Endometrial CRH and implantation: from bench to bedside

review OA: closed CC0 ⤵ 1 in-corpus citation
AI-generated summary by gemini-2.5-flash-lite+body, 2026-06-13

This review summarizes evidence on endometrial CRH in physiology and pathophysiology, highlighting its role in improving pregnancy rates for women with recurrent implantation failure.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

AI-generated deep summary by claude@2026-06, 2026-06-13 · read from full text

This review examines endometrial corticotropin-releasing hormone (CRH) in endometrial physiology and pathophysiology, integrating evidence on CRH’s roles in decidualisation and maternal–fetal immunotolerance and describing deregulated CRH expression as linked to chronic inflammatory reproductive disorders. It also highlights recent clinical data reporting that CRH can improve clinical pregnancy rates in women with repeated implantation failure after IVF and embryo transfer. A major caveat is that, as a narrative review, it synthesizes heterogeneous preclinical and clinical evidence rather than providing new mechanistic experiments or a single study’s controlled causal test. The paper relates to endometriosis and adenomyosis by explicitly citing deregulated CRH expression as associated with these conditions and including endometriosis- and adenomyosis-relevant CRH/urosspecific and inflammatory findings within its discussion. This paper is centrally about endometriosis — it discusses CRH deregulation in endometriosis and adenomyosis in the context of endometrial inflammatory disorders.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

Endometrial corticotropin-releasing hormone (CRH) has been described as a mediator of decidualisation and as a contributor of maternal-fetal immunotolerance. Deregulation of the CRH expression pattern has been associated with unfavourable reproductive outcomes as well as chronic endometrium-derived inflammatory disorders, such as endometriosis and adenomyosis. The current review summarises the evidence produced regarding the role of CRH in endometrial physiology and pathophysiology and highlights recent clinical data regarding the role of CRH in improving clinical pregnancy rates in women with repeated implantation failures following in vitro fertilisation and embryo transfer.
Full text 7,819 characters · extracted from oa-doi-fallback · 2 sections · click to expand

Abstract

Endometrial corticotropin-releasing hormone (CRH) has been described as a mediator of decidualisation and as a contributor of maternal–fetal immunotolerance. Deregulation of the CRH expression pattern has been associated with unfavourable reproductive outcomes as well as chronic endometrium-derived inflammatory disorders, such as endometriosis and adenomyosis. The current review summarises the evidence produced regarding the role of CRH in endometrial physiology and pathophysiology and highlights recent clinical data regarding the role of CRH in improving clinical pregnancy rates in women with repeated implantation failures following in vitro fertilisation and embryo transfer. Similar content being viewed by others

References

Chrousos GP (2009) Stress and disorders of the stress system. Nat Rev Endocrinol 5:374–381 Kalantaridou SN, Zoumakis E, Makrigiannakis A, Lavasidis LG, Vrekoussis T, Chrousos GP (2010) Corticotropin-releasing hormone, stress and human reproduction: an update. J Reprod Immunol 85:33–39 Makrigiannakis A, Margioris AN, Le Goascogne C et al (1995a) Corticotropin-releasing hormone (CRH) is expressed at the implantation sites of early pregnant rat uterus. Life Sci 57:1869–1875 Makrigiannakis A, Zoumakis E, Margioris AN, Theodoropoulos P, Stournaras C, Gravanis A (1995b) The corticotropin-releasing hormone (CRH) in normal and tumoral epithelial cells of human endometrium. J Clin Endocrinol Metab 80:185–189 Mastorakos G, Scopa CD, Kao LC et al (1996) Presence of immunoreactive corticotropin-releasing hormone in human endometrium. J Clin Endocrinol Metab 81:1046–1050 Di Blasio AM, Pecori Giraldi F, Vigano P, Petraglia F, Vignali M, Cavagnini F (1997) Expression of corticotropin-releasing hormone and its R1 receptor in human endometrial stromal cells. J Clin Endocrinol Metab 82:1594–1597 Ferrari A, Petraglia F, Gurpide E (1995) Corticotropin releasing factor decidualizes human endometrial stromal cells in vitro. Interaction with progestin. J Steroid Biochem Mol Biol 54:251–255 Kalantaridou SN, Zoumakis E, Weil S, Lavasidis LG, Chrousos GP, Makrigiannakis A (2007) Reproductive corticotropin releasing hormone, implantation, and fetal immunotolerance. Crit Rev Clin Lab Sci 44:461–481 Makrigiannakis A, Margioris AN, Chatzaki E, Zoumakis E, Chrousos GP, Gravanis A (1999) The decidualizing effect of progesterone may involve direct transcriptional activation of corticotrophin-releasing hormone from human endometrial stromal cells. Mol Hum Reprod 5:789–796 Hillhouse EW, Grammatopoulos D, Milton NG, Quartero HW (1993) The identification of a human myometrial corticotropin-releasing hormone receptor that increases in affinity during pregnancy. J Clin Endocrinol Metab 76:736–741 Bamberger AM, Schulte HM, Thuneke I, Erdmann I, Bamberger CM, Asa SL (1997) Expression of the apoptosis-inducing Fas ligand (FasL) in human first and third trimester placenta and choriocarcinoma cells. J Clin Endocrinol Metab 82:3173–3175 Makrigiannakis A, Zoumakis E, Kalantaridou S et al (2001) Corticotropin-releasing hormone promotes blastocyst implantation and early maternal tolerance. Nat Immunol 2:1018–1024 Bamberger AM, Minas V, Kalantaridou SN et al (2006) Corticotropin-releasing hormone modulates human trophoblast invasion through carcinoembryonic antigen-related cell adhesion molecule-1 regulation. Am J Pathol 168:141–150 Minas V, Jeschke U, Kalantaridou SN et al (2007a) Abortion is associated with increased expression of FasL in decidual leukocytes and apoptosis of extravillous trophoblasts: a role for CRH and urocortin. Mol Hum Reprod 13:663–673 Saito S, Nakashima A (2014) A review of the mechanism for poor placentation in early-onset preeclampsia: the role of autophagy in trophoblast invasion and vascular remodeling. J Reprod Immunol 101-102:80–88 Petsas G, Jeschke U, Richter DU et al (2012) Aberrant expression of corticotropin-releasing hormone in pre-eclampsia induces expression of FasL in maternal macrophages and extravillous trophoblast apoptosis. Mol Hum Reprod 18:535–545 Novembri R, Borges LE, Carrarelli P et al (2011) Impaired CRH and urocortin expression and function in eutopic endometrium of women with endometriosis. J Clin Endocrinol Metab 96:1145–1150 Vergetaki A, Jeschke U, Vrekoussis T et al (2013) Differential expression of CRH, UCN, CRHR1 and CRHR2 in eutopic and ectopic endometrium of women with endometriosis. PLoS One 8:e62313 Vergetaki A, Jeschke U, Vrekoussis T et al (2014) Galectin-1 overexpression in endometriosis and its regulation by neuropeptides (CRH, UCN) indicating its important role in reproduction and inflammation. PLoS One 9:e114229 Carrarelli P, Luddi A, Funghi L et al (2016) Urocortin and corticotrophin-releasing hormone receptor type 2 mRNA are highly expressed in deep infiltrating endometriotic lesions. Reprod BioMed Online 33:476–483 Vannuccini S, Tosti C, Carmona F et al (2017) Pathogenesis of adenomyosis: an update on molecular mechanisms. Reprod BioMed Online 35:592–601 Carrarelli P, Yen CF, Funghi L et al (2017) Expression of inflammatory and neurogenic mediators in adenomyosis. Reprod Sci 24:369–375 Minas V, Rolaki A, Kalantaridou SN et al (2007b) Intratumoral CRH modulates immuno-escape of ovarian cancer cells through FasL regulation. Br J Cancer 97:637–645 Taliouri E, Vrekoussis T, Vergetaki A, Agorastos T, Makrigiannakis A (2013) Corticotropin-releasing hormone (CRH) is expressed in the human cervical carcinoma cells (HeLa) and upregulates the expression of Fas ligand. Tumour Biol 34:125–130 Graziani G, Tentori L, Portarena I et al (2002) CRH inhibits cell growth of human endometrial adenocarcinoma cells via CRH-receptor 1-mediated activation of cAMP-PKA pathway. Endocrinology 143:807–813 Miceli F, Ranelletti FO, Martinelli E et al (2009) Expression and subcellular localization of CRH and its receptors in human endometrial cancer. Mol Cell Endocrinol 305:6–11 Sato N, Takagi K, Suzuki T et al (2014) Immunolocalization of corticotropin-releasing hormone (CRH) and its receptors (CRHR1 and CRHR2) in human endometrial carcinoma: CRHR1 as a potent prognostic factor. Int J Gynecol Cancer 24:1549–1557 Polanski LT, Baumgarten MN, Quenby S, Brosens J, Campbell BK, Raine-Fenning NJ (2014) What exactly do we mean by ‘recurrent implantation failure’? A systematic review and opinion. Reprod BioMed Online 28:409–423 Simon A, Laufer N (2012) Repeated implantation failure: clinical approach. Fertil Steril 97:1039–1043 Barash A, Dekel N, Fieldust S, Segal I, Schechtman E, Granot I (2003) Local injury to the endometrium doubles the incidence of successful pregnancies in patients undergoing in vitro fertilization. Fertil Steril 79:1317–1322 Gnainsky Y, Granot I, Aldo PB et al (2010) Local injury of the endometrium induces an inflammatory response that promotes successful implantation. Fertil Steril 94:2030–2036 Yoshioka S, Fujiwara H, Nakayama T, Kosaka K, Mori T, Fujii S (2006) Intrauterine administration of autologous peripheral blood mononuclear cells promotes implantation rates in patients with repeated failure of IVF-embryo transfer. Hum Reprod 21:3290–3294 Makrigiannakis A, BenKhalifa M, Vrekoussis T, Mahjub S, Kalantaridou SN, Gurgan T (2015) Repeated implantation failure: a new potential treatment option. Eur J Clin Investig 45:380–384 Author information Authors and Affiliations Corresponding author Ethics declarations Conflict of interest The authors declare that they have no conflict of interest. Rights and permissions About this article Cite this article Makrigiannakis, A., Vrekoussis, T., Zoumakis, E. et al. Endometrial CRH and implantation: from bench to bedside. Hormones 17, 293–297 (2018). https://doi.org/10.1007/s42000-018-0042-4 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s42000-018-0042-4

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

MeSH descriptors

Corticotropin-Releasing Hormone Embryo Implantation Embryo Transfer Endometrium Fertilization in Vitro Uterine Diseases Corticotropin-Releasing Hormone Embryo Implantation Endometrium Endometrium Endometrium Female Humans Uterine Diseases Uterine Diseases

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (33)

Cited by (1)

Source provenance

europepmc
last seen: 2026-08-14T06:11:53.302379+00:00
openalex
last seen: 2026-06-04T00:00:01.174412+00:00
pubmed
last seen: 2026-05-13T22:19:43.094626+00:00
unpaywall
last seen: 2026-08-14T06:25:32.811723+00:00
License: CC0 · commercial use OK