Leukemia Inhibitory Factor In Endometrium Research Articles

Effects of bone marrow mesenchymal stem cells on repair and receptivity of damaged endometrium in rats.

This study was to investigate whether bone marrow mesenchymal stem cells (BMSCs) can repair damaged endometrium in rats and its effect on endometrial receptivity. A rat model of endometrial damage was established by heat injury. BMSCs were labeled with PKH26 and were transplanted into the right uterine cavity. The endometrial thickness and fertility testing were examined to assess the repair of damaged endometrium. The mass on trichrome staining was used to assess the endometrium fibrosis. The expression of integrin avβ3 and leukemia inhibitory factor (LIF) in rat endometrium was used to evaluate the endometrial receptivity. After transplantation of BMSCs, the distribution of PKH26 positive cells was mainly on the damaged side in the endometrial tissues. Compared to control group, the endometrial tissue structure recovered after treatment with BMSCs. BMSCs transplantation improved the fertility of endometrial injury model rats. BMSCs decreased the area of endometrial fibrosis. The expression of integrin avβ3 and LIF in endometrium was the stronger in BMSCs treatment group than control group. BMSCs can migrate to the endometrium and repair damaged endometrium and improve endometrium receptivity.

Effects of modified Shoutaiwai recipe on integrin β3 and leukemia-inhibitory factor in endometrium of controlled ovarian hyperstimulation mice during the implantation window.

We investigated the effects of a modified Shoutaiwai recipe on integrin β3 and leukemia-inhibitory factor (LIF) in the endometrium of controlled ovarian hyperstimulation (COH) mice during the implantation window. Seventy non-pregnant mice were randomly divided into 3 groups: a traditional medicine (TCM) treatment group (N = 30), an aspirin treatment (N = 30) group, and a control group (N = 10). After the model was successfully established, mice in the drug treatment groups and the control group were respectively treated with the modified Shoutaiwai recipe, aspirin, or 0.9% physiological saline. During the implantation window of mice, the middle segment of the mouse uterus was recovered, and integrin β3 and LIF expressions in the endometrium were respectively detected using an immunohistological two-step method and reverse transcription-PCR. Expressions of integrin β3 and LIF in the endometrium of mice in the TCM treatment group were significantly increased compared to aspirin-treated and control mice, and those of aspirin-treated mice were increased compared to the control group. Our modified Shoutaiwai recipe may improve the endometrial receptivity of COH mice by increasing the expression of integrin β3 and LIF in the endometrium during the implantation window.

The low expression of leukemia inhibitory factor in endometrium: Possible relevant to unexplained infertility with multiple implantation failures

Unexplained infertility affects 25% of infertile couples. Cytokines and growth factors have been suggested to play an important role in the initial process of successful implantation in humans and failures in their production may be a cause of unexplained infertility. Leukemia inhibitory factor (LIF) and Interleukin-6 (IL-6) have demonstrated their importance in implantation in both animal and human studies. Lower expression of LIF is found in proliferative phase and maximal expression is found in secretory phase of the menstrual cycle. Lower expression of LIF is also found in secretory phase endometrium in patients with infertility. However, studies investigating whether the levels of LIF in proliferative phase are associated with multiple implantation failures (MIFs) are limited. 30 Endometrial biopsies in proliferative phase from unexplained infertile women with MIF with normal hormone levels were collected. The expression of LIF, IL-6 and its receptor gp130 were measured by immunohistochemistry and western blotting. Moderate expression of LIF in the proliferative phase and high expression of LIF in the secretory phase were found in fertile women. However, lower expression of LIF was found in unexplained infertile women with MIF compared to fertile women. There was no difference in endometrial IL-6 and gp130 expression between unexplained infertile women with MIF and fertile women. LIF expression is independent of the process of embryo and dependent partially on the maternal sex hormone levels. Our data suggest that the initial lower expression of LIF in proliferative phase may be one of the causes for multiple failure of implantation.

Immunolocalisation of phosphorylated STAT3, interleukin 11 and leukaemia inhibitory factor in endometrium of women with unexplained infertility during the implantation window.

BackgroundUterine receptivity and embryo implantation are critical in the establishment of pregnancy. The diagnosis of endometrial fertility requires more precise measurements of endometrial receptivity. Interleukin (IL-11) and leukemia inhibitory factor (LIF) are essential for murine implantation and signal via intracellular phosphorylation (p) of STAT3 in the endometrium. Both cytokines are present in the endometrium of women duiring the receptive window. Endometrial IL-11, IL-11 receptor alpha (IL-11Ralpha), LIF and pSTAT3 in women with primary unexplained infertility was compared to normal fertile women during the implantation window.MethodsLH timed endometrial biopsies (LH+6 to LH+10) were collected from women with unexplained infertility and normal fertility. pSTAT3, IL-11, IL-11Ralpha and LIF production was determined by immunohistochemistry. Staining intensity was determoned by two independent observers blind to the fertility status of the patient from whom the biopsy was taken. Staining intensity and heterogeneity in each of the endometrial compartments (epithelium; stroma, including decidualized stromal cells; and vasculature) was assessed. The Mann-Whitney U test was used to analyze IL-11, pSTAT3, IL-11Ralpha and LIF immunostaining intensities in the samples.ResultsIL-11, IL-11Ralpha and LIF were present predominantly in glandular epithelium, whilst luminal epithelium showed patchy staining. pSTAT3 was present in both glandular epithelium and stroma. IL-11 and pSTAT3 immunostaining was significantly lower in glandular epithelium in infertile women compared to controls (P < 0.05) whilst IL-11Ralpha and LIF staining did not differ.ConclusionThis is the first demonstration of reduced endometrial pSTAT3 and IL-11 in some women with unexplained infertility. This suggests IL-11 and pSTAT3 may be involved in the secretory transformation of glandular epithelium during receptivity. Reduced IL-11 production and STAT3 phosphorylation may contribute to unexplained infertility in some women.

Leukaemia inhibitory factor in endometrium during the oestrous cycle, early pregnancy and in ovariectomized steroid-treated ewes.

Leukaemia inhibitory factor (LIF), a pleiotropic cytokine, is essential for blastocyst implantation in mice and maintains the development of ovine embryos in culture. The expression of LIF was examined by northern blot analysis in endometrial tissue from cyclic (days 4-16) and pregnant (days 4-20) ewes, and the corresponding protein was immunolocalized. Expression of mRNA encoding LIF remained relatively constant throughout the oestrous cycle and was present during early pregnancy. A decrease in mRNA encoding LIF was observed during early pregnancy (on days 12-14) and expression was highest on days 16-20. Immunoreactive LIF was present in the cellular compartments of the endometrium throughout the oestrous cycle and early pregnancy, with maximal immunostaining in the caruncular and intercaruncular luminal epithelium, and moderate staining in the glandular epithelium and intercaruncular stroma. Immunoreactive LIF was also detected in the trophoblast cells of day 17 blastocysts. Separately cultured endometrial epithelial and stromal cells from pregnant animals both expressed mRNA encoding LIF. Ovariectomized steroid-treated ewes were studied to establish whether steroid hormones had a role in regulating endometrial LIF. Ewes treated with oestradiol alone showed lower concentrations of immunoreactive LIF in the endometrium in comparison to ovariectomized, control animals, while treatment of ovariectomized animals with both oestradiol and progesterone had a greater inhibitory effect on LIF immunolocalization. These studies demonstrate the presence of mRNA encoding LIF and protein throughout the oestrous cycle and early pregnancy and suggest that steroid hormones may be involved in their regulation.

Modulation of leukemia inhibitory factor gene expression and protein biosynthesis in human endometrium.

Implantation is the process by which the blastocyst becomes intimately connected with the maternal endometrium/decidua. The independently developing preimplantation blastocyst then becomes dependent on the maternal environment for its continued development. Although the factors involved in the regulation of blastocyst implantation are incompletely understood, recent studies strongly suggest a critical role for leukemia inhibitory factor (LIF) in mice. We showed previously that LIF acts on human trophoblasts to shift their differentiation toward the anchoring phenotype by increasing the synthesis of fibronectin. In the present study, we first evaluated the temporal expression of LIF in the human endometrium in order to gain further insights into the role of LIF in human implantation. We established the LIF is expressed in the endometrium in a menstrual cycle-dependent manner. The most abundant LIF messenger ribonucleic acid (mRNA) levels are observed in the mid- and late-luteal phase samples. LIF mRNA was also present in decidual tissues of first trimester of pregnancy, but levels were lower than those found in the midluteal endometrium. We then investigated the regulation of LIF expression in human endometrial cells in culture by cytokines, steroid hormones, and growth factors. We could not show any direct stimulatory evidence of steroid hormones (estradiol and progestins) on LIF mRNA expression or protein production by endometrial cells in culture. On the other hand, we showed that interleukin-1, tumor necrosis factor-alpha, platelet-derived growth factor, epidermal growth factor, and transforming growth factor-beta are potent inducers of LIF expression in endometrial stromal cells in culture in a concentration- and time-dependent manner. Interferon-gamma acted to inhibit LIF expression induced by these cytokines. In contrast, we found high constitutive and relatively less regulated levels of LIF mRNA in the endometrial gland cells. The timing of the expression of LIF in the endometrium suggests a potential role in the implantation. The regulation of the expression of LIF may have an important role in the physiological and pathological processes involving human implantation.