Uterus and endometrium: Changes in nuclear morphology in the human endometrial glandular epithelium in women with unexplained infertility

Dockery, Peter; Pritchard, K.; Warren, M.A.; Li, Tin‐Chiu; Cooke, I. D.

doi:10.1093/oxfordjournals.humrep.a019085

Cited by 20 publications

(10 citation statements)

References 23 publications

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“…Therefore, alterations in human endometrial gland formation and function may lead to infertility and early pregnancy loss. Decreased expression of cell-surface and secretory proteins within the uterine environment are correlated with abnormal uterine gland morphology that adversely affect uterine receptivity during the periimplantation and early placentation stages of gestation [44,46,47]. Perhaps these documented human reproductive defects can be related to defects in UGKO ewes wherein the absence of epithelial-specific gene expression [31] and histotroph production results in failure of conceptus development beyond the preimplantation period.…”

Section: Discussionmentioning

confidence: 99%

Endometrial Glands Are Required for Preimplantation Conceptus Elongation and Survival1

Gray

Taylor

Ramsey

et al. 2001

Biology of Reproduction

316

212

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Endometrial glands secrete molecules hypothesized to support conceptus growth and development. In sheep, endometrial gland morphogenesis occurs postnatally and can be epigenetically ablated by neonatal progestin exposure. The resulting stable adult uterine gland knockout (UGKO) phenotype was used here to test the hypothesis that endometrial glands are required for successful pregnancy. Mature UGKO ewes were bred repeatedly to fertile rams, but no pregnancies were detected by ultrasound on Day 25. Day 7 blastocysts from normal superovulated ewes were then transferred synchronously into Day 7 control or UGKO ewes. Ultrasonography on Days 25-65 postmating indicated that pregnancy was established in control, but not in UGKO ewes. To examine early uterine-embryo interactions, four control and eight UGKO ewes were bred to fertile rams. On Day 14, their uteri were flushed. The uterus of each control ewe contained two filamentous conceptuses of normal length. Uteri from four UGKO ewes contained no conceptus. Uteri of three UGKO ewes contained a single severely growth-retarded tubular conceptus, whereas the remaining ewe contained a single filamentous conceptus. Histological analyses of these uteri revealed that endometrial gland density was directly related to conceptus survival and developmental state. Day 14 UGKO uteri that were devoid of endometrial glands did not support normal conceptus development and contained either no conceptuses or growth-retarded tubular conceptuses. The Day 14 UGKO uterus with moderate gland development contained a filamentous conceptus. Collectively, these results demonstrate that endometrial glands and, by inference, their secretions are required for periimplantation conceptus survival and development.

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Section: Discussionmentioning

confidence: 99%

Endometrial Glands Are Required for Preimplantation Conceptus Elongation and Survival1

Gray

Taylor

Ramsey

et al. 2001

Biology of Reproduction

316

212

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“…Oral contraceptives and intrauterine devices interfere with the timing and/or overall appearance of the NCS (Wynn, 1967;Feria-Velasco et al, 1972;Azadian-Boulanger et al, 1976;van Santen et al, 1988;Dockery et al, 1997). Several cases of unexplained primary infertility have been characterized by the absence or delayed development of NCSs as the only ultrastructural alteration in endometrial epithelial cells (Kohorn et al, 1972;Gore and Gordon, 1974;Dockery et al, 1996). This and other correlative evidence suggests a role for the NCS in the preparation of the uterine surface for embryo implantation and points to the NCS as a long sought after marker for human receptivity.…”

Section: Introductionmentioning

confidence: 99%

The Nucleolar Channel System of Human Endometrium Is Related to Endoplasmic Reticulum and R-Rings

Kittur¹,

Zapantis

Aubuchon

et al. 2007

MBoC

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The nucleolar channel system (NCS) is a well-established ultrastructural hallmark of the postovulation endometrium. Its transient presence has been associated with human fertility. Nevertheless, the biogenesis, composition, and function of these intranuclear membrane cisternae are unknown. Membrane systems with a striking ultrastructural resemblance to the NCS, termed R-rings, are induced in nuclei of tissue culture cells by overexpression of the central repeat domain of the nucleolar protein Nopp140. Here we provide a first molecular characterization of the NCS and compare the biogenesis of these two enigmatic organelles. Like the R-rings, the NCS consists of endoplasmic reticulum harboring the marker glucose-6-phosphatase. R-ring formation initiates at the nuclear envelope, apparently by a calcium-mediated Nopp140-membrane interaction, as supported by the calcium-binding ability of Nopp140, the inhibition of R-ring formation by calcium chelators, and the concentration of Nopp140 and complexed calcium in R-rings. Although biogenesis of the NCS may initiate similarly, the reduced presence of complexed calcium and Nopp140 suggests the involvement of additional factors. INTRODUCTIONFor close to half a century, the nucleolar channel system (NCS) has been known as an ultrastructural hallmark of the postovulation human endometrium (Dubrauszky and Pohlmann, 1960;Clyman, 1963;Moricard and Moricard, 1964;Terzakis, 1965). It consists of several layers of tubular membrane cisternae in the nuclei of endometrial epithelial cells and is often associated with the nuclear envelope and nucleoli, hence the name (for a review see Spornitz, 1992). This organelle appears during a 3-to 4-d window in the midsecretory phase of the menstrual cycle when the endometrium is receptive to implantation of the fertilized egg (Clyman, 1963;Gordon, 1975). Oral contraceptives and intrauterine devices interfere with the timing and/or overall appearance of the NCS (Wynn, 1967;Feria-Velasco et al., 1972;Azadian-Boulanger et al., 1976;van Santen et al., 1988;Dockery et al., 1997). Several cases of unexplained primary infertility have been characterized by the absence or delayed development of NCSs as the only ultrastructural alteration in endometrial epithelial cells (Kohorn et al., 1972;Gore and Gordon, 1974;Dockery et al., 1996). This and other correlative evidence suggests a role for the NCS in the preparation of the uterine surface for embryo implantation and points to the NCS as a long sought after marker for human receptivity. Nevertheless, despite this tantalizing data and the detailed ultrastructural description of the NCS, it has resisted molecular characterization. Here we provide first insights as to the composition of this enigmatic organelle.On the basis of their remarkable ultrastructural resemblance to the NCS, we previously characterized membrane systems, R-rings, that are induced in nuclei of tissue culture cells by overexpression of the nucleolar protein Nopp140 (Isaac et al., 1998;Isaac et al., 2001). Nopp140 functions as a chaper...

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“…The NCS is specific to healthy, human EECs: It is not detected in endometrial stromal cell nuclei, human breast or gastrointestinal tract tissue, endometrial carcinoma specimens, or in baboon endometrium (6). Moreover, midluteal NCS presence is robust and independent of fertility status including unexplained infertility (7-9). …”

Section: Introductionmentioning

confidence: 99%

Quantification of nucleolar channel systems: uniform presence throughout the upper endometrial cavity

Szmyga

Rybak

Nejat

et al. 2013

Fertility and Sterility

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Objective To determine the prevalence of nucleolar channel systems (NCSs) by uterine region applying continuous quantification. Design Prospective clinical study. Setting Tertiary care academic medical center. Patients 42 naturally cycling women who underwent hysterectomy for benign indications. Intervention NCS presence was quantified by a novel method in six uterine regions, fundus, left cornu, right cornu, anterior body, posterior body, and lower uterine segment (LUS), using indirect immunofluorescence. Main Outcome Measures Percent of endometrial epithelial cells (EECs) with NCSs per uterine region. Results NCS quantification was observer-independent (intraclass correlation coefficient [ICC] = 0.96) and its intra-sample variability low (coefficient of variability [CV] = 0.06). 11/42 hysterectomy specimens were midluteal, 10 of which were analyzable with 9 containing over 5% EECs with NCSs in at least one region. The percent of EECs with NCSs varied significantly between the lower uterine segment (6.1%; IQR = 3.0-9.9) and the upper five regions (16.9%; IQR = 12.7-23.4) with fewer NCSs in the basal layer of the endometrium (17% +/−6%) versus the middle (46% +/−9%) and luminal layers (38% +/−9%) of all six regions). Conclusions NCS quantification during the midluteal phase demonstrates uniform presence throughout the endometrial cavity, excluding the LUS, with a preference for the functional, luminal layers. Our quantitative NCS evaluation provides a benchmark for future studies and further supports NCS presence as a potential marker for the window of implantation.

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Uterus and endometrium: Changes in nuclear morphology in the human endometrial glandular epithelium in women with unexplained infertility

Cited by 20 publications

References 23 publications

Endometrial Glands Are Required for Preimplantation Conceptus Elongation and Survival1

Endometrial Glands Are Required for Preimplantation Conceptus Elongation and Survival1

The Nucleolar Channel System of Human Endometrium Is Related to Endoplasmic Reticulum and R-Rings

Quantification of nucleolar channel systems: uniform presence throughout the upper endometrial cavity

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