Endometrial human chorionic gonadotropin (hCG) expression is a marker for adequate secretory transformation of the endometrium
Successful embryo implantation into the endometrium depends on embryonic characteristics and proper endometrial development. Reproductive medicine often focuses on embryo quality, whereas reliable diagnostic tests for endometrial receptivity are still needed. We previously found that human chorionic gonadotropin (hCG), one of the earliest proteins secreted by the embryo, was also expressed by the luteal phase endometrium around the implantation window. Here, we tested our hypothesis of endometrial hCG as an implantation marker.
Endometrial biopsies and serum samples were taken from patients undergoing routine infertility diagnostics. Correlations of immunohistochemically detected endometrial hCG expression with adequate endometrial secretory transformation, the infiltration of CD45-positive leukocytes, clinical diagnostic parameters, and endometrial thickness were analyzed.
A highly significant correlation between the endometrial score, as a measurement for regular secretory transformation, and the intensity of hCG staining was found. The invasion of CD45-positive leukocytes increased with progressing endometrial secretory transformation and rising endometrial hCG expression. In addition, serum progesterone concentrations correlated with hCG expression by the endometrial glands.
Our results suggest endometrial hCG as a possible diagnostic parameter characterizing the endometrial secretory transformation and, thus, possibly also its implantation capability.
KeywordsHuman chorionic gonadotropin hCG Endometrium Implantation marker Reproductive medicine
Assisted reproductive technologies
Human chorionic gonadotropin beta subunit
Human chorionic gonadotropin
The authors thank Regina Scherling for expert technical assistance.
SS: data analysis and manuscript writing. AB: Protocol/project development, data collection and management, data analysis, and manuscript writing/editing. MG: data analysis. LCH: data analysis and manuscript editing. GP: contribution of endometrial specimens. GZ: protocol/project development, data analysis, and manuscript editing. HA: protocol/project development and manuscript editing.
S. Schug was supported by the German Research Foundation (DFG, Grant SO 1231/1-1) and a junior research grant awarded by the University of Leipzig Medical School.
Compliance with ethical standards
Conflict of interest
We declare that we have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.
Informed consent was obtained from all individual participants included in the study.
- 10.Lei ZM, Toth P, Rao CV, Pridham D (1993) Novel coexpression of human chorionic gonadotropin (hCG)/human luteinizing hormone receptors and their ligand hCG in human fallopian tubes. J Clin Endocrinol Metab 77:863–872Google Scholar
- 11.Alexander H, Biesold C, Weber W, Baier D (1997) [Immunohistochemical evidence of immuno-reactive hCG in the secretory endometrium in women]. Zentralbl Gynakol 119(Suppl 1):17–22Google Scholar
- 18.Policastro PF, Niels-McQueen S, Carle G, Boime I (1986) A map of the hCG beta-LH beta gene cluster. J Biol Chem 261:5907–5916Google Scholar
- 32.Paiva P, Hannan NJ, Hincks C, Meehan KL, Pruysers E, Dimitriadis E, Salamonsen LA (2011) Human chorionic gonadotrophin regulates FGF2 and other cytokines produced by human endometrial epithelial cells, providing a mechanism for enhancing endometrial receptivity. Hum Reprod 26:1153–1162CrossRefGoogle Scholar
- 33.Schumacher A, Brachwitz N, Sohr S, Engeland K, Langwisch S, Dolaptchieva M, Alexander T, Taran A, Malfertheiner SF, Costa SD, Zimmermann G, Nitschke C, Volk HD, Alexander H, Gunzer M, Zenclussen AC (2009) Human chorionic gonadotropin attracts regulatory T cells into the fetal-maternal interface during early human pregnancy. J Immunol 182:5488–5497CrossRefGoogle Scholar
- 35.Berndt S, Perrier DS, Blacher S, Pequeux C, Lorquet S, Munaut C, Applanat M, Herve MA, Lamande N, Corvol P, van den BF, Frankenne F, Poutanen M, Huhtaniemi I, Geenen V, Noel A, Foidart JM (2006) Angiogenic activity of human chorionic gonadotropin through LH receptor activation on endothelial and epithelial cells of the endometrium. FASEB J 20:2630–2632CrossRefGoogle Scholar
- 39.Fluhr H, Bischof-Islami D, Krenzer S, Licht P, Bischof P, Zygmunt M (2008) Human chorionic gonadotropin stimulates matrix metalloproteinases-2 and -9 in cytotrophoblastic cells and decreases tissue inhibitor of metalloproteinases-1, -2, and -3 in decidualized endometrial stromal cells. Fertil Steril 90:1390–1395CrossRefGoogle Scholar
- 44.Shoupe D, Mishell DR Jr, Lacarra M, Lobo RA, Horenstein J, d’Ablaing G, Moyer D (1989) Correlation of endometrial maturation with four methods of estimating day of ovulation. Obstet Gynecol 73:88–92Google Scholar
- 45.Ghosh D, Sengupta J (2014) Delineating the prime mover action of progesterone for endometrial receptivity in primates. Indian J Med Res 140(Suppl):S130–S136Google Scholar
- 49.Ziecik AJ, Recka-Reszka K, Rzucidlo SJ (1992) Extragonadal gonadotropin receptors, their distribution and function. J Physiol Pharmacol 43:33–49Google Scholar
- 57.Smith S (1992) Determining the time of the urinary luteinizing hormone surge. Does it facilitate the interpretation of endometrial biopsy results? J Reprod Med 37:785–788Google Scholar
- 58.Diaz-Gimeno P, Ruiz-Alonso M, Blesa D, Bosch N, Martinez-Conejero JA, Alama P, Garrido N, Pellicer A, Simon C (2013) The accuracy and reproducibility of the endometrial receptivity array is superior to histology as a diagnostic method for endometrial receptivity. Fertil Steril 99:508–517CrossRefGoogle Scholar
- 61.Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S (2011) Evidence of impaired endometrial receptivity after ovarian stimulation for in vitro fertilization: a prospective randomized trial comparing fresh and frozen-thawed embryo transfer in normal responders. Fertil Steril 96:344–348CrossRefGoogle Scholar
- 64.Schwalenberg T, Stolzenburg JU, Ho TP, Mallock T, Hartenstein S, Alexander H, Zimmermann G, Hohenfellner R, Denzinger S, Burger M, Horn LC, Neuhaus J (2011) Enhanced urothelial expression of human chorionic gonadotropin beta (hCGβ) in bladder pain syndrome/interstitial cystitis (BPS/IC). World J Urol 30:411–417CrossRefGoogle Scholar