Decidualization is Impaired in Endometrial Stromal Cells from Uterine Rudiments in Mayer-Rokitansky-Küster-Hauser Syndrome

Abstract

Background/Aims: Uterine rudiments from patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) contain all tissues typically found in the uterus. Endometrium from the rudiments predominantly exhibits basalis-like features, and endometrial proliferative capacity in patients’ epithelium and stroma is significantly lower. Methods: This single-center, prospective study conducted at a major German university hospital compared in-vitro decidualization in cultured ESCs from MRKHS patients and hysterectomy controls. Primary ESC cultures were established from both sources. Hormone-induced prolactin and IGFBP-1 secretion served as a measure of their ability to undergo decidualization in response to hormonal stimulation. Expression levels of 8 key marker genes of decidualization were also determined. Results: At day 9, mean secretion of prolactin and IGFBP-1 was significantly reduced by 89.0% and 99.5%, respectively, in MRKHS ESCs vs. hysterectomy controls, both indicating impaired decidualization of MRKHS ESCs. Key decidual markers confirmed impaired decidualization in MRKHS patients. Conclusion: Our results indicate that the ESCs from MRKHS patients lack hormone responsiveness as a potential sign of dysfunctional hormone receptor function, which may also play a role in the onset of MRKHS. Further studies are needed to corroborate our findings, directly address receptor function, and elucidate the role of other potential determinants of uterine development and adult function.

The Endometrial Transcription Landscape of MRKH Syndrome

“…The analogous analysis for type 2 was omitted due to the highly skewed sample distribution with respect to cycle stages. Together, these analyses are in line with previous reports that the endometrium of MRKH patients does not respond correctly to cycle hormones ( Ludwig, 1998a , b ; Rall et al, 2013 ; Brucker et al, 2017 ).…”

“…Instead, the expression of most genes remained in the proliferative phase although the hormonal profiles indicate patients were in the secretory phase. This finding agrees with previous studies that describe lacking responsiveness of the endometrium to hormones in MRKH patients ( Ludwig, 1998a , b ; Rall et al, 2013 ; Brucker et al, 2017 ). The transcriptome data we provide now offer the opportunity to trace the phenomenon to individual genes and pathways and examine co-occurring effects.…”

The endometrial transcription landscape of MRKH syndrome

“…Instead, the expression of most genes remained in the proliferative phase although the hormonal profiles indicate patients were in the secretory phase. This finding agrees with previous studies that describe lacking responsiveness of the endometrium to hormones in MRKH patients (15)(16)(17)(18). The transcriptome data we provide now offer the opportunity to trace the phenomenon to individual genes and pathways and examine co-occurring effects.…”

“…The analogous analysis for type 2 was omitted due to the highly skewed sample distribution with respect to cycle stages. Together, these analyses are in line with previous reports that the endometrium of MRKH patients does not respond correctly to cycle hormones (15)(16)(17)(18).…”

FKBP51 promotes migration and invasion of papillary thyroid carcinoma through NF‑κB‑dependent epithelial‑to‑mesenchymal transition

“…It contains a 3-unit tetratricopeptide repeat structural motif connected to a domain that mediates enzymatic function and peptidyl prolyl isomerase activity. FKBP51 interacts with glucocorticoid, androgen, estrogen, progestin and mineralocorticoid receptors ( 2 – 7 ) through a number of components of the molecular chaperone machinery, including heat shock protein 90. FKBP51 has been identified to be upregulated or downregulated in multiple types of cancer and to be associated with cell motility and invasion, for instance, Leach et al ( 8 ) identified that FKBP51 is increased in prostate cancer cells compared with normal prostate epithelial cells and improves the ability of stromal androgen receptor to predict prostate cancer-specific mortality.…”