Endometrial receptivity has become the main cause of fertilization and pregnancy outcomes in infertile patients,bringing large psychological damage and economic loss to the patients and their family. In recent years,the role of non-coding RNA has increasingly been recognized. The relationship between non-coding RNA and endometrial receptivity is reviewed in this article.
Embryo Implantation ; Endometrium ; physiology ; Female ; Fertilization in Vitro ; Humans ; Pregnancy ; Pregnancy Outcome ; RNA, Untranslated ; genetics

OBJECTIVE: To observe the repairing effects of estrogen and wheat-grain moxibustion on thin-type endometrium in rats and to explore its possible mechanism. METHODS: Forty healthy SPF-grade adult female SD rats were randomly divided into a normal group, a model group, an estrogen group and a moxibustion group according to random number table method, 10 rats in each group. The model of thin-type endometrium was established during estrous period in all the groups except for the normal group. No intervention was given in the normal group. The intragastric administration of 2 mL of 0.9% sodium chloride solution was applied the next day after modeling in the model group. The intragastric administration of 2 mL of estradiol was given the next day after modeling in the estrogen group. The wheat-grain moxibustion was given at "Guanyuan" (CV 4) and "Shenshu" (BL 23) the next day after modeling in the moxibustion group, 7 moxa cones for each acupoint. The treatment in 3 groups was given once a day. After three estrous cycles, the samples were collected during estrous period; the thickness and morphology of endometrium were observed by HE staining; the expressions of vimentin, keratin and vascular endothelial growth factor (VEGF) in endometrium tissue were detected by immunohistochemistry; the expressions of HOXA10 and LIF in endometrium tissue were detected by Western blot. RESULTS: The endometrial thickness in the model group was significantly thinner than that in the normal group (<0.01); compared with the model group, the endometrial thickness in the estrogen group and the moxibustion group were increased significantly (<0.05, <0.01); the endometrial thickness in the moxibustion group was insignificantly higher than that in the estrogen group (>0.05). The expressions of keratin, vimentin and VEGF in endometrium in the model group were significantly lower than those in the normal group (<0.01); compared with the model group, the expressions of keratin, vimentin and VEGF in endometrium in the estrogen group and the moxibustion group were significantly increased (<0.01). The expressions of keratin, vimentin and VEGF in the moxibustion group were insignificantly higher than those in the estrogen group (>0.05). The expressions of HOXA10 and LIF in endometrium in the model group were significantly lower than those in the normal group (<0.01); compared with the model group, the expressions of HOXA10 and LIF in endometrium in the estrogen group and moxibustion group were significantly increased (<0.05). CONCLUSION The wheat-grain moxibustion could up-regulate the expressions of keratin, vimentin and VEGF in endometrium to improve the endometrial thickness; in addition, it could increase the levels of factors related to endometrial receptivity including HOXA10, LIF, which improves endometrial receptivity and play a repair role.
Animals ; Endometrium ; physiology ; Female ; Moxibustion ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Triticum ; Vascular Endothelial Growth Factor A

Stem cells are undifferentiated cells capable of self-renewal and differentiation into various cell lineages. Stem cells are responsible for the development of organs and regeneration of damaged tissues. The highly regenerative nature of the human endometrium during reproductive age suggests that stem cells play a critical role in endometrial physiology. Bone marrow-derived cells migrate to the uterus and participate in the healing and restoration of functionally or structurally damaged endometrium. This review summarizes recent research into the potential therapeutic effects of bone marrow-derived stem cells in conditions involving endometrial impairment.
Bone Marrow ; Cell Lineage ; Endometrium* ; Female ; Humans ; Physiology ; Regeneration* ; Stem Cells* ; Therapeutic Uses ; Uterus

BACKGROUNDAt present, a diagnostic tool with high specificity for impaired endometrial receptivity, which may lead to implantation failure, remains to be developed. We aimed to assess the different endometrial microRNA (miRNA) signatures for impaired endometrial receptivity by microarray analysis.

METHODSA total of 12 repeated implantation failure (RIF) patients and 10 infertile patients, who conceived and delivered after one embryo transfer attempt, were recruited as RIF and control groups, respectively. Endometrial specimens from the window of implantation (WOI) were collected from these two groups. MiRNA microarray was conducted on seven and five samples from the RIF and control groups, respectively. Comparative, functional, and network analyses were performed for the microarray results. Quantitative real-time polymerase chain reaction (PCR) was performed on other samples to validate the expression of specific miRNAs.

RESULTSCompared with those in the control group, the expression levels of 105 miRNAs in the RIF group were found to be significantly up- or down-regulated (at least 2-fold) by microarray analysis. The most relevant miRNA functional sets of these dysregulated miRNAs were miR-30 family, human embryonic stem cell regulation, epithelial-mesenchymal transition, and miRNA tumor suppressors by tool for annotations of microRNA analysis. Network regulatory analysis found 176 miRNA-mRNA interactions, and the top 3 core miRNAs were has-miR-4668-5p, has-miR-429, and has-miR-5088. Expression levels of the 18 selected miRNAs in new samples by real-time PCR were found to be regulated with the same trend, as the result of microarray analysis.

CONCLUSIONSThere is a significant different expression of certain miRNAs in the WOI endometrium for RIF patients. These miRNAs may contribute to impaired endometrial receptivity.

Adult ; Embryo Implantation ; genetics ; physiology ; Endometrium ; metabolism ; Female ; Humans ; Infertility, Female ; genetics ; MicroRNAs ; genetics ; Microarray Analysis ; Pregnancy ; Real-Time Polymerase Chain Reaction

OBJECTIVETo investigate the role of endometrial macrophages in embryo implantation and in regulating the expression of vascular endothelial growth factor A (VEGFA) in mouse endometrium during the peri-implantation period.

METHODAt D3.5 (D0.5 defined as the morning when a vaginal plug was observed), pregnant mice were divided randomly into experimental group, control group and blank group. In the experimental group, the mice were subjected to intrauterine injection of clodronate liposomes on the left side of uterus to eliminate the macrophages, and PBS liposomes on the right side. PBS liposomes and PBS were administered in the control and blank groups, respectively. The uterine tissues were collected on D5.5 and stained with trypan blue to show the implantation sites. Flow cytometry was performed to examine the percentage of F4/80(+) CD11b(+) macrophages macrophages in the uterus. F4/80(+) macrophage population within the endometrium and ovary and changes in VEGFA expression at the implantation and non-implantation sites were examined using immunohistochemistry.

RESULTSEndometrial F4/80(+) CD11b(+) macrophages macrophages were significantly reduced by 74% following intrauterine injection of clodronate liposomes (P<0.05). The number of macrophages in the ovaries showed no significant difference among the 3 groups. In the experimental group, the left side of the uterine showed imcomplete cavity closure with a lower number of implantation site than the right side (2.20∓1.81 vs 5.10∓1.91, P<0.05). VEGFA expression at the implantation site were significantly decreased in the endometrium on the left side with macrophage suppression as compared with that on the right side (P<0.05).

CONCLUSIONEndometrial macrophages appear to modulate uterine receptivity by regulating the expression of VEGFA to affect embryo implantation, suggesting the important role of macrophages in embryo implantation.

Animals ; Embryo Implantation ; Endometrium ; physiology ; Female ; Immunohistochemistry ; Macrophages ; cytology ; Mice ; Ovary ; cytology ; Pregnancy ; Random Allocation ; Uterus ; cytology ; Vascular Endothelial Growth Factor A ; physiology

Tight junctions (TJs) form continuous intercellular contacts in intercellular junctions. TJs involve integral proteins such as occludin (OCLN) and claudins (CLDNs) as well as peripheral proteins such as zona occludens-1 (ZO-1) and junctional adhesion molecules (JAMs). TJs control paracellular transportation across cell-to-cell junctions. Although TJs have been studied for several decades, comparison of the transcriptional-translational levels of these molecules in canine organs has not yet been performed. In this study, we examined uterine expression of CLDNs, OCLN, junction adhesion molecule-A, and ZO-1 in canine. Expression levels of canine uterine TJ proteins, including CLDN1, 2, 4, 5, JAM-A, ZO-1, and OCLN, were measured using reverse transcription PCR, real-time PCR, and Western blotting, whereas TJs distribution was determined by immunohistochemistry. The mRNA and protein expression levels of OCLN, CLDN-1, 4, JAM-1, and ZO-1 were identified in the uterus. Immunohistochemistry demonstrated that TJs were localized to the endometrium and/or myometrium of the uterus. Our results show that canine TJ proteins, including CLDNs, OCLN, JAM-A, and ZO-1, were expressed in the canine uterus. Taken together, these proteins may perform unique physiological roles in the uterus. Therefore, these findings may serve as a basis for further studies on TJ proteins and their roles in the physiological or pathological condition of the canine uterus.
Animals ; Blotting, Western ; Claudins ; Dogs ; Endometrium ; Female ; Herpes Zoster ; Immunohistochemistry ; Intercellular Junctions ; Junctional Adhesion Molecules ; Mice ; Myometrium ; Occludin ; Physiology ; Polymerase Chain Reaction ; Real-Time Polymerase Chain Reaction ; Reverse Transcription ; RNA, Messenger ; Tight Junctions* ; Transportation ; Uterus*

The aim of this study was to investigate the effect of Bu-Shen-An-Tai recipe (BSATR) and its two components (Bushen recipe, and Huoxue recipe) on endometrial morphology during peri-implantation in superovulated mice. Mice were randomly divided into five groups, including the normal (N), model (M), Bushen (BS), Huoxue (HX) and Bu-Shen-An-Tai (BH) groups. The uteri were collected on day 4 of pregnancy, and the endometrium thickness, microvessel density (MVD) and number of pinopodes observed. Compared with the M group, the endometrial thickness in the BS, HX and BH groups was significantly increased and there was a significant difference in endometrial thickness between the BS and the BH groups. The mean MVD was significantly lower in the M group than in the N group, and there was a significant increase in MVD in the BS, HX and BH groups as compared with the M group. Compared with the M group, the pinopode scores in the endometrium were significantly increased in the HX and BH groups; and the BS group had significantly higher pinipode scores than the HX and BH groups. In conclusion, the results of the present study demonstrated that the recipes (Bushen, Huoxue and BSATR) could improve the endometrial environment by regulating the endometrial thickness, MVD and the number of pinopodes at the window of implantation. Moreover, the Huoxue recipe and the BSATR were more efficient than the Bushen recipe, with the BSATR tending to have the most beneficial effects.
Animals ; Antigens, CD34 ; metabolism ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Embryo Implantation ; physiology ; Endometrium ; drug effects ; physiology ; ultrastructure ; Female ; Immunohistochemistry ; Mice ; Microscopy, Electron, Scanning ; Microvessels ; metabolism ; physiology ; Ovulation ; physiology ; Pregnancy ; Random Allocation ; Time Factors

OBJECTIVETo prepare a new targeted liposome ultrasonic contrast agent with anti-KDR antibody that binds specifically with KDR as the main receptor of VEGF and evaluate its physical characteristics, biological activity and specific binding capability in vitro.

METHODSA sonicator was used to prepare the biotinylated lipid micro-bubbles (MB-B), and biotin-avidin-mediated technique was used for attachment of anti-mouse KDR monoclonal antibody to the micro-bubble shell to generate MB-BAB-KDR. MB-BAB-KDR was incubated with fluorescent second antibody to assess the link condition, and the control groups were the MB-B and micro-bubbles with the antibody alone (MB-B-KDR). A parallel plate flow chamber system was used to characterize micro-bubbles attachment efficiency to KDR Fc.

RESULTSThe surface of the micro-bubbles could carry KDR antibody through the biotin-avidin bridge and MB-BAB-KDR were spherical and well-distributed. After incubation with the second antibody, MB-BAB-KDR could be observed to emit bright green fluorescence (Grade II) as compared with little or weak fluorescence in the control MB-B group (Grade 0) and MB-B-KDR group (Grade I). Targeted micro-bubbles bound to KDR Fc increased as the KDR Fc concentration increased (P<0.05).

CONCLUSIONThe targeted liposome contrast agent linked with KDR antibody by biotin-avidin bridge we prepared shows an increased binding number as the KDR Fc concentration increases, which provides a novel approach to molecular imaging study of endometrial receptivity.

Animals ; Antibodies, Monoclonal ; Contrast Media ; chemistry ; Endometrium ; physiology ; Female ; Liposomes ; chemistry ; Mice ; Microbubbles ; Molecular Imaging ; Sonication ; Ultrasonography ; Vascular Endothelial Growth Factor Receptor-2 ; immunology

Asoprisnil, a member of the selective progesterone receptor modulators, exerts high progesterone receptor selectivity, endometrial targeted advantages and significant anti-implantation effect in rats. The purpose of this study was to confirm the anti-implantation effect of asoprisil, investigate the ultrastructural changes of the peri-implantation endometrium in mice and explore the effect of asoprisnil on endometrial receptivity and its targeted contraceptive proficiency. Post-coitus mice were administered with different dosages (0.2, 0.1, 0.05 mg·g(-1)·day(-1)) of asoprisnil from day 1 of pregnancy to day 3. Then 3 animals in each group were killed on day 5 of pregnancy, and uteri were collected to examine the ultrastructural changes of endometria under a transmission electron microscope (TEM). A total of 80 animals were sacrificed on day 8 of pregnancy, and the uterine horns were examined for the presence or absence of nidation sites and the number of implantation embryos. The results showed that the implantation rate and the average number of implantation embryos in asoprisnil groups were statistically significantly decreased as compared with the vehicle control group (P<0.05). The TEM results revealed that, in vehicle control group, the tight junction between the luminal epithelia cells was short and straight, the gap was wide; the luminal epithelia cells were covered with plenty of short, clavate and neatly arranged microvilli; the endometril stromal cells were large with plenty of cytoplasm, and showed significant decidual change; there was more than one nucleus in stromal cells, and the karyotheca was integrity. In low dosage and high dosage asoprisnil groups, the tight junction was longer and more curve than in the vehicle control group; microvilli were uneven and asymmetrically distributed in luminal epithelia; the stromal cells were small and the decidual change was not significant; there were karyopyknosis and karyolysis in stromal cells; there were abnormal thick-wall vessels in the endometrium. It was suggested that asoprisnil changed the ultrastructure of the endometrium in implantation window, disturbed the endometrial receptivity and finally resulted in embryo implantation failure.
Animals ; Contraception, Postcoital ; methods ; Embryo Implantation, Delayed ; drug effects ; physiology ; Endometrium ; drug effects ; physiology ; ultrastructure ; Estrenes ; administration & dosage ; Female ; Mice ; Oximes ; administration & dosage ; Oxytocics ; administration & dosage ; Pregnancy ; Pregnancy, Animal ; Treatment Outcome

OBJECTIVETo study the clinical effects of Yupei Qisun Sequential Method (YQSM, by Shen supplementing and Pi invigorating) of Chinese medicine on correlated indices of repeated implantation failure patients in the fresh cycle.

METHODSSixty patients with more than three failure cycles of in virto fertilization and embryo transfer (IVF-ET) or intracytoplasmic sperm injection (ICSI) were recruited. They were assigned to the treatment group (treated by IVF/ICSI and Chinese medicine) and the control group (treated by IVF/ICSI alone), 30 in each group. The total dose of gonadotropin (Gn), the days of controlled ovary hyperstimulation (COH), the thickness of endometrium on the day of embryo transplantation, the number of retrieved oocytes, the fertilization number, the embryo number, the high quality embryo number, the pregnancy rate, and the implantation rate were compared.

RESULTSIn the treatment group the numbers of embryo and high quality embryo were 7.5 +/- 4.9 and 5.1 +/- 3.2 respectively, which were both higher than those of the control group with significant difference (5.1 +/- 3.2, 3.2 +/- 1.8; P < 0.05). No significant difference existed in aspects of the total numbers of Gn, the days of COH, the thickness of endometrium on the day of embryo transplantation, the numbers of retrieved oocytes, the fertilization number, the pregnancy rate, and the implantation rate between the two groups (P > 0.05).

CONCLUSIONYQSM combined with COH could improve the quantity and the quality of embryos, which was promising to increase the accumulative pregnancy rate of RIF patients.

Adult ; Embryo Transfer ; Endometrium ; physiology ; Female ; Fertilization in Vitro ; Gonadotropins ; administration & dosage ; Humans ; Medicine, Chinese Traditional ; methods ; Oocyte Retrieval ; Ovulation Induction ; Pregnancy ; Pregnancy Rate ; Sperm Injections, Intracytoplasmic ; Treatment Failure