A distinct cohort of the TGF superfamily members expressed in human endometrium regulate decidualization
Authors: Stoikos, Chelsea J.; Harrison, Craig A.; Salamonsen, Lois A.; Dimitriadis, Evdokia
Source: Human Reproduction, Volume 23, Number 6, 21 June 2008 , pp. 1447-1456(10)
Publisher: Oxford University Press
Abstract:BACKGROUNDSuccessful blastocyst implantation requires the differentiation of human endometrial stromal cells (HESC), a process known as decidualization. Activin A, a transforming growth factor (TGF) superfamily member, enhances HESC decidualization and localizes to decidual cells in human endometrium. Other TGF superfamily members, including BMP2, BMP4, BMP7, GDF5, GDF8, GDF11, TGFs and Nodal, may also play a role during decidualization. This study aimed to identify these TGF family members in human endometrium, and to determine whether they are involved in human decidualization.METHODSProtein localization of TGF family members was examined in secretory phase human endometrium and first trimester decidua by immunohistochemistry. mRNA expression was examined in HESC. Activin inhibitors (Activin-M108A/SB431542) with differing specificities for the other TGF members under consideration were applied during HESC decidualization in vitro. The secretion levels of potential TGF superfamily members were measured during decidualization, and recombinant proteins added to examine their effect.RESULTSThis study has identified BMP2, BMP4, BMP7, GDF5, GDF8 and GDF11 but not Nodal in secretory phase human endometrium, but only BMP2, GDF5 and TGF1 protein were detected in decidual cells. All ligands except Nodal were expressed by cultured HESC. Both inhibitors significantly reduced decidualization validating the role of activin, but potentially also other TGF members, during decidualization. BMP2 and TGF1 secretion increased during HESC decidualisation and exogenous administration of these proteins significantly enhanced decidualization in vitro.CONCLUSIONSLike activin, BMP2 and TGF1 are likely to be involved in HESC decidualization. This is the first study to identify and localize BMP4, BMP7, GDF5, GDF8 and GDF11 in secretory phase human endometrium. Understanding the factors critical for the implantation process is needed for improving fertility and pregnancy outcomes.
Document Type: Research article
Publication date: 2008-06-21
- Human Reproduction features full-length, peer-reviewed papers reporting original research, clinical case histories, as well as opinions and debates on topical issues. Papers published cover the scientific and medical aspects of reproductive physiology and pathology, endocrinology, andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues. The highest scientific and editorial standard is maintained throughout the journal along with a rapid rate of publication.