RESUMO
Obtaining high-quality embryos is one of the key factors to improve the clinical pregnancy rate of assisted reproductive technologies (ART). So far, the clinical evaluation of embryo quality depends on embryo morphology. However, the clinical pregnancy rate is still low. Therefore, new indicators are needed to further improve the evaluation of embryo quality. Several studies have shown that the decrease of sperm-specific protein actin-like 7A (ACTL7A) leaded to low fertilization rate, poor embryo development, and even infertility. The aim of this study was to study whether the different expression levels of ACTL7A on sperm can be used as a biomarker for predicting embryo quality. In this study, excluding the factors of severe female infertility, a total of 281 sperm samples were collected to compare the ACTL7A expression levels of sperms with high and low effective embryo rates and analyze the correlation between protein levels and in-vitro fertilization (IVF) laboratory outcomes. Our results indicated that the ACTL7A levels were significantly reduced in sperm samples presenting poor embryo quality. Furthermore, the protein levels showed a significant correlation with fertilization outcomes of ART. ACTL7A has the potential to be a biomarker for predicting success rate of fertilization and effective embryo and the possibility of embryo arrest. In conclusion, sperm-specific protein ACTL7A has a strong correlation with IVF laboratory outcomes and plays important roles in fertilization and embryo development.
Assuntos
Fertilização in vitro , Técnicas de Reprodução Assistida , Biomarcadores/metabolismo , Feminino , Fertilização , Humanos , Masculino , Gravidez , Taxa de Gravidez , Espermatozoides/metabolismoRESUMO
Androgen insensitivity syndrome (AIS) is an X-linked recessive genetic disease characterized by disorders of sex development, commonly caused by mutations of the androgen receptor (AR) gene. Herein, we identified a novel hemizygous mutation (c.2118T > A, p. Asn706Lys) of AR resulting in complete androgen insensitivity syndrome (CAIS) in twins. This missense mutation contributed to significantly decreased mRNA transcription and protein expression. In addition, structure model analysis showed that Asn706Lys resulted in loss of hydrogen bond with Asp891 and reduced protein stability. Furthermore, the mutant AR failed to bind to ligand due to the loss of hydrogen bond with dihydrotestosterone (DHT). This disrupted the translocation of AR protein from cytoplasm to nucleus after hormone stimulation. Our findings firstly demonstrated the novel mutation of c.2118T > A in AR directly caused CAIS. This contributed to expanding the AR mutational spectrum and revealed the pathogenic mechanism of AIS, as well as facilitating precise diagnosis and genetic counseling.
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Síndrome de Resistência a Andrógenos , Síndrome de Resistência a Andrógenos/diagnóstico , Síndrome de Resistência a Andrógenos/genética , Di-Hidrotestosterona , Humanos , Masculino , Mutação , Mutação de Sentido Incorreto , Receptores Androgênicos/genéticaRESUMO
Intervertebral disc degeneration (IDD) leads to low back pain (LBP). This study aimed to determine the regulation of IDD by competing endogenous RNAs (ceRNAs). We obtained the GSE63492, GSE124272, and GSE129789 datasets from the Gene Expression Omnibus database. The changes of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in IDD were characterized. The significantly changed mRNAs were subjected to protein-protein interaction analysis using the STRING database, and its functions and involved pathways were analyzed using the DAVID database and gene set enrichment analysis (GSEA). The significant changed lncRNAs, miRNAs and mRNAs were linked in a ceRNA network based on their interactions - predicted by Starbase and miRWalk. Differentially methylated loci of significantly changed mRNAs in early and advanced IDD were compared using the GSE129789 dataset. We identified 245 significantly changed mRNAs, 133 lncRNAs, and 228 miRNAs between patients with IDD and normal individuals. GSEA suggested that 17 pathways related to cell proliferation were activated while 35 cell signaling and immune-related pathways were suppressed in IDD. The following ceRNA network in IDD was built: LINC00665/hsa-miR-7-5p/FZD3, ZNF549; LINC00665/hsa-let-7e-5p/FZD3, ACVR2B; TRG-AS1/hsa-miR-574-5p/ACVR2B, P3H2; TRG-AS1/ hsa-let-7e-5p/FZD3, ACVR2B; and ZNF571-AS1/let-7e-5p/ACVR2B, FZD3. A lncRNA-miRNAmRNA ceRNA network which might regulate the progression of IDD was developed.
Assuntos
Degeneração do Disco Intervertebral , MicroRNAs , RNA Longo não Codificante , Biologia Computacional , Redes Reguladoras de Genes , Humanos , Degeneração do Disco Intervertebral/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genéticaRESUMO
Neuropathic pain (NP) is a chronic pain directly caused by injury or disease of the somatosensory nervous system. Previous studies suggest that GTP cyclohydrolase I (GCH1) may play a pivotal role in microglial activation, which has been shown to be essential for NP. However, its underlying mechanisms in microglial activation remain unclear. A wide range of microRNAs (miRNAs) have been found to be involved in microglial activation-induced NP. To identify the miRNAs regulated by GCH1 and predict their functions in the progression of microglial activation, we analyzed the miRNA expression profiles of GCH1-knockdown (KD) BV2 microglial cells. Small RNA-sequencing analysis revealed 13 differentially expressed (DE) miRNAs in GCH1-KD cells. The target genes of DE miRNAs mainly participate in PI3K-Akt signaling pathway, peroxisome and ferroptosis. The miRNA-mRNA regulatory network analysis showed that GCH1, MAP4K5 and YWHAB acted as hub genes. qRT-PCR results further verified the expression levels of mmu-miR-1a-3p, mmu-miR-133a-3p, mmu-miR-7a-5p and mmu-miR-10a-5p in GCH1-KD cells, which were consistent with the sequencing data. In addition, our data indicated that overexpression of mmu-miR-133a-3p alleviated the pro-inflammatory cytokines IL-1ß and IL-6 production induced by lipopolysaccharide (LPS), indicating that mmu-miR-133a-3p has a negative effect on microglial activation. Taken together, our findings suggest that many miRNAs regulated by GCH1 may be involved in microglial activation, which may provide new potential targets for GCH1 in the pathogenesis of NP.
Assuntos
GTP Cicloidrolase/metabolismo , MicroRNAs/metabolismo , Microglia/enzimologia , Neuralgia/enzimologia , Transcriptoma , Proteínas 14-3-3/genética , Proteínas 14-3-3/metabolismo , Animais , Linhagem Celular , GTP Cicloidrolase/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , MicroRNAs/genética , Microglia/efeitos dos fármacos , Neuralgia/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismoRESUMO
OBJECTIVE: This was a prospective study to investigate whether progesterone affects sperm activity by regulating the cyclic AMP-protein kinase A (cAMP-PKA) signalling pathway via α/ß hydrolase domain-containing protein 2 (ABHD2). METHODS: Spermatozoa were collected from healthy and infertile men (with oligoasthenospermia or abnormal acrosome; n = 30/group). The expression of and mutations in ABHD2 were detected by quantitative PCR, western blot, and gene sequencing. The expression of ABHD2 in the presence of progesterone was detected in all groups, and cAMP and PKA levels were detected by ELISA in fertile men after treatment with ABHD2 antibody and PKA inhibitor H-89, respectively. RESULTS: Expression of ABHD2 mRNA and protein were reduced in spermatozoa from infertile compared with fertile men. Four gene mutation sites were detected in spermatozoa from the infertile groups. Progesterone increased mRNA and protein levels of ABHD2 in healthy spermatozoa but not in spermatozoa from infertile men. The levels of cAMP and PKA were increased by progesterone in healthy spermatozoa, and the progesterone-increased cAMP and PKA were decreased by ABHD2 antibody and H-89, respectively. CONCLUSION: Progesterone regulates the ABHD2-mediated cAMP-PKA signalling pathway in healthy spermatozoa, which provides a new target for clinical diagnosis and treatment of infertility.
Assuntos
AMP Cíclico , Progesterona , Reação Acrossômica , Proteínas Quinases Dependentes de AMP Cíclico/genética , Humanos , Hidrolases , Masculino , Progesterona/farmacologia , Estudos Prospectivos , EspermatozoidesRESUMO
Several studies have confirmed that microglia are involved in neuropathic pain. Inhibition of guanosine-5'-triphosphate cyclohydrolase 1 (GTPCH1) can reduce the inflammation of microglia. However, the precise mechanism by which GTPCH1 regulates neuropathic pain remains unclear. In this study, BV2 microglia were transfected with adenovirus to knockdown GTPCH1 expression. High throughput sequencing analysis revealed that the mitogen-activated protein kinase (MAPK) related pathways and proteins were the most significantly down-regulated molecular function. Co-expression network analysis of Mapk14 mRNA and five long noncoding RNAs (lncRNAs) revealed their correlation. Quantitative reverse transcription-polymerase chain reaction revealed that among five lncRNAs, ENSMUST00000205634, ENSMUST00000218450 and ENSMUST00000156079 were related to the downregulation of Mapk14 mRNA expression. These provide some new potential targets for the involvement of GTPCH1 in neuropathic pain. This study is the first to note the differential expression of lncRNAs and mRNA in GTPCH1 knockdown BV2 microglia. Findings from this study reveal the mechanism by which GTPCH1 activates microglia and provide new potential targets for microglial activation in neuropathic pain.
RESUMO
Early embryonic arrest is a challenge for in vitro fertilization (IVF). No genetic factors were previously revealed in the sperm-derived arrest of embryonic development. Here, we reported two infertile brothers presenting normal in conventional semen analysis, but both couples had no embryos for transfer after several IVF and intracytoplasmic sperm injection (ICSI). Whole-exome sequencing identified a homozygous missense mutation of ACTL7A in both brothers. This mutation is deleterious and causes sperm acrosomal ultrastructural defects. The Actl7a knock-in mouse model was generated, and male mutated mice showed sperm acrosomal defects, which were completely consistent with the observations in patients. Furthermore, the sperm from ACTL7A/Actl7a-mutated men and mice showed reduced expression and abnormal localization of PLCζ as a potential cause of embryonic arrest and failure of fertilization. Artificial oocyte activation could successfully overcome the Actl7a-mutated sperm-derived infertility, which is meaningful in the future practice of IVF/ICSI for the ACTL7A-associated male infertility.
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Prohibitin (PHB), an evolutionarily conserved mitochondrial inner membrane protein, is highly expressed in cells that require strong mitochondrial function. Recently, we demonstrated that the deletion of Phb in spermatocytes results in impaired mitochondrial function. In addition, PHB expression in the mitochondrial sheath of human sperm has a significantly negative correlation with mitochondrial reactive oxygen species levels, but a positive one with mitochondrial membrane potential and sperm motility. These results suggest that mitochondrial PHB expression plays a role in sperm motility. However, the mechanism of PHB-mediated regulation of sperm motility remains unknown. Here, we demonstrate for the first time that PHB interacts with protein kinase B (AKT) and exists in a complex with phospho-PHB (pT258) and phospho-AKT in the mitochondrial sheath of murine sperm, as determined using colocalization and coimmunoprecipitation assays. After blocking AKT activity using wortmannin (a phosphatidylinositol 3-kinase [PI3K] inhibitor), murine sperm have significantly ( P < 0.05) decreased levels of phospho-PHB (pT258) and the total and progressive motility. Furthermore, significantly ( P < 0.05) lower levels of phospho-PI3K P85 subunit α+γ (pY199 and pY467) and phospho-AKT (pS473; pT308) are found in sperm from infertile asthenospermic and oligoasthenospermic men compared with normospermic subjects, which suggest a reduced activity of the PI3K/AKT pathway in these infertile subjects. Importantly, these sperm from infertile subjects also have a significantly ( P < 0.05) lower level of phospho-PHB (pT258). Collectively, our findings suggest that the interaction of PHB with AKT in the mitochondrial sheath is critical for sperm motility, where PHB phosphorylation (pT258) level and PI3K/AKT activity are key regulatory factors.
Assuntos
Mitocôndrias/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Repressoras/metabolismo , Motilidade dos Espermatozoides , Adulto , Animais , Western Blotting , Eletroforese em Gel de Poliacrilamida , Imunofluorescência , Humanos , Imunoprecipitação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/fisiologia , Proibitinas , Proteínas Repressoras/fisiologia , Espermatozoides/metabolismo , Espermatozoides/fisiologiaRESUMO
BACKGROUND: MicroRNAs (miRNAs) are a class of noncoding small RNAs that play important roles in many physiological processes by regulating gene expression. Previous studies have shown that the expression levels of total miRNAs increase during mouse embryonic development, and some miRNAs control the regulatory network in development progression. However, few studies have focused on the effects of miRNAs on early human embryonic development. The relationship between miRNAs and early human embryogenesis is still unknown. RESULTS: In this study, RNA-seq data collected from sperm samples from 102 patients with a normal sperm index but treated with assisted reproductive technology (ART) were analyzed for the relationships between differentially expressed small RNAs and the fertilization rate (FR), blastocyst rate and high-quality embryo rate (HQER). The sperm samples with high hsa-mir-191 expression had a higher FR, effective embryo rate (EER) and HQER. hsa-mir-191 was used as a single indicator to predict the HQER. The receiver operating characteristic (ROC) curve had an area under the ROC curve (AUC) of 0.686. We also found that hsa-mir-191 expression is correlated with an abnormal sperm rate (cor = 0.29, p < 0.01). We also evaluated the relationship between hsa-mir-34c and early human embryo development in these 102 sperm samples and obtained negative results. CONCLUSIONS: These findings suggest that high hsa-mir-191-5p expression in sperm is associated with early human embryonic quality and that hsa-mir-191-5p could be used as a potential marker to screen high-quality sperm to improve the success rates of in vitro fertilization (IVF).
Assuntos
Desenvolvimento Embrionário/genética , Perfilação da Expressão Gênica , MicroRNAs/genética , Espermatozoides/metabolismo , Transcriptoma , Animais , Biomarcadores , Fertilização in vitro , Regulação da Expressão Gênica no Desenvolvimento , Biblioteca Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Camundongos , Curva ROCRESUMO
Neuropathic pain is a severe and chronic neurological disease caused by injury or disease of the somatosensory system. Currently, there are no effective treatments for neuropathic pain. Neuroinflammation, characterized by activation of spinal glial cells and increased production of pro-inflammatory cytokines (for example, IL-1ß, TNF-α and IL-6), is a pathophysiological process closely related to neuropathic pain. The anti-inflammatory drug sulfasalazine (SFZ) is approved for inflammatory bowel disease and rheumatoid arthritis. Although the analgesic effect of SFZ has been reported in diabetic mice, its role in neuropathic pain caused by peripheral nerve injury has not been clarified. Here, we show that SFZ significantly alleviated mechanical hypersensitivity and attenuated neuroinflammatory response in neuropathic pain induced by chronic constriction injury (CCI) in rats. Additionally, SFZ inhibited the activation of astrocytes and abolished the CCI-induced increase of NF-κB in the spinal cord. Hence, our results show that SFZ is a potential treatment for neuropathic pain induced by peripheral nerve injury.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Hiperalgesia/tratamento farmacológico , NF-kappa B/antagonistas & inibidores , Neuralgia/tratamento farmacológico , Sulfassalazina/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Doença Crônica , Constrição , Hiperalgesia/metabolismo , Masculino , NF-kappa B/metabolismo , Neuralgia/metabolismo , Ratos , Ratos Sprague-Dawley , Sulfassalazina/farmacologiaRESUMO
BACKGROUND: Semen cryopreservation has been widely applied in assisted reproductive technologies and sperm bank, but it causes considerable impairments on sperm quality. It is necessary to find an evaluation indicator for determining the sperm-freezing tolerance. METHODS: The glycocalyx of good freezability ejaculates was compared with poor freezability ejaculates by lectin microarray. The significant different lectins were validated by flow cytometry (FACS). To analyze the relationship between the potential biomarker and the tolerance of sperm to cryopreservation, 60 samples with different recovery rates were collected and detected the lectin-binding intensity by FACS. The receiver operating characteristic (ROC) curve was analyzed to test the capability of the lectin as a potential biomarker for detecting the sperm freezablility. RESULTS: ABA and DSL were found to develop significant differences between them. Further validation showed that ABA was significantly negative correlated with the sperm recovery rates (r = - 0.618, P < 0.000) and could be a potential biomarker for predicting sperm freezability (AUC = 0.733 ± 0.067, 95% CI 0.601 - 0.865, P < 0.01). CONCLUSION: ABA could be a potential biomarker for predicting sperm freezability. It will help to reduce sperm-freezing recovery tests and improve the efficiency of cryopreservation in human sperm bank.
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OBJECTIVE: To evaluate the impact of assisted reproductive technology (ART) on the offspring of Chinese population. DESIGN: Retrospective, data-linkage cohort. SETTING: Not applicable. PATIENT(S): Live births resulting from ART or natural conception. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Birth defects coded according to ICD-10. RESULT(S): Births after ART were more likely to be female and multiple births, especially after intracytoplasmic sperm injection (ICSI). ART was associated with a significantly increased risk of birth defects, especially, among singleton births, a significantly increased risk in fresh-embryo cycles after in vitro fertilization (IVF) and frozen-embryo cycles after ICSI. Associations between ART and multiple defects, between ART and gastrointestinal malformation, genital organs malformation, and musculoskeletal malformation among singleton births, and between ART and cardiac septa malformation among multiple births were observed. CONCLUSION(S): This study suggests that ART increases the risk of birth defects. Subgroup analyses indicate higher risk for both fresh and frozen embryos, although nonsignificantly for frozen embryos after IVF and for fresh embryos were presented with low power. Larger sample size research is needed to clarify effects from fresh- or frozen-embryo cycles after IVF and ICSI.
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Anormalidades Congênitas/diagnóstico , Anormalidades Congênitas/epidemiologia , Armazenamento e Recuperação da Informação/tendências , Sistema de Registros , Técnicas de Reprodução Assistida/tendências , Adulto , China/epidemiologia , Estudos de Coortes , Anormalidades Congênitas/etiologia , Transferência Embrionária/efeitos adversos , Transferência Embrionária/tendências , Feminino , Humanos , Recém-Nascido , Nascido Vivo/epidemiologia , Masculino , Gravidez , Técnicas de Reprodução Assistida/efeitos adversos , Estudos Retrospectivos , Adulto JovemRESUMO
The role of AMP-activated protein kinase (AMPK) in the regulation of energy metabolism and the control of skeletal muscle regeneration post injury has been described previously. It remains unknown whether this metabolic sensor plays a role in the mechanism of axonal regeneration post injury. In this study, we used a sciatic nerve crushed mouse model to detect the expression of AMPK in sciatic nerve and spinal motor neurons at 1 week, 2 weeks and 3 weeks after injury by immunofluorescence staining. Electrophysiological and histopathological studies were used to confirm the nerve injury and regeneration. Our results showed that frequency of AMPK-positive spinal motor neurons was significantly higher on day 7 after sciatic nerve crush (SNC) and peaked on day 14. No expression of AMPK was detected in axons of the sciatic nerve before and after the injury. Taken together, our study suggested a possible role of AMPK in the mechanism of motor nerve regeneration after injury.
Assuntos
Proteínas Quinases Ativadas por AMP/genética , Potenciais de Ação/fisiologia , Axônios/enzimologia , Neurônios Motores/enzimologia , Regeneração Nervosa/fisiologia , Neuropatia Ciática/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Axônios/ultraestrutura , Modelos Animais de Doenças , Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios Motores/ultraestrutura , Compressão Nervosa , Nervo Isquiático/citologia , Nervo Isquiático/enzimologia , Nervo Isquiático/lesões , Neuropatia Ciática/enzimologia , Neuropatia Ciática/patologia , Medula Espinal/citologia , Medula Espinal/enzimologia , Fatores de TempoRESUMO
Tamoxifen is administered for estrogen receptor positive (ER+) breast cancers, but it can induce uterine endometrial cancer and non-alcoholic fatty liver disease (NAFLD). Importantly, ten years of tamoxifen treatment has greater protective effect against ER+ breast cancer than five years of such treatment. Tamoxifen was also approved by the FDA as a chemopreventive agent for those deemed at high risk for the development of breast cancer. The side effects are of substantial concern because of these extended methods of tamoxifen administration. In this study, we found that anordrin, marketed as an antifertility medicine in China, inhibited tamoxifen-induced endometrial epithelial cell mitosis and NAFLD in mouse uterus and liver as an anti-estrogenic and estrogenic agent, respectively. Additionally, compared with tamoxifen, anordiol, the active metabolite of anordrin, weakly bound to the ligand binding domain of ER-α. Anordrin did not regulate the classic estrogen nuclear pathway; thus, it did not affect the anti-tumor activity of tamoxifen in nude mice. Taken together, these data suggested that anordrin could eliminate the side effects of tamoxifen without affecting its anti-tumor activity.
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Antineoplásicos Hormonais/efeitos adversos , Anticoncepcionais Orais Sintéticos/administração & dosagem , Neoplasias do Endométrio/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Norandrostanos/administração & dosagem , Tamoxifeno/efeitos adversos , Animais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/farmacologia , Linhagem Celular Tumoral , Neoplasias do Endométrio/induzido quimicamente , Feminino , Xenoenxertos , Humanos , Camundongos Endogâmicos ICR , Camundongos Nus , Transplante de Neoplasias , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Tamoxifeno/administração & dosagem , Tamoxifeno/farmacologia , Resultado do TratamentoRESUMO
Prohibitin (PHB), a major mitochondrial membrane protein, has been shown earlier in our laboratoryto regulate sperm motility via an alteration in mitochondrial membrane potential (MMP) in infertile men with poor sperm quality. To test if PHB expression is associated with sperm mitochondrial superoxide (mROS) levels, here we examined sperm mROS levels, high MMP and lipid peroxidation in infertile men with poor sperm motility (asthenospermia, A) and/or low sperm concentrations (oligoasthenospermia, OA). The diaphorase-type activity of sperm mitochondrial complex I (MCI) and PHB expression were also determined. We demonstrate that mROS and lipid peroxidation levels are significantly higher in sperm from A and OA subjects than in normospermic subjects, whereas high MMP and PHB expression are significantly lower. A positive correlation between mROS and lipid peroxidation and a negative correlation of mROS with PHB expression, high MMP, and sperm motility were found in these subjects. The finding of similar diaphorase-type activity levels of sperm MCI in the three groups studied suggests that the catalytic subunits of MCI in the matrix arm may produce mROS on its own. There may be a dysfunction of electron transport at MCI associated with decreased expression of PHB in sperm with poor quality. We conclude that mROS level is increased and associated with decreased PHB expression, and it may regulate sperm motility via increases in low MMP and lipid peroxidation. This is the first report on the involvement of PHB in human sperm motility loss associated with increased generation of mROS at MCI.
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Complexo I de Transporte de Elétrons/metabolismo , Mitocôndrias/efeitos dos fármacos , Proteínas Repressoras/farmacologia , Espermatozoides/efeitos dos fármacos , Superóxidos/metabolismo , Adulto , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Proibitinas , Espécies Reativas de Oxigênio/metabolismo , Contagem de Espermatozoides/métodos , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismoRESUMO
BACKGROUND: Clinical ovulation induction induces blood estrogen (E2) in excess of physiological levels, which can hinder uterine receptivity. In contrast, progesterone produces the opposite clinical effect, suggesting that it might be capable of recovering the lost receptivity resulting from exposure to high estrogen levels. Integrins are the most widely used biological markers for monitoring uterine conditions. We studied progesterone-induced changes in integrin ß expression patterns as biomarkers for changes in uterine receptivity in response to increased estrogen levels. METHODS: Endometrial biopsy samples from patients were screened for their estrogen (E2) and progesterone (P4) content and expressing levels of integrin ß1 and ß3. Uterine receptivity was evaluated using human endometrial adenocarcinoma cells in an embryo attachment model. The respective and concatenated effects of embryo attachment and changes in the integrin ß1 and ß3 expression patterns on the adenocarcinoma cell plasma membranes in response to 100 nM concentrations of E2 and P4 were evaluated. RESULTS: Increased blood E2 concentrations were associated with significantly decreased the levels of integrin ß3 expression in uterine biopsy samples. In vitro experiments revealed that a 100 nM E2 concentration inhibited the distribution of integrin ß3 on the plasma membranes of human endometrial adenocarcinoma cells used in the embryo attachment model, and resulted in decreased rates of embryo attachment. In contrast, P4 enhanced the expression of integrin ß1 and promoted its distribution on the plasma membranes. Furthermore, P4 recovered the embryo attachment efficiency that was lost by exposure to 100 nM E2. CONCLUSIONS: Blood E2 and P4 levels and integrin ß3 and ß1 expression levels in uterine biopsy samples should be considered as biomarkers for evaluating uterine receptivity and determining the optimal time for embryo transfer. Trial registration Trial number: ChiCTR-TRC-13003777; Name of registry: Chinese Clinical Trial Registry; Date of registration: 4 September 2013; Date of enrollment of the first study participant: 15 October 2013.