Human choriogonadotrophin protein core and sugar branches heterogeneity: basic and clinical insights

Yamamoto, Márcia Marly Winck; Norman, Robert J.

doi:10.1093/humupd/dmn036

Cited by 54 publications

(40 citation statements)

References 267 publications

(259 reference statements)

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“…In early atherosclerotic lesions, macrophages do not take up native low-density lipoprotein but negatively charged oxidized low-density lipoprotein recognized by their scavenger receptors, subsequently forming foam cells [Steinberg and Witztum, 2010]. Intact hCG is more negatively charged in the early stage than in the late stage of gestation [Medeiros and Norman, 2009]. Human macrophages may recognize and incorporate more negatively charged hCG via transmembrane receptors, e.g.…”

Section: Discussionmentioning

confidence: 99%

Human Chorionic Gonadotropin Induces Human Macrophages to Form Intracytoplasmic Vacuoles Mimicking Hofbauer Cells in Human Chorionic Villi

Yamaguchi

Ohba²,

Tashiro³

et al. 2012

Cells Tissues Organs

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The most characteristic morphological feature of macrophages in the stroma of placental villi, known as Hofbauer cells, is their highly vacuolated appearance. They also show positive immunostaining for human chorionic gonadotropin (hCG) and express messenger ribonucleic acid of the luteinizing hormone/chorionic gonadotropin receptor with a deletion of exon 9 (LH/CG-R Δ9). Maternal hCG enters fetal plasma through the mesenchyme of the placental villi and promotes male sexual differentiation in early pregnancy; therefore, excess hCG may induce aberrant genital differentiation and hCG must be adjusted at the fetomaternal interface. We hypothesized that hCG is regulated by Hofbauer cells and that their peculiar vacuoles are involved in a cell-specific function. To assess the morphological modification and expression of LH/CG-R Δ9 in human macrophages after hCG exposure, the present study examined phorbol 12-myristate 13-acetate (PMA)-treated THP-1 cells, a human monocyte-macrophage cell line. hCG induced transient vacuole formation in PMA-treated THP-1 cells, morphologically mimicking Hofbauer cells. Immunocytochemistry showed that PMA-treated THP-1 cells incorporated hCG but not luteinizing hormone or follicle-stimulating hormone. Western blotting analyses demonstrated that PMA-treated THP-1 cells expressed an immunoreactive 60-kDa protein, designated as endogenous LH/CG-R Δ9. hCG induced a transient reduction in the LH/CG-R Δ9, which was synchronous with the appearance of cytoplasmic vacuoles. In conclusion, human macrophages regulating hCG via cytoplasmic LH/CG-R Δ9 mimic the morphological characteristics of Hofbauer cells. Their vacuoles may be associated with their cell-specific function to protect the fetus from exposure to excess maternal hCG during pregnancy.

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Section: Discussionmentioning

confidence: 99%

Human Chorionic Gonadotropin Induces Human Macrophages to Form Intracytoplasmic Vacuoles Mimicking Hofbauer Cells in Human Chorionic Villi

Yamaguchi

Ohba²,

Tashiro³

et al. 2012

Cells Tissues Organs

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“…Either high or diminished concentrations of intact hCG have been associated with maternal or embryo-placenta abnormalities. Its measurements becomes a useful method to detect higher risk of miscarriage, ectopic pregnancy, predict pre-eclampsia, intrauterine fetal growth restriction, fetal hydrops or identify trisomy [14]. Recently an electrochemiluminescence (ECL) method has been able to detect intact hCG secreted by embryos in spent culture media of day 1, day 3 and day 5 [15].…”

Section: Signals At the Same Timementioning

confidence: 99%

Signal Transduction of hCG Induces Decidualization and Uterine Receptivity

Bernardini¹,

Balmaceda

Gianaroli³

et al. 2017

JFB

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All independent experimental data on epithelial and glandular cells lines of human endometrium support the evidence for a rapid production of eicosanoids from the LH/hCG receptors when exposed to the hCG hormone. Prostaglandins rapidly act on the surrounding endometrial stromal cells throughout the adenylyl cyclase enzyme leading to very large amounts of cAMP and angiogenic factors (VEGF) production. The cAMP is the most important intracellular second messenger and along with progesterone accomplishes the full process of decidualization and acquisition of receptivity after estrogenic priming of the endometrium. The status of uterine receptivity lasts few days only and timing for successful embryo-signal transduction system activation by the endometrium is probably short. In absence of in vivo embryonic signals it is impossible to predict, on individual bases, how the intensity of all the complex interlinked molecular changes of decidualization might ever be in case of exposure to native hCG. In other terms, amount of prostaglandins and cAMP produced in response to variably glycosylated hCG are all, in vivo, not measurable variables and should be viewed as a "wave" of biochemical chain reactions. Embryonic hCG is secreted in form of multiple isomers having an unpredictable variable level of glycosylation and control of this variable remains elusive.During cycles of ovarian stimulation many drugs (FSH, LH, HCG) interact with different G-protein coupled receptors (GPCRs) making it possible to alter the prostaglandins-mediated decidualization process ready to be elicited only by hCG of pregnancy. Since the molecules (cAMP and progesterone) controlling endometrial stromal cells differentiation into decidual cells are critical for successful implantation and placenta formation, the evidence of fast eicosanoids production associated with endometrial LH/hCG receptors exposure to hCG and the potential by human endometrium to produce, in response, very large amounts of cAMP has biological and clinical relevance.

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“…Initial work conducted by our group using the resources of the Northern Sweden Maternity Cohort (NSMC), relating early pregnancy hCG to subsequent risk of maternal breast cancer, provide direct human evidence in support of these observations [5,6]. HCG is composed of two distinct noncovalently associated α- and β-subunits and has six major isoforms [7] with different biological properties [8,9]. The most widely used assays for hCG determination that are practical for use in epidemiological studies are total, intact and free β-hCG (free β-hCG).…”

Section: Introductionmentioning

confidence: 99%

Free β-human Chorionic Gonadotropin, Total Human Chorionic Gonadotropin and Maternal Risk of Breast Cancer

et al. 2014

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Background We investigated whether the free β-human chorionic gonadotropin (free β-hCG) would provide additional information to that provided by total hCG alone and thus be useful in future epidemiological studies relating hCG to maternal breast cancer risk. Materials & methods Cases (n = 159) and controls (n = 286) were a subset of our previous study within the Northern Sweden Maternity Cohort on total hCG during primiparous pregnancy and breast cancer risk. Results The associations between total hCG (hazard ratio: 0.79; 95% CI: 0.49–1.27), free β-hCG (hazard ratio: 0.85; 95% CI: 0.33–2.18) and maternal risk of breast cancer were very similar in all analyses and mutual adjustment for either one had minor effects on the risk estimates. Conclusion In the absence of a reliable assay on intact hCG, total hCG alone can be used in epidemiological studies investigating hCG and breast cancer risk, as free β-hCG does not appear to provide any additional information.

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Human choriogonadotrophin protein core and sugar branches heterogeneity: basic and clinical insights

Abstract: Measurement of hCG and/or its related molecules is useful in clinical practice, but greater awareness is needed worldwide regarding the use of new sensitive and specific assays tailored for different clinical applications.

Cited by 54 publications

References 267 publications

Human Chorionic Gonadotropin Induces Human Macrophages to Form Intracytoplasmic Vacuoles Mimicking Hofbauer Cells in Human Chorionic Villi

Human Chorionic Gonadotropin Induces Human Macrophages to Form Intracytoplasmic Vacuoles Mimicking Hofbauer Cells in Human Chorionic Villi

Signal Transduction of hCG Induces Decidualization and Uterine Receptivity

Free β-human Chorionic Gonadotropin, Total Human Chorionic Gonadotropin and Maternal Risk of Breast Cancer

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