Mechanical stretch upregulates IGFBP-1 secretion from decidualized endometrial stromal cells

Abstract

Recently, uterine movement-induced mechanical stress was noticed to have possible effects on endometrial functions. In this study, we addressed the possible effect of mechanical stress on the process of decidualization of endometrial stromal cells (ESC). ESC were cultured on flexiblebottomed culture plates. After decidualization was achieved with estradiol and progesterone for 12 days, cultures were continued for 24 h with or without cyclic stretch (25% elongation) in serum-free conditions at a rate of 2 cycles/min using a computer-operated cell tension system. Concentrations of insulin-like growth factor-binding protein-1 (IGFBP-1), a marker of decidualization, in the conditioned medium were measured by specific ELISA, and IGFBP-1 mRNA expression in the ESC was measured by RT-PCR. Cyclic stretch remarkably increased IGFBP-1 secretion from decidualized ESC. It also increased IGFBP-1 mRNA in decidualized ESC. The increase in IGFBP-1 secretion was inhibited by actinomycin D but not by indomethacin, PD-98059, or H-89. Conditioned medium of decidualized ESC cultured with cyclic stretch increased IGFBP-1 secretion from decidualized ESC cultured under stationary conditions. These findings imply that uterine movement modulates decidualization of the endometrium and has a regulatory effect on reproduction.insulin-like growth factor-binding protein-1; endometrium; decidualization; prostaglandin E2; indometacin DECIDUALIZATION, a process of endometrial differentiation, is essential for embryo implantation and maintenance of pregnancy. During the process of decidualization, characteristics of endometrial cells change profoundly. This was demonstrated by marked alterations in the expression of numerous genes in decidualized human endometrial stromal cells (ESC) in vitro (17). Progesterone is a well-known inducer of decidualization, whereas prostaglandin E 2 (PGE 2 ) and relaxin enhance the process via activation of cAMP signaling (8,11,16,20). However, the complex mechanisms that regulates decidualization remains to be elucidated.Recently, uterine movement, a mechanical process, has been noticed to play important roles in fertility (4). Subendometrial myometrium exerts wave-like activity throughout the menstrual cycle (3, 13), and the movement is believed to support embryo and sperm transfer. The peristaltic uterine movement is also suggested to be involved in other uterus-related events such as endometriosis and menstruation. Recently, we (9) suggested that the subendometrial myometrial movement is transduced to a biochemical signal in the endometrium and may play roles in endometrium-related physiological and pathological events.Given that the mechanical stress associated with uterine peristalsis alters biochemical characteristics of the endometrium, it is plausible that decidualization, a differentiation process of the endometrium, may be affected by the uterine movement. To address the issue, we conducted an in vitro study to see the effect of mechanical stretch on the production of IGFBP-1, a representative marker of d...

Polymerization of insulin‐like growth factor‐binding protein‐1 (IGFBP‐1) potentiates IGF‐I actions in placenta

“…The hypothesis that the embryo‐maternal unit synthesizes considerable amounts of steroid hormones and that IGFBP‐1 and tissue transglutaminase are both controlled hormonally (Signorini et al, 1988; Lathi et al, 2005; Harada et al, 2006) prompted us to investigate the contribution of steroid hormones in regulating tissue transglutaminase‐induced IGFBP‐1 polymerization at feto‐maternal interface.…”

Current concepts of the pathogenesis of endometriosis

“…These findings indicate inhibitory properties of GnRH II against endometriosis. Thus, the lower expression of GnRH II in the eutopic endometrium of women with endometriosis may support the concept that endogenous GnRH II-mediated • Changes in eutopic uterine contraction [6,7] GnRHII [4] TRAIL/OPG [9,10] • Retrograde menstruation endometrium GnRHII…”

“…Mechanical stretch generally induces biochemical changes in cells, and thus it has been postulated that the mechanical stretch exerted by uterine movement stimulates the production of biochemical mediators in endometrial cells. To investigate the effects of mechanical stretch in the endometrium, we cultured endometrial stromal cells on flexible-bottomed culture plates, and cyclic stretch was applied in serum-free conditions using a computer-operated cell tension system [6,7]. Cyclic stretch was found to increase the gene expression and protein secretion of IL-8 from endometrial stromal cells.…”

“…• Changes in eutopic uterine contraction [6,7] GnRHII [4] TRAIL/OPG [9,10] • Retrograde menstruation endometrium GnRHII…”

Induction of early decidualization by cadmium, a major contaminant of cigarette smoke

“…Isolation and culture of human endometrial stromal cells and in vitro decidualization were achieved as described previously (4,5). Human endometrial stromal cells were treated with 2% charcoal-stripped fetal bovine serum in the presence of 10 nmol/L E 2 plus 1 mmol/L P in the presence or absence of CdCl 2 or 0.1% ethanol vehicle (control).…”