Expression of the oestrogen receptor GPER by testicular peritubular cells is linked to sexual maturation and male fertility

F. Sandner, H. Welter, J. U. Schwarzer, F. M. Köhn, Henryk Urbanski, A. Mayerhofer

    Research output: Contribution to journalArticle

    14 Citations (Scopus)

    Abstract

    Besides the two nuclear oestrogen receptors (ESR1/ESR2), the G protein-coupled oestrogen receptor (GPER) was described in the human testis but little is known about testicular GPER during development or male infertility. We performed an immunohistochemical analysis using human and rhesus monkey testicular samples. The results obtained in adult primate testes showed GPER in interstitial and vascular cells as well as in smooth muscle-like peritubular cells, which build the wall of seminiferous tubules. Expression of GPER was also found in cultured human testicular peritubular cells (HPTCs) by Western blotting and RT-PCR/sequencing. Furthermore, as seen in time-lapse videos of cultured cells, addition of a specific GPER agonist (G1) significantly reduced the numbers of HTPCs within 24 h. A GPER antagonist (G15) prevented this action, implying a role for GPER related to the control of cell proliferation or cell death of peritubular cells. Peritubular cell functions and their phenotype change, for example, during post-natal development and in the cases of male infertility. The study of non-human primate samples revealed that GPER in peritubular cells was detectable only from the time of puberty onwards, while in samples from infantile and prepubertal monkeys only interstitial cells showed immunopositive staining. In testicular biopsies of men with mixed atrophy, a reduction or loss of immunoreactive GPER was found in peritubular cells surrounding those tubules, in which spermatogenesis was impaired. In other cases of impaired spermatogenesis, namely when the tubular wall was fibrotically remodelled, a complete loss of GPER was seen. Thus, the observed inverse relation between the state of fertility and GPER expression by peritubular cells implies that the regulation of primate testicular peritubular cells by oestrogens is mediated by GPER in both, health and disease.

    Original languageEnglish (US)
    Pages (from-to)695-701
    Number of pages7
    JournalAndrology
    Volume2
    Issue number5
    DOIs
    StatePublished - 2014

    Fingerprint

    Sexual Maturation
    G-Protein-Coupled Receptors
    Estrogen Receptors
    Fertility
    Primates
    Male Infertility
    Spermatogenesis
    estrophilin
    Testis
    Estrogens
    Seminiferous Tubules
    Puberty
    Macaca mulatta
    Atrophy
    Haplorhini
    Smooth Muscle
    Blood Vessels
    Cultured Cells
    Cell Death

    Keywords

    • Cell culture
    • Development
    • Infertility
    • Seminiferous tubules
    • Sex hormone receptor

    ASJC Scopus subject areas

    • Endocrinology
    • Endocrinology, Diabetes and Metabolism
    • Reproductive Medicine
    • Urology

    Cite this

    Expression of the oestrogen receptor GPER by testicular peritubular cells is linked to sexual maturation and male fertility. / Sandner, F.; Welter, H.; Schwarzer, J. U.; Köhn, F. M.; Urbanski, Henryk; Mayerhofer, A.

    In: Andrology, Vol. 2, No. 5, 2014, p. 695-701.

    Research output: Contribution to journalArticle

    Sandner, F. ; Welter, H. ; Schwarzer, J. U. ; Köhn, F. M. ; Urbanski, Henryk ; Mayerhofer, A. / Expression of the oestrogen receptor GPER by testicular peritubular cells is linked to sexual maturation and male fertility. In: Andrology. 2014 ; Vol. 2, No. 5. pp. 695-701.
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    abstract = "Besides the two nuclear oestrogen receptors (ESR1/ESR2), the G protein-coupled oestrogen receptor (GPER) was described in the human testis but little is known about testicular GPER during development or male infertility. We performed an immunohistochemical analysis using human and rhesus monkey testicular samples. The results obtained in adult primate testes showed GPER in interstitial and vascular cells as well as in smooth muscle-like peritubular cells, which build the wall of seminiferous tubules. Expression of GPER was also found in cultured human testicular peritubular cells (HPTCs) by Western blotting and RT-PCR/sequencing. Furthermore, as seen in time-lapse videos of cultured cells, addition of a specific GPER agonist (G1) significantly reduced the numbers of HTPCs within 24 h. A GPER antagonist (G15) prevented this action, implying a role for GPER related to the control of cell proliferation or cell death of peritubular cells. Peritubular cell functions and their phenotype change, for example, during post-natal development and in the cases of male infertility. The study of non-human primate samples revealed that GPER in peritubular cells was detectable only from the time of puberty onwards, while in samples from infantile and prepubertal monkeys only interstitial cells showed immunopositive staining. In testicular biopsies of men with mixed atrophy, a reduction or loss of immunoreactive GPER was found in peritubular cells surrounding those tubules, in which spermatogenesis was impaired. In other cases of impaired spermatogenesis, namely when the tubular wall was fibrotically remodelled, a complete loss of GPER was seen. Thus, the observed inverse relation between the state of fertility and GPER expression by peritubular cells implies that the regulation of primate testicular peritubular cells by oestrogens is mediated by GPER in both, health and disease.",
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    AU - Urbanski, Henryk

    AU - Mayerhofer, A.

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