissues, including parts of the brain. In Experiment 4, we observed substantial levels of radioactivity in semen as well as the copulatory plugs retrieved from the females after mating. Transferred E 2 could directly affect abundant estrogen receptors in the female reproductive tract without potential metabolism by the liver. Sexually transferred E 2 may facilitate uterine preparation for blastocyst implantation. These data converge with several lines of evidence indicating that male-sourced E 2 can transfer to proximate females in bioactive form, contributing to various mammalian pheromonal effects.

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          Most cited references58

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          Molecular cues to implantation.

          Successful implantation is the result of reciprocal interactions between the implantation-competent blastocyst and receptive uterus. Although various cellular aspects and molecular pathways of this dialogue have been identified, a comprehensive understanding of the implantation process is still missing. The receptive state of the uterus, which lasts for a limited period, is defined as the time when the uterine environment is conducive to blastocyst acceptance and implantation. A better understanding of the molecular signals that regulate uterine receptivity and implantation competency of the blastocyst is of clinical relevance because unraveling the nature of these signals may lead to strategies to correct implantation failure and improve pregnancy rates. Gene expression studies and genetically engineered mouse models have provided valuable clues to the implantation process with respect to specific growth factors, cytokines, lipid mediators, adhesion molecules, and transcription factors. However, a staggering amount of information from microarray experiments is also being generated at a rapid pace. If properly annotated and explored, this information will expand our knowledge regarding yet-to-be-identified unique, complementary, and/or redundant molecular pathways in implantation. It is hoped that the forthcoming information will generate new ideas and concepts for a process that is essential for maintaining procreation and solving major reproductive health issues in women.
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            Estrogen is a critical determinant that specifies the duration of the window of uterine receptivity for implantation.

            Many underlying causes of human infertility have been overcome by using in vitro fertilization (IVF) and embryo transfer (ET) techniques. Nevertheless, implantation rates in IVF programs remain low despite the transfer of apparently healthy embryos. This suggests that there are problems with the differentiation of the uterus to the receptive state in response to the ovarian hormones estrogen and progesterone. The molecular basis of this receptive state when the uterine environment is conducive to blastocyst acceptance and implantation remains poorly understood. Normally, the "window" of uterine receptivity lasts for a limited time. Using ETs and the progesterone-treated delayed-implantation model in mice, we demonstrate here that levels of estrogen within a very narrow range determine the duration of the window of uterine receptivity. Although estrogen at different physiological concentrations can initiate implantation, we find that the window of uterine receptivity remains open for an extended period at lower estrogen levels but rapidly closes at higher levels. The uterine refractoriness that follows the receptive state at high estrogen levels is accompanied by aberrant uterine expression of implantation-related genes. These results suggest that careful regulation of estrogen levels is one of the important factors for improvement of female fertility in IVFET programs.
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              Tissue distribution and quantitative analysis of estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) messenger ribonucleic acid in the wild-type and ERalpha-knockout mouse.

              Until recently, only a single type of estrogen receptor (ER) was thought to exist and mediate the genomic effects of the hormone 17beta-estradiol in mammalian tissues. However, the cloning of a gene encoding a second type of ER, termed ERbeta, from the mouse, rat, and human has prompted a reevaluation of the estrogen signaling system. Based on in vitro studies, the ERbeta protein binds estradiol with an affinity similar to that of the classical ER (now referred to as ERalpha) and is able to mediate the effects of estradiol in transfected mammalian cell lines. Essential to further investigations of the possible physiological roles of ERbeta, and its possible interactions with ERalpha, are data on the tissue distribution of the two ER types. Herein, we have described the optimization and use of an RNase protection assay able to detect and distinguish messenger RNA (mRNA) transcripts from both the ERalpha and ERbeta genes in the mouse. Because this assay is directly quantitative, a comparison of the levels of expression within various tissues was possible. In addition, the effect of disruption of the ERalpha gene on the expression of the ERbeta gene was also investigated using the ERalpha-knockout (ERKO) mouse. Transcripts encoding ERalpha were detected in all the wild-type tissues assayed from both sexes. In the female reproductive tract, the highest expression of ERbeta mRNA was observed in the ovary and showed great variation among individual animals; detectable levels were observed in the uterus and oviduct, whereas mammary tissue was negative. In the male reproductive tract, significant expression of ERbeta was seen in the prostate and epididymis, whereas the testes were negative. In other tissues of both sexes, the hypothalamus and lung were clearly positive for both ERalpha and ERbeta mRNA. The ERKO mice demonstrated slightly reduced levels of ERbeta mRNA in the ovary, prostate, and epididymis. These data, in combination with the several described phenotypes in both sexes of the ERKO mouse, suggest that the biological functions of the ERbeta protein may be dependent on the presence of ERalpha in certain cell types and tissues. Further characterization of the physiological phenotypes in the ERKO mice may elucidate possible ERbeta specific actions.

                Author and article information

                Journal
                J Endocrinol
                J. Endocrinol
                JOE
                The Journal of Endocrinology
                Bioscientifica Ltd (Bristol )
                0022-0795
                1479-6805
                November 2016
                01 November 2016
                : 231
                : 3
                : 245-257
                Affiliations
                [1]Department of Psychology Neuroscience & Behaviour, McMaster University, Hamilton, Ontario, Canada
                Author notes
                Correspondence should be addressed to D deCatanzaro; Email: decatanz@ 123456mcmaster.ca
                Article
                JOE160247
                10.1530/JOE-16-0247
                5097127
                27758953
                5c07bd0a-ad6c-4402-840b-c8a3caadd05f
                © 2016 The authors

                This work is licensed under a Creative Commons Attribution 3.0 Unported License.

                History
                : 14 September 2016
                : 6 October 2016
                Categories
                Research

                Endocrinology & Diabetes
                estrogen,female reproduction,uterus,reproduction,behaviour
                Endocrinology & Diabetes
                estrogen, female reproduction, uterus, reproduction, behaviour

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