Localization and hormonal regulation of endometrial matrix metalloproteinase-26 in the rhesus macaque

C. C D Almeida-Francia, C. S. Keator, K. Mah, L. Holden, C. Hergert, Ov Slayden

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    Background: The current understanding of hormonal regulation of matrix metalloproteinase-26 (MMP-26) in the primate endometrium is incomplete. The goal of this work was to clarify estrogen and progesterone regulation of MMP-26 in the endometrium of ovariectomized, hormone-treated rhesus macaques. Methods Ovariectomized rhesus macaques (n 66) were treated with estradiol (E2), E2 plus progesterone, E2 followed by progesterone alone or no hormone. Endometrium was collected from the hormone-treated animals during the early, mid-and late proliferative and secretory phases of the artificial menstrual cycle. MMP-26 expression was quantified by real-time PCR, and MMP-26 transcript and protein were localized by in situ hybridization and immunohistochemistry and correlated with estrogen receptor 1 and progesterone receptor (PGR). Results MMP-26 was localized to glandular epithelium and was undetectable in the endometrial stroma and vasculature. MMP-26 transcript levels were minimal in the hormone-deprived macaques and treatment with E2 alone did not affect MMP-26 levels. Treatment with progesterone both in the presence and absence of E2 stimulated MMP-26 expression in the early and mid-secretory phases (P <0.001). MMP-26 expression preceded decidualization of endometrial stroma. MMP-26 levels then declined to baseline in the late secretory phase (P <0.01) despite continued E2 plus progesterone treatment. Loss of detectable MMP-26 expression in the late secretory phase was correlated with late secretory phase loss of glandular epithelial PGR. Conclusions Endometrial MMP-26 expression is dependent on the presence of progesterone in the early secretory phase and then gradually becomes refractory to progesterone stimulation in the late secretory phase. In the macaque, MMP-26 is a marker of the pre-decidual, secretory endometrium. During the second half of the late secretory phase, and during decidualization, MMP-26 loses its response to progesterone concurrent with the loss of epithelial PGR. The decline in MMP-26 levels between the mid-and late secretory phases may play a role in the receptive window for embryo implantation.

    Original languageEnglish (US)
    Pages (from-to)1723-1734
    Number of pages12
    JournalHuman Reproduction
    Volume27
    Issue number6
    DOIs
    StatePublished - Jun 2012

    Fingerprint

    Macaca mulatta
    Matrix Metalloproteinases
    Progesterone
    Endometrium
    Progesterone Receptors
    Hormones
    Macaca
    Estrogen Receptor alpha
    Luteal Phase
    Primates
    In Situ Hybridization
    Real-Time Polymerase Chain Reaction
    Estradiol
    Estrogens
    Therapeutics
    Epithelium

    Keywords

    • Endometrium
    • Estradiol
    • Matrix metalloproteinase-26
    • Progesterone
    • Rhesus macaque

    ASJC Scopus subject areas

    • Rehabilitation
    • Obstetrics and Gynecology
    • Reproductive Medicine

    Cite this

    Localization and hormonal regulation of endometrial matrix metalloproteinase-26 in the rhesus macaque. / Almeida-Francia, C. C D; Keator, C. S.; Mah, K.; Holden, L.; Hergert, C.; Slayden, Ov.

    In: Human Reproduction, Vol. 27, No. 6, 06.2012, p. 1723-1734.

    Research output: Contribution to journalArticle

    Almeida-Francia, C. C D ; Keator, C. S. ; Mah, K. ; Holden, L. ; Hergert, C. ; Slayden, Ov. / Localization and hormonal regulation of endometrial matrix metalloproteinase-26 in the rhesus macaque. In: Human Reproduction. 2012 ; Vol. 27, No. 6. pp. 1723-1734.
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    abstract = "Background: The current understanding of hormonal regulation of matrix metalloproteinase-26 (MMP-26) in the primate endometrium is incomplete. The goal of this work was to clarify estrogen and progesterone regulation of MMP-26 in the endometrium of ovariectomized, hormone-treated rhesus macaques. Methods Ovariectomized rhesus macaques (n 66) were treated with estradiol (E2), E2 plus progesterone, E2 followed by progesterone alone or no hormone. Endometrium was collected from the hormone-treated animals during the early, mid-and late proliferative and secretory phases of the artificial menstrual cycle. MMP-26 expression was quantified by real-time PCR, and MMP-26 transcript and protein were localized by in situ hybridization and immunohistochemistry and correlated with estrogen receptor 1 and progesterone receptor (PGR). Results MMP-26 was localized to glandular epithelium and was undetectable in the endometrial stroma and vasculature. MMP-26 transcript levels were minimal in the hormone-deprived macaques and treatment with E2 alone did not affect MMP-26 levels. Treatment with progesterone both in the presence and absence of E2 stimulated MMP-26 expression in the early and mid-secretory phases (P <0.001). MMP-26 expression preceded decidualization of endometrial stroma. MMP-26 levels then declined to baseline in the late secretory phase (P <0.01) despite continued E2 plus progesterone treatment. Loss of detectable MMP-26 expression in the late secretory phase was correlated with late secretory phase loss of glandular epithelial PGR. Conclusions Endometrial MMP-26 expression is dependent on the presence of progesterone in the early secretory phase and then gradually becomes refractory to progesterone stimulation in the late secretory phase. In the macaque, MMP-26 is a marker of the pre-decidual, secretory endometrium. During the second half of the late secretory phase, and during decidualization, MMP-26 loses its response to progesterone concurrent with the loss of epithelial PGR. The decline in MMP-26 levels between the mid-and late secretory phases may play a role in the receptive window for embryo implantation.",
    keywords = "Endometrium, Estradiol, Matrix metalloproteinase-26, Progesterone, Rhesus macaque",
    author = "Almeida-Francia, {C. C D} and Keator, {C. S.} and K. Mah and L. Holden and C. Hergert and Ov Slayden",
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    T1 - Localization and hormonal regulation of endometrial matrix metalloproteinase-26 in the rhesus macaque

    AU - Almeida-Francia, C. C D

    AU - Keator, C. S.

    AU - Mah, K.

    AU - Holden, L.

    AU - Hergert, C.

    AU - Slayden, Ov

    PY - 2012/6

    Y1 - 2012/6

    N2 - Background: The current understanding of hormonal regulation of matrix metalloproteinase-26 (MMP-26) in the primate endometrium is incomplete. The goal of this work was to clarify estrogen and progesterone regulation of MMP-26 in the endometrium of ovariectomized, hormone-treated rhesus macaques. Methods Ovariectomized rhesus macaques (n 66) were treated with estradiol (E2), E2 plus progesterone, E2 followed by progesterone alone or no hormone. Endometrium was collected from the hormone-treated animals during the early, mid-and late proliferative and secretory phases of the artificial menstrual cycle. MMP-26 expression was quantified by real-time PCR, and MMP-26 transcript and protein were localized by in situ hybridization and immunohistochemistry and correlated with estrogen receptor 1 and progesterone receptor (PGR). Results MMP-26 was localized to glandular epithelium and was undetectable in the endometrial stroma and vasculature. MMP-26 transcript levels were minimal in the hormone-deprived macaques and treatment with E2 alone did not affect MMP-26 levels. Treatment with progesterone both in the presence and absence of E2 stimulated MMP-26 expression in the early and mid-secretory phases (P <0.001). MMP-26 expression preceded decidualization of endometrial stroma. MMP-26 levels then declined to baseline in the late secretory phase (P <0.01) despite continued E2 plus progesterone treatment. Loss of detectable MMP-26 expression in the late secretory phase was correlated with late secretory phase loss of glandular epithelial PGR. Conclusions Endometrial MMP-26 expression is dependent on the presence of progesterone in the early secretory phase and then gradually becomes refractory to progesterone stimulation in the late secretory phase. In the macaque, MMP-26 is a marker of the pre-decidual, secretory endometrium. During the second half of the late secretory phase, and during decidualization, MMP-26 loses its response to progesterone concurrent with the loss of epithelial PGR. The decline in MMP-26 levels between the mid-and late secretory phases may play a role in the receptive window for embryo implantation.

    AB - Background: The current understanding of hormonal regulation of matrix metalloproteinase-26 (MMP-26) in the primate endometrium is incomplete. The goal of this work was to clarify estrogen and progesterone regulation of MMP-26 in the endometrium of ovariectomized, hormone-treated rhesus macaques. Methods Ovariectomized rhesus macaques (n 66) were treated with estradiol (E2), E2 plus progesterone, E2 followed by progesterone alone or no hormone. Endometrium was collected from the hormone-treated animals during the early, mid-and late proliferative and secretory phases of the artificial menstrual cycle. MMP-26 expression was quantified by real-time PCR, and MMP-26 transcript and protein were localized by in situ hybridization and immunohistochemistry and correlated with estrogen receptor 1 and progesterone receptor (PGR). Results MMP-26 was localized to glandular epithelium and was undetectable in the endometrial stroma and vasculature. MMP-26 transcript levels were minimal in the hormone-deprived macaques and treatment with E2 alone did not affect MMP-26 levels. Treatment with progesterone both in the presence and absence of E2 stimulated MMP-26 expression in the early and mid-secretory phases (P <0.001). MMP-26 expression preceded decidualization of endometrial stroma. MMP-26 levels then declined to baseline in the late secretory phase (P <0.01) despite continued E2 plus progesterone treatment. Loss of detectable MMP-26 expression in the late secretory phase was correlated with late secretory phase loss of glandular epithelial PGR. Conclusions Endometrial MMP-26 expression is dependent on the presence of progesterone in the early secretory phase and then gradually becomes refractory to progesterone stimulation in the late secretory phase. In the macaque, MMP-26 is a marker of the pre-decidual, secretory endometrium. During the second half of the late secretory phase, and during decidualization, MMP-26 loses its response to progesterone concurrent with the loss of epithelial PGR. The decline in MMP-26 levels between the mid-and late secretory phases may play a role in the receptive window for embryo implantation.

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    KW - Estradiol

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    KW - Progesterone

    KW - Rhesus macaque

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