Human chorionic gonadotropin improves endometrial receptivity by increasing the expression of homeobox A10

Abstract Homeobox A10 (HOXA10) is a characterized marker of endometrial receptivity. The mechanism by which hCG intrauterine infusion promotes embryo implantation is still unclear. This study seeks to investigate whether hCG improves endometrial receptivity by increasing expression of HOXA10. HOXA10 expression with human chorionic gonadotropin stimulation was analyzed in vitro and in vivo. Our results demonstrate that HOXA10 was decreased in the endometria of recurrent implantation failure patients compared to that in the healthy control fertile group, also we observed that hCG intrauterine infusion increased endometrial HOXA10 expression. HOXA10, blastocyst-like spheroid expansion area was increased, whereas DNA (cytosine-5-)-methyltransferase 1 was decreased when human endometrial stromal cells (hESCs) were treated with 0.2 IU/ml of hCG for 48 h. HOXA10 promoter methylation was also reduced after hCG treatment. Collagen XV (ColXV) can repress the expression of DNA (cytosine-5-)-methyltransferase 1, and hCG treatment increased the expression of ColXV. However, when the hESCs were treated with LH/hCG receptor small interfering RNA to knock down LH/hCG receptor, hCG treatment failed to repress DNA (cytosine-5-)-methyltransferase 1 expression or to increase ColXV expression. Our findings suggest that hCG may promote embryo implantation by increasing the expression of HOXA10.

Download Full-text

Human chorionic gonadotropin block Smad2/3-mediated signalling of transforming growth factor β in human endometrial stromal cells, regulating the secretion of extracellular matrix remodelling elements and facilitating HTR8-SVneo invasion in vitro

Placenta ◽

10.1016/j.placenta.2017.01.133 ◽

2017 ◽

Vol 51 ◽

pp. 111-112

Author(s):

K. Zavaleta ◽

R. Gonzalez-Ramos ◽

M.C. Johnson ◽

A. Tapia-Pizarro

Keyword(s):

Extracellular Matrix ◽

Growth Factor ◽

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Stromal Cells ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Endometrial Stromal Cells ◽

Extracellular Matrix Remodelling

Download Full-text

P–322 Addressing progesterone and cAMP signalling pathways for decidualization induction of endometrial stromal cells of patients with endometriosis

Human Reproduction ◽

10.1093/humrep/deab130.321 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

J Moyer ◽

D Dunj. Baston-Buest ◽

G Wennemuth ◽

A Bielfeld ◽

R Grümmer

Keyword(s):

Stromal Cells ◽

Day Treatment ◽

Embryo Implantation ◽

Flow Cytometric Analysis ◽

Prolactin Secretion ◽

In Vivo Model ◽

Endometrial Stromal Cells ◽

Simultaneous Application

Abstract Study question Which compounds/compound combinations are most effective in decidualization induction of endometrial stromal cells (ESCs) of patients with and without endometriosis? Summary answer Combination of compounds addressing different steps in the signalling cascade of decidualization induce decidualization more effectively than application of the individual compounds alone. What is known already Decidualization is the monthly recurring differentiation process of the ESCs in preparation for embryo implantation in human. Undifferentiated ESCs reveal an increased potential to proliferate and invade after retrograde menstruation. This may lead to the formation of ectopic lesions and the manifestation of the chronic gynaecological disease of endometriosis due to an impairment of the decidualization process. Study design, size, duration Compounds and compound combinations addressing the progesterone receptor- or the cAMP-mediated pathway were evaluated with regard to their own and their synergistic potential to induce decidualization of ESCs from women with (n = 10) and without (n = 10) endometriosis during a 6-day treatment. Participants/materials, setting, methods Human primary ESCs were isolated via enzymatic-mechanic digestion from eutopic endometrium from women with and without endometriosis and treated for 6 days in vitro with different progestins (progesterone, medoxyprogesterone acetate (MPA)), 8-Br-cAMP, forskolin, or phosphodiesterase (PDE)-inhibitor (Rolipram) alone or in combination. The degree of decidualization induction was quantified by morphological, biochemical (prolactin) and molecular (HAND2, FOXO1) parameters by means of ELISA, flow cytometric analysis, Realtime PCR and Western blot analysis. Main results and the role of chance After 6 days of treatment, decidualization was induced by forskolin as well as by 8-Br-cAMP whereas progestins or PDE alone hardly induced prolactin secretion by ESCs as a marker of decidualization. A change of morphology from undifferentiated fibroblast-like cells to rounded cells could be observed in parallel with the secretion of prolactin. Forskolin and 8-Br-cAMP-induced decidualization was significantly enhanced by MPA but not by progesterone. These effects were similar in ESCs from women with and without endometriosis. Moreover, forskolin-induced decidualization was significantly enhanced by simultaneous application of PDE. Interestingly, this effect was higher in cells of patients with endometriosis. An induction of decidualization in ESCs was associated with a parallel increase of the process-associated transcription factors HAND2 and FOXO1. This rise of transcription was markedly increased in combination with MPA but not with progesterone. Limitations, reasons for caution Endometrial tissue was obtained from women undergoing infertility treatment and thus may differ from the endometrium of fertile women. Results obtained from primary cells in vitro may not cover the in vivo situation in all respects. Wider implications of the findings: The results of this study provide baseline data for the development of a possible therapeutical approach to induce decidualization as a treatment option for endometriosis. Further research is required to determine the effectiveness of the in vitro tested compound combinations in an in vivo model. Trial registration number Not applicable

Download Full-text

P-322 Addressing progesterone and cAMP signalling pathways for decidualization induction of endometrial stromal cells of patients with endometriosis

Human Reproduction ◽

10.1093/humrep/deab127.077 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

J Moyer ◽

D Dunja Baston-Buest ◽

G Wennemuth ◽

A Bielfeld ◽

R Grümmer

Keyword(s):

Stromal Cells ◽

Day Treatment ◽

Embryo Implantation ◽

Flow Cytometric Analysis ◽

Prolactin Secretion ◽

In Vivo Model ◽

Endometrial Stromal Cells ◽

Simultaneous Application

Abstract Study question Which compounds/compound combinations are most effective in decidualization induction of endometrial stromal cells (ESCs) of patients with and without endometriosis? Summary answer Combination of compounds addressing different steps in the signalling cascade of decidualization induce decidualization more effectively than application of the individual compounds alone. What is known already Decidualization is the monthly recurring differentiation process of the ESCs in preparation for embryo implantation in human. Undifferentiated ESCs reveal an increased potential to proliferate and invade after retrograde menstruation. This may lead to the formation of ectopic lesions and the manifestation of the chronic gynaecological disease of endometriosis due to an impairment of the decidualization process. Study design, size, duration Compounds and compound combinations addressing the progesterone receptor- or the cAMP-mediated pathway were evaluated with regard to their own and their synergistic potential to induce decidualization of ESCs from women with (n = 10) and without (n = 10) endometriosis during a 6-day treatment. Participants/materials, setting, methods Human primary ESCs were isolated via enzymatic-mechanic digestion from eutopic endometrium from women with and without endometriosis and treated for 6 days in vitro with different progestins (progesterone, medoxyprogesterone acetate (MPA)), 8-Br-cAMP, forskolin, or phosphodiesterase (PDE)-inhibitor (Rolipram) alone or in combination. The degree of decidualization induction was quantified by morphological, biochemical (prolactin) and molecular (HAND2, FOXO1) parameters by means of ELISA, flow cytometric analysis, Realtime PCR and Western blot analysis. Main results and the role of chance After 6 days of treatment, decidualization was induced by forskolin as well as by 8-Br-cAMP whereas progestins or PDE alone hardly induced prolactin secretion by ESCs as a marker of decidualization. A change of morphology from undifferentiated fibroblast-like cells to rounded cells could be observed in parallel with the secretion of prolactin. Forskolin and 8-Br-cAMP-induced decidualization was significantly enhanced by MPA but not by progesterone. These effects were similar in ESCs from women with and without endometriosis. Moreover, forskolin-induced decidualization was significantly enhanced by simultaneous application of PDE. Interestingly, this effect was higher in cells of patients with endometriosis. An induction of decidualization in ESCs was associated with a parallel increase of the process-associated transcription factors HAND2 and FOXO1. This rise of transcription was markedly increased in combination with MPA but not with progesterone. Limitations, reasons for caution Endometrial tissue was obtained from women undergoing infertility treatment and thus may differ from the endometrium of fertile women. Results obtained from primary cells in vitro may not cover the in vivo situation in all respects. Wider implications of the findings The results of this study provide baseline data for the development of a possible therapeutical approach to induce decidualization as a treatment option for endometriosis. Further research is required to determine the effectiveness of the in vitro tested compound combinations in an in vivo model. Trial registration number not applicable

Download Full-text

Inhibition of tumor growth in vitro and in vivo by a monoclonal antibody against human chorionic gonadotropin β

Immunology Letters ◽

10.1016/j.imlet.2007.09.005 ◽

2007 ◽

Vol 114 (2) ◽

pp. 94-102 ◽

Cited By ~ 6

Author(s):

Ning Yu ◽

Wei Xu ◽

Zhenggang Jiang ◽

Qinghua Cao ◽

Yiwei Chu ◽

...

Keyword(s):

Monoclonal Antibody ◽

Tumor Growth ◽

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Inhibition Of Tumor Growth

Download Full-text

Effects of the antiandrogen hydroxyflutamide on progesterone secretion by preovulatory rat follicles in vivo and in vitro

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y91-189 ◽

1991 ◽

Vol 69 (9) ◽

pp. 1288-1293 ◽

Cited By ~ 1

Author(s):

Yallampalli Chandrasekhar ◽

David T. Armstrong

Keyword(s):

Luteinizing Hormone ◽

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Serum Progesterone ◽

Antagonistic Action ◽

Lh Surge ◽

Progesterone Secretion ◽

Preovulatory Follicles

Serum and ovarian progesterone levels and in vitro production of progesterone by preovulatory follicles were measured on proestrus in pregnant mare's serum gonadotropin (PMSG) primed immature rats in which the luteinizing hormone (LH) surge and ovulation were blocked by administration of the antiandrogen hydroxyflutamide. Serum progesterone levels observed at 12:00 on proestrus were significantly elevated, twofold above those observed in vehicle-treated controls, by in vivo administration of 5 mg hydroxyflutamide 4 h earlier. In control rats, proestrous progesterone did not increase until 16:00, in parallel with rising LH levels of the LH surge. No LH surge occurred in the hydroxyflutamide-treated rats, ovulation was blocked, and serum progesterone declined throughout the afternoon of proestrus, from the elevated levels present at 12:00. Administration of human chorionic gonadotropin (hCG) at 11:00 advanced the elevation of serum progesterone by 2 h in vehicle-treated controls and prevented the decline in progesterone levels in hydroxyfiutamide-treated rats. The patterns of change in ovarian tissue concentrations with time and treatment were essentially similar to those observed for serum progesterone. In in vitro experiments, progesterone secretion during 24 h culture of preovulatory follicles obtained on PMSG-induced proestrus was significantly increased, sixfold, by addition to the culture media of 370 μM but not of 37 μM hydroxyflutamide. Testosterone (50 nM) and hCG (20 mIU/mL) caused 26- and 14-fold increases, respectively, in progesterone secretion by cultured follicles. Hydroxyflutamide significantly reduced the stimulatory effect of testosterone but not of hCG on progesterone secretion in vitro. These results suggest that the antiandrogen hydroxyflutamide stimulates progesterone secretion, both in vivo and in vitro, through an initial androgen-agonistic action, before its antagonistic action is expressed. Its androgen-antagonistic action is responsible for its ability to inhibit testosterone-induced progesterone secretion in vitro. Its failure to reduce hCG-stimulated progesterone secretion in vivo and in vitro indicates that the latter stimulation is exerted independently of, and not as a consequence of, androgen action. The decrease in serum progesterone levels on the afternoon of proestrus therefore appears to be a consequence rather than a cause of the absence of an LH surge in the hydroxyflutamide-treated rats. It is concluded that the inhibitory effect of hydroxyflutamide on the preovulatory LH surge and ovulation is due not to inhibition of progesterone secretion at the ovarian level but most likely to neuroendocrine site(s) of action of the inhibitor.Key words: antiandrogen, hydroxyflutamide, progesterone, luteinizing hormone, ovulation, human chorionic gonadotropin.

Download Full-text

Reduction of Testicular Human Chorionic Gonadotropin Receptors by Human Chorionic Gonadotropin in vivo and in vitro

Hormone Research ◽

10.1159/000180994 ◽

1988 ◽

Vol 29 (4) ◽

pp. 156-161 ◽

Cited By ~ 4

Author(s):

Mikio Namiki ◽

Masaya Kitamura ◽

Norio Nonomura ◽

Masahiro Nakamura ◽

Akihiko Okuyama ◽

...

Keyword(s):

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Gonadotropin Receptors

Download Full-text

Asialoagalacto-human chorionic gonadotropin, a carbohydrate-modified variant of human chorionic gonadotropin, antagonizes the stimulatory actions of bovine thyroid-stimulating hormone on thyroid function and HLA-DR expression in human thyroid in vitro and in vivo.

Journal of Clinical Investigation ◽

10.1172/jci115519 ◽

1991 ◽

Vol 88 (6) ◽

pp. 1947-1954 ◽

Cited By ~ 11

Author(s):

R Hoermann ◽

P M Schumm-Draeger ◽

K Rehbach ◽

K Mann

Keyword(s):

Thyroid Function ◽

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Thyroid Stimulating Hormone ◽

Human Thyroid ◽

Hla Dr ◽

Bovine Thyroid ◽

Stimulating Hormone

Download Full-text

Free α-Subunit, Free β-Subunit of Human Chorionic Gonadotropin (hCG), and Intact hCG in Sera of Healthy Individuals and Testicular Cancer Patients

Clinical Chemistry ◽

10.1093/clinchem/38.3.370 ◽

1992 ◽

Vol 38 (3) ◽

pp. 370-376 ◽

Cited By ~ 31

Author(s):

S Madersbacher ◽

R Klieber ◽

K Mann ◽

C Marth ◽

M Tabarelli ◽

...

Keyword(s):

Testicular Cancer ◽

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Beta Subunit ◽

Alpha Subunit ◽

Serum Concentrations ◽

Healthy Individuals ◽

Pathological Conditions

Abstract To determine the serum concentrations of human chorionic gonadotropin (hCG), its free beta-subunit (hCG beta), and the free alpha-subunit (free alpha) common to all human glycoprotein hormones under physiological and pathological conditions, we developed monoclonal antibody-based immunoenzymometric assays. Free alpha-subunit was detected in the sera of all healthy individuals of both sexes; hCG was measurable in sera of 54% of the men, and 46% were positive for free hCG beta; in nonpregnant women, 69.5% were positive for hCG, 68.4% for the free beta-subunit. Pathological conditions, i.e., hCG-producing tumors, were studied in vitro and in vivo. In vitro, the concentrations of hCG, free hCG beta, and free alpha in tissue-culture supernates of a choriocarcinoma cell-line ("JAR") showed a parallel pattern during time-course analysis. In vivo, in long-term follow-up studies of 13 patients with testicular cancer, serum concentrations of the three analytes paralleled each other, whether the disease was in remission or not. Because of a selective increase of free hCG beta and free alpha in 27% of seminomatous tumor patients and in 13% of the nonseminomatous patients, the percentage of tumor-marker-positive sera was increased from 15% to 42% and 57% to 70%, respectively, by the additional measurement of free hCG beta and free alpha. Thus hCG, free hCG beta, and free alpha are physiologically present in a high percentage of the sera from healthy men, and the determination of free hCG beta and free alpha, although not of prognostic value, improves the diagnostic possibilities in patients with testicular cancer.

Download Full-text