Coexpression of pinopodes and leukemia inhibitory factor, as well as its receptor, in human endometrium*1 (original) (raw)
Related papers
Fertility and Sterility, 2010
Objective: To determine whether the expression of leukemia inhibitory factor during the implantation window in endometrial tissue and uterine flushing fluid of patients with adenomyosis differs from that of healthy fertile women. Design: Experimental study using endometrial tissue and uterine flushing fluid. Setting: Peking University First Hospital, People's Republic of China. Patient(s): There were 28 patients with adenomyosis and 27 control fertile women. Intervention(s): Uterine flushing fluid and endometrial samples were collected during the implantation window, defined as 7 to 9 days after ovulation. Main Outcome Measure(s): Leukemia inhibitory factor levels in uterine flushing fluid were measured by enzymelinked immunosorbent assay. Leukemia inhibitory factor messenger RNA expression in eutopic endometrium was quantified by real-time reverse transcriptase polymerase chain reaction. Leukemia inhibitory factor protein expression was evaluated with semiquantitative immunohistochemistry. Result(s): Leukemia inhibitory factor levels were significantly lower in the uterine flushing fluid of patients with adenomyosis with a history of infertility. Leukemia inhibitory factor messenger RNA and protein also were significantly lower in patients with adenomyosis, compared with control. Leukemia inhibitory factor immunostaining intensity was significantly lower in patients with adenomyosis, compared with control. Conclusion(s): Leukemia inhibitory factor is dysregulated in the endometrium and uterine flushing fluid of women with adenomyosis during the implantation window. (Fertil Steril Ò 2010;94:85-9.
Medicina
Objective: To investigate morphological changes in the endometrial epithelial cells of patients with infertility problems. Materials and methods: Endometrial biopsies were obtained from 10 women who have undergone several unsuccessful in vitro fertilisation (IVF) procedures. Endometrial biopsies were performed between luteinizing hormone surge days LH+6 to +10 of the natural menstrual cycle. Each sample was divided into three parts, which were processed for histological, transmission (TEM), and scanning electron microscopy (SEM) investigations. Results: Histological investigations demonstrated significant alterations in the apical part of epithelial cells of one patient; in four patients, the gland maturity was low, not matching the cycle day, and thus a phase lag had developed. By TEM examination, we ascertained changes in secretory and ciliated cells in three patients (decreased amount or missing microvilli, irregular cilia in ciliated cells). SEM examination found pinopodes in fi...
The presence of pinopodes in the human endometrium does not delineate the implantation window
Fertility and Sterility, 2007
Objective: To assess pinopode formation in human endometrium during the luteal phase of the menstrual cycle and in the first trimester of pregnancy. Design: Prospective clinical study. Setting: Outpatient infertility clinics and outpatient family planning clinic. Patient(s): Thirty-two regularly cycling infertile women, 15 regularly cycling fertile women, 9 women receiving elective termination of pregnancy, and 1 woman receiving GnRH agonist and hormone therapy addback. Intervention(s): Endometrial tissue was collected by suction pipelle and examined by scanning electron microscopy for pinopode formation. Main Outcome Measure(s): Endometrial tissue was scored (0, 1, 2, 3, or 4) depending on the percentage of the surface covered in pinopodes (from 0% to Ͼ20% of 100 fields).
Pathogenic mechanisms in endometriosis-associated infertility
Fertility and Sterility, 2008
Objective: To review the mechanisms by which endometriosis may affect reproductive function. Design: Review of the English literature from 1986 to 2007 after searching Medline, EMBASE, Cochrane, and BIOSIS, as well as relevant meeting abstracts. Setting: Fertility research center and obstetrics and gynecology department in a tertiary care hospital. Result(s): There is compelling evidence in the literature that endometriosis has detrimental effects on ovarian and tubal function and uterine receptivity, resulting in female infertility. The mechanisms of infertility associated with endometriosis remain controversial and include abnormal folliculogenesis, elevated oxidative stress, altered immune function, and hormonal milieu in the follicular and peritoneal environments, and reduced endometrial receptivity. These factors lead to poor oocyte quality, impaired fertilization, and implantation. Conclusion(s): Through unraveling the mechanisms by which endometriosis leads to infertility, researchers are sure to find a nonsurgical means to diagnose endometriosis, most likely through serum and peritoneal markers. Cytokines, interleukins, oxidative stress markers, and soluble cellular adhesion molecules all show potential to be used as a reliable marker for diagnosing endometriosis. After analyzing the pathogenic mechanisms of endometriosis, it seems that the future treatment of this entity may include cyclo-oxygenase-2 inhibitors, immunomodulators, or hormonal suppressive therapy to eliminate the need for surgical treatment of endometriosis. (Fertil Steril Ò 2008;90:247-57.
Endometrial pinopodes indicate a shift in the window of receptivity in IVF cycles
Human Reproduction, 1999
The formation of endometrial pinopodes detected by scanning electron microscopy may be a specific marker for uterine receptivity. Aiming to assess the effects of ovarian stimulation on pinopode formation, we examined sequential endometrial biopsies from 17 oocyte donors. Seven normally menstruating women served as controls. Up to four samples were taken from each woman at 24-72 h intervals between days 14 and 24, giving a total of 69 samples. The day of oocyte retrieval was designated day 14 in ovarian stimulation cycles and the day of luteinizing hormone surge was designated day 13 in natural cycles. Endometrial morphology and pinopode numbers were similar in both groups. Fully developed pinopodes appeared in only one sample per cycle, indicating their short life span. However, the cycle day these structures appeared varied up to 5 days between women and the distribution was as follows: day 18 (n⍧2), day 19 (n⍧7), day 20 (n⍧4), day 21 (n⍧3), day 22 (n⍧1) in ovarian stimulation cycles, and day 20 (n⍧2), day 21 (n⍧2), day 22 (n⍧3) in natural cycles. Furthermore, accelerated pinopode formation in ovarian stimulation cycles was positively correlated with day 13 progesterone. Our findings show that ovarian stimulation does not affect endometrial pinopode formation in terms of quantity and life span. The cycle days when pinopodes form are specific to the individual, being on average 1-2 days earlier in ovarian stimulation than in natural cycles. These changes in pinopode expression may reflect shifts in the window of receptivity, resulting in ovo-endometrial asynchrony and limiting implantation success in in-vitro fertilization.
Fertility and Sterility, 2003
Objective: To assess the temporal and morphologic characteristics of pinopod expression on the surface of endometrium across the secretory phase, in LH-timed endometrial samples in normal, healthy women. Design: Prospective, randomized study. Setting: Academic teaching hospital. Patient(s): Sixty-eight healthy volunteers with proven fertility. Intervention(s): Urinary LH-timed endometrial and blood sampling was performed on each subject on a randomly selected day of the secretory phase. Main Outcome Measure(s): Histologic dating, assessment of pinopods using scanning electron microscopy, and comparison with serum P levels. Result(s): Eighty-six endometrial tissue samples obtained from 68 subjects were evaluated under scanning electron microscopy. Pinopods were first observed on luteal day 5, corresponding with the onset of the midluteal phase increase in serum P levels. Pinopods persisted for the entire duration of the secretory phase, but their morphology changed as the cycle advanced. Conclusion(s): The present findings demonstrate that pinopods are a characteristic feature of the mid to late secretory phase endometrial epithelium, exhibit cycle-dependent changes in morphology, and are most prominent during the putative implantation interval.
The effect of sperm activation on pinopod formation in endometrial epithelium
Journal of the Anatomical Society of India, 2016
Endometrial receptivity is crucial in implantation of the developing embryo in the endometrium and formation of the pregnancy. In this study, possible effect of sperm and uterine endometrial contact on formation of pinopod, an important element in morphological differentiation necessary for implantation, was investigated. Materials and methods: In this experimental study, 42 female Spraque-Dawley albino rats and 14 male Spraque-Dawley albino rats (total 56 rats) were used. Vasectomy was performed in half of the male rats. For each group, two distinct branches were formed with 21 females and 7 males: Group 1 (nonvasectomized) and Group 2 (vasectomized). Cases were sacrificed and evaluated every day from Day 1 to Day 3. Scanning electron microscopic (SEM) images were analyzed according to different stages of pinopod development on different days. Pinopods were classified as developing, developed and regressing pinopod. The average number of pinopods were calculated by counting the pinopods at four endometrial regions examined for each rat and total number was divided by 4. Same procedure was done for all rats in every group. Results were compared among the groups. For statistical analysis among the groups, *Independent Samples Test (Mean AE Std) and **Mann Whitney U Test (Median (25-75%)) were used. Results: The most important finding in SEM examination of uterus removed on the first day following mating from female rats that were copulated with non-vasectomy male rats which comprised the first group of the study was that heads of the sperms in the uterus were embedded in endometrial epithelium. Similarly, examination of the endometrium of uterus that were removed on postcoital second day revealed small number of developed pinopods (average 0.39) (P = 0.902). Examination was done by taking the developing pinopods within image area into account and number of developing pinopods in endometrium epithelium of the rats in first group (average 20.61) was higher than that of second group (average 12.86) (P < 0.001). Examination of endometrium of the uterus that were removed on third postcoital day revealed less number of developing pinopods in both groups. Examination of first group revealed an average of 1.21 developing pinopod, whereas the average number of developing pinopod in second group was 2.25 (P = 0.011). Examination based on the count of developed pinopods revealed that number of pinopods in first group (average 13.79) was higher than second group (average 8.96) (P < 0.001). Regressing pinopod images were observed in only endometrium that were taken on postcoital third day in the second group. Conclusion: In this study, it was clearly shown that sperms were entered into endometrial epithelium with their heads. It can be suggested that they might have a facilitating effect for pinopod formation by reacting with endometrial epithelium as a result of this invasion. It would be beneficial to demolish the other factors triggering pinopod formation to investigate whether presence of sperm alone in the uterus has an effect on pinopod formation.
Fertility and Sterility, 2009
Objective: To investigate lipopolysaccharide (LPS)-induced DNA damage in preimplanting embryonic and uterine cells during preimplantation period of pregnancy that may ultimately inhibit the process of implantation in mouse. Design: Animal study. Setting: Academic research environment. Animal(s): Sixty four Park strain female mice. Intervention(s): The ''minimum dose'' (MD) of LPS was injected intraperitoneally in the pregnant females on day 0.5 of pregnancy, and individual embryos and uterine cells were assessed by comet assay on days 1.5, 2.5, 3.5, and 4.375 of the preimplantation period of pregnancy. Main Outcome Measure(s): Percentage of embryos and uterine cells with tail, mean comet tail length, percentage of fragmented DNA in tail. Result(s): Significantly higher numbers of embryos with higher mean comet tail length and percentage of fragmented DNA in tail were observed in the LPS-treated compared with control animals as the period of pregnancy approaches the stage of implantation. At the same time, DNA damage was also significantly higher in the uterine cells of LPS-treated compared with control animals. Conclusion(s): The MD of LPS can induce DNA damage in the preimplantation-stage embryos and uterine cells, which causes poor embryonic development and improper preparation of uterine horns during the preimplantation period of pregnancy, which may ultimately inhibit the process of implantation in mouse. (Fertil Steril Ò 2009; 91:2095-103. Ó2009 by American Society for Reproductive Medicine.
BMC Women's Health, 2012
Background: Uterine receptivity and implantation are complex processes requiring coordinated expression of molecules by zygote and uterus. Our objective was to evaluate the role of the endometrial expression of leukemia inhibitory factor (LIF) and its glycoprotein 130 (gp130) receptor molecules and their secretion in uterine flushing during the window of implantation in cases of primary unexplained infertility Case presentation: The study was conducted on 25 infertile women with unexplained infertility for at least two years and 10 normal fertile women as a control group . Endometrial tissue and uterine flushing were obtained. Each tissue specimen was divided into two pieces; one piece was used for histological dating of the endometrium and for immunostaining of progesterone receptors, and the second was used for RNA extraction and PCR assay of LIF and gp130 mRNA expression. Serum estrogen and progesterone were measured for all subjects. LIF mRNA was expressed in the endometrium of all normal fertile women but significantly decreased in infertile women. LIF was not detectable in 88% of infertile women while it was fairly detectable in 12% of them. Gp130 mRNA was hardly detectable in both fertile and infertile women with no difference between them. Infertile women secreted significantly less LIF and gp130 molecules in the uterine flushing compared with normal fertile women. Conclusions: Expression of LIF mRNA in endometrium could be used as a molecular marker of unexplained infertility. Assessment of secreted LIF and gp130 molecules in uterine flushing could be another useful and safe method for predicting successful implantation as well as for diagnosing and eventually treating women with impaired fertility using recombinant human LIF.