The effectiveness of in vitro fertilization and embryo transfer remains limited in infertile women with moderate to severe intrauterine adhesions (IUA). Intrauterine infusion of autologous platelet-rich plasma (PRP) before embryo transfer has been reported to increase the endometrium thickness and clinical pregnancy rate in women with thin endometrium undergoing frozen-thawed embryo transfer (FET) cycles. This retrospective cohort study aims to investigate whether intrauterine autologous PRP infusion improves pregnancy outcomes of patients with moderate to severe IUA undergoing FET cycles. All consecutive FET cycles from November 2021 to December 2024 were screened for those in which moderate to severe IUA patients were treated with intrauterine autologous PRP infusion during endometrial preparation. Propensity score matching based on age and serum anti-Müllerian hormone levels was performed to select control patients without PRP infusion. The primary outcome was live birth. Multivariate logistic regression analysis was performed to adjust for confounding bias. A total of 180 cycles were included in this study, with 90 cycles in the PRP group and 90 cycles in the control group. The rates of live birth (36.7

Ovarian aging is characterized by depletion of the follicular reserve. The extracellular matrix (ECM) provides the essential microenvironmental niche for follicles, and aged-related alterations in ECM composition may adversely affect follicular dynamics. However, the precise relationship between matrix components and ovarian aging remains unclear. In this study, we first observed a marked reduction in type III collagen (Col III) as a key alteration associated with ovarian aging. Furthermore, we discovered that as a biomaterial, recombinant humanized type III collagen (rhCol III) ameliorated ovarian function in 12-month-old natural aging rats, evidenced by restored estrous cycles, increased ovarian index, elevated levels of anti-Müllerian hormone (AMH) and estradiol (E2) and enhanced folliculogenesis. Notably, rhCol III promoted the reorganization of the disorganized ovarian ECM into a highly ordered and dense structure, providing a supportive biological scaffold for follicular development. Additionally, supplementation of rhCol III could mitigate oxidative stress and mitochondrial dysfunction in aged granulosa cells (GCs), thereby preventing apoptosis and cellular senescence. Mechanistically, rhCol III bound to the integrin α2 (ITGA2) receptor on GCs and activated the PI3K/Akt signaling pathway. Our findings highlight Col III deficiency as a critical factor in ovarian aging and demonstrate that rhCol III supplementation rejuvenates the ovarian microenvironment via the ITGA2-PI3K/Akt axis, presenting a novel therapeutic strategy. Thus ITGA2 may represent a promising target for mitigating ovarian aging.

BACKGROUND:Recurrent spontaneous abortion (RSA), the common early pregnancy complication, remains elusive in its pathogenesis and treatment. Recombinant humanized type III collagen (rhCOLIII), a novel biomaterial, has demonstrated efficacy in treating various diseases. However, the role of rhCOLIII in RSA is unclear. This study aimed to explore the therapeutic potential and underlying mechanisms of rhCOLIII in RSA at single-cell resolution. METHODS:Human endometrium/decidua samples derived from healthy donors/normal pregnant and RSA patients were obtained to detect type III collagen (COLIII) expression via immunohistochemistry (IHC) and Western blot. A murine RSA model (CBA/J ♀ × DBA/2 ♂) was established, followed by intrauterine perfusion of rhCOLIII to evaluate its therapeutic efficacy. Uterine tissues from RSA and rhCOLIII-treated mice were collected on gestation day 8 for single-cell RNA sequencing, with findings validated by IHC, multiplex IHC (mIHC), and flow cytometry (FCM). RESULTS:COLIII expression was significantly reduced in RSA endometrial/decidual tissues. Intrauterine rhCOLIII treatment in a murine RSA model significantly decreased the embryo resorption rate from 31.62% to 3.82% (P < 0.001). Single-cell analysis identified 19 cell clusters, with stromal cells as the predominant population, further classified into seven functional subtypes and their differential composition between the RSA and rhCOLIII groups was confirmed by mIHC. Furthermore, rhCOLIII reprogrammed stromal cell function by activating oxidative-stress response pathways and regulating decidualization. Concurrently, our results showed that rhCOLIII could enhance anti-inflammatory macrophage activity and increase CD16+ NK cell abundance. Cell-cell communication analysis uncovered that APOE-TREM2 signaling between decidual stromal cells and macrophages, as well as BSG-PPIA signaling in decidual stromal cell-NK cell interactions, was augmented following rhCOLIII treatment. FCM analysis demonstrated that rhCOLIII increased TREM2+ macrophages associated with M2 polarization. CONCLUSIONS:Our study demonstrates that rhCOLIII exerts therapeutic effects in RSA mice potentially by modulating stromal cell decidualization and promoting a protective immune microenvironment, highlighting a promising therapeutic strategy for RSA.

To conduct a comparative metabolomic analysis of follicular fluid (FF) from patients undergoing in vitro fertilization (IVF) cycles under GnRH agonist versus antagonist protocols, aiming to identify protocol-specific metabolic signatures and explore their associations with embryological outcomes, thereby elucidating the metabolic basis for outcome differences and identifying modifiable metabolic factors to expand the scope for improving IVF outcomes. This study included 94 patients (47 per group) propensity score-matched for age, body mass index (BMI), anti-Müllerian hormone (AMH), and antral follicle count (AFC). FF samples collected during oocyte retrieval were analyzed using gas chromatography-mass spectrometry (GC-MS). The concentrations of identified metabolites were compared between groups and correlated with key laboratory parameters including the number of retrieved oocytes, Day 3 high-quality embryos, blastocysts, and high-quality blastocysts, as well as cumulative clinical pregnancy rates. The patients in GnRH agonist group were found to have better ovarian response, reflected by increased numbers of retrieved oocytes. Metabolomic profiling identified 58 differentially abundant metabolites between the two protocols. The levels of three key fatty acids, 11,14,17-eicosatrienoic acid, homo-γ-linolenic acid, and pentadecanoic acid, markedly decreased in the antagonist group (fold change < 0.75, variable importance in projection > 1.5). These metabolites exhibited strong power to discriminate between the protocols (area under the curve > 80

BACKGROUND:The aetiology and pathogenesis of adenomyosis remain unclear. This study utilised untargeted metabolomics to explore the aberrant amino acid metabolism in adenomyosis. Among the studied metabolites, hydroxyproline is known to promote the proliferation and invasion of tumour cells. Due to detection limitations, hydroxyproline levels were inferred via the expression of prolyl 4-hydroxylase subunit alpha 1 (P4HA1), a crucial enzyme that catalyses the conversion of proline to hydroxyproline. METHODS:Endometrial metabolomic analysis was performed using gas chromatography-mass spectrometry (GC-MS) in 15 and 20 patients with and without adenomyosis. The expression levels of P4HA1 mRNA and protein were detected using quantitative PCR (qPCR), western blotting, and immunohistochemistry. In vitro, Cell Counting Kit-8, and 5-Ethynyl-2'-deoxyuridine (EdU) assays were used to investigate the effect of hydroxyproline on the proliferation of human endometrial stromal cells (hESCs). Additionally, a wound-healing assay was conducted to examine the effect of hydroxyproline on hESCs migration. RESULTS:In total, 22 differentially expressed metabolites were identified in the adenomyosis group compared to the control group. qPCR results demonstrated that P4HA1 mRNA expression levels were significantly higher in the adenomyosis group than in the control group (p < 0.01), which was further validated at the protein level by western blotting and immunohistochemistry. In vitro, functional assays revealed that hydroxyproline promoted hESCs proliferation and migration in a dose-dependent manner. EdU assays showed a significant increase in the number of EdU-positive hESCs in the 5 mM hydroxyproline treatment group than that in the control group (p < 0.01). Additionally, wound healing assays demonstrated enhanced migration of hESCs after treatment with 5 mM hydroxyproline (p = 0.002). CONCLUSION:Hydroxyproline levels were significantly elevated in the endometrial tissues of patients with adenomyosis. Furthermore, hydroxyproline promotes the proliferation and migration of hESCs. These findings provide new insights into the pathogenesis of adenomyosis and suggest potential therapeutic strategies.

[This corrects the article DOI: 10.1016/j.mtbio.2024.101220.].

The differentiation of endometrial stromal cells (ESCs) into decidual stromal cells (DSCs), that is, endometrial decidualization, orchestrates the receptive environment for early embryo development, and defects in decidualization lead to unexplained recurrent spontaneous abortion (URSA). Nuclear receptor subfamily 5 group A member 1 (NR5A1) is involved in endometrial decidualization during early pregnancy, but its role is limitedly understood. Here, we elucidated the association between low expression of NR5A1 and decidualization dysregulation and URSA during early pregnancy, and then elucidated mechanisms of NR5A1 regulating decidualization. In the endometrium, the expression level of NR5A1 in secretory-phase ESCs of URSA patients was lower than that of controls. During early pregnancy, the expression level of NR5A1 in DSCs from URSA patients, and that in decidua of recurrent spontaneous abortion (RSA) mice, were decreased in comparison with controls, respectively. NR5A1 knockdown impaired in vitro decidualization of ESCs by inhibiting the IGFBP1 up-regulation and F-actin formation. In DSCs of early pregnancy mice, NR5A1 was maintained at a higher level from pregnant Day 4. Downknocking NR5A1 by intrauterine injection of RNAi-Nr5a1 lentiviruses in mice increased the embryonic resorption and impaired decidualization by down-regulating the expression of Dtprp and IGFBP1. Dual-luciferase reporter and ChIP-qPCR assays revealed that NR5A1 bound to the IGFBP1 promoter and then activated its transcription. In mice with downknocked NR5A1 in the uterus, restoring IGFBP1 expression by injecting Igfbp1-overexpression lentiviruses rescued embryonic resorption. These data indicated that NR5A1 was indispensable for endometrial decidualization and that the NR5A1 reduction in secretory endometrium and early decidua may lead to URSA.

Ovarian cancer (OC) is one of the leading causes of death from malignancy in women and lacks safe and efficient treatment. The novel biomaterial, recombinant humanized collagen type III (rhCOLIII), has been reported to have various biological functions, but its role in OC is unclear. This study aimed to reveal the function and mechanism of action of rhCOLIII in OC. We developed an injectable recombinant human collagen (rhCOL)-derived material with a molecular weight of 45kDa, with a stable triple helix structure, high biocompatibility, water solubility and biosafety. The anti-tumor activity of rhCOLIII was comprehensively evaluated through in vitro and in vivo experiments. In vitro, our results showed that rhCOLIII inhibited the proliferation, migration, and invasion of ovarian cancer cells (OCCs), and induced apoptosis. In addition, rhCOLIII not only inhibited autophagy of OCCs but also increased the expression of MHC-1 molecule within OCCs. To further elucidate the mechanism of rhCOLIII in OC, we conducted joint analysis of RNA-Seq and proteomics, and found that rhCOLIII exerted anti-tumor function and autophagy inhibition by downregulating Glutathione S-transferase P1 (GSTP1). Furthermore, various rescue experiments were designed to demonstrate that rhCOLIII suppressed autophagy and proliferation of OCCs by mediating GSTP1. In vivo, we found that rhCOLIII could inhibit tumor growth and promote CD8+ T cell infiltration. Our results indicate that rhCOLIII has great anti-tumor potential activity in OC, and induces protective anti-tumor immunity by regulating autophagy through GSTP1. These findings illustrate the potential therapeutic prospects of rhCOLIII for OC treatment.

In brief The mechanism underlying the accumulation of γδT cells in the decidua, which helps maintain maternal–fetal immunotolerance in early pregnancy, is unknown. This study reveals that DSC-derived RANKL upregulates ICAM-1 expression via the NF- κ B pathway to enable γδT cell accumulation in the early decidua. Abstract Decidual γδT (dγδT) cells help maintain maternal–fetal immunotolerance in early pregnancy. However, the mechanism underlying the accumulation of γδT cells in the decidua is unknown. Previous work showed that RANKL upregulated intercellular adhesion molecule 1 (ICAM-1) in decidual stromal cells (DSCs), and Rankl knockout mice had limited dγδT cell populations. In this study, we measured the expression levels of RANKL/RANK and ICAM-1 in DSCs, in addition to the integrins of ICAM-1 on dγδT cells, and the number of dγδT cells from patients with recurrent spontaneous abortion (RSA) and normal pregnant women in the first trimester. RSA patients showed significantly decreased RANKL/RANK and ICAM-1/CD11a signaling in decidua, and a decreased percentage of dγδT cells, which was positively correlated with DSC-derived RANKL and ICAM-1. Next, an in vitro adhesion experiment showed that the enhanced attraction of human DSCs to dγδT cells after RANKL overexpression was almost completely aborted by anti-ICAM-1. Furthermore, Rankl knockout mice showed a significant reduction in NF- κ B activity compared with wild-type controls. Finally, we applied a selective NF- κ B inhibitor named PDTC to validate the role of NF- κ B in RANKL-mediated ICAM-1 upregulation. Taken together, our data show that DSC-derived RANKL upregulates ICAM-1 expression via the NF- κ B pathway to enable γδT cell accumulation in the early decidua. A reduction in RANKL/ICAM-1 signaling in DSCs may result in insufficient accumulation of γδT cells in decidua and, in turn, RSA.

Disruption of the extracellular matrix and dysregulation of the balance between Th17 and regulatory T cells are recognized as risk factors for recurrent spontaneous abortion (RSA). However, the interaction between matrix components and the Th17/Treg axis remains poorly elucidated. The result of this study revealed that the absence of type I collagen in the decidua is linked to Th17/Treg imbalance in RSA. Furthermore, we discovered that biomaterial recombinant humanized type I collagen (rhCOLI) promoted T cell differentiation into Tregs by inhibition the Notch1/Hes1 signaling pathway and enhanced the immunosuppressive function of Tregs, as indicated by increased secretion level of IL-10 and TGF-β. Importantly, this study is the first to demonstrate that rhCOLI can modulate the Th17/Treg imbalance, reduce embryo resorption rates, reshape the immune microenvironment at the maternal-fetal interface, and improve fertility in an RSA mouse model. Collectively, these findings suggest that type I collagen deficiency may contribute to, rather than result from, RSA, and propose a potential intervention for RSA using rhCOLI.

Abstract Purpose To summarize the findings of relevant randomized controlled trials (RCTs) and conduct a meta-analysis to investigate the potential effect of aromatase inhibitors on preventing moderate to severe ovarian hyperstimulation syndrome (OHSS) in infertile women undergoing in vitro fertilization (IVF). Methods We searched for relevant RCTs in electronic databases, including MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov (from inception to August 2023). In addition, we manually searched the related reviews and reference lists of included studies for further relevant studies. We included RCTs where aromatase inhibitors prescribed either during controlled ovarian stimulation (COS) or in early luteal phase. The meta-analysis was performed using RevMan 5.4.1 software. The primary outcome was the incidence of moderate to severe OHSS. A descriptive analysis was conducted in cases where a meta-analysis was not feasible due to heterogeneity or lack of comparable data. Results 2858 records were retrieved and 12 RCTs were finally included. Letrozole was administered in the treatment group during COS in seven RCTs, whereas in the early luteal phase in five RCTs. Compared with the control group, the risk of moderate to severe OHSS significantly reduced by 55% in the letrozole group (RR 0.45, 95% CI 0.32 to 0.64, I 2 = 0%, 5 RCTs, 494 patients). Moreover, serum estradiol (E2) levels on hCG trigger day significantly decreased with the administration of letrozole during COS (MD -847.23, 95% CI -1398.00 to -296.47, I 2 = 93%, 5 RCTs, 374 patients). And serum E2 levels on the 4th, 5th and 7th to 10th day after hCG trigger were also significantly lower than those in the control group when letrozole was administered in the early luteal phase. Conclusions Patients with high risk of OHSS probably benefit from letrozole, which has been revealed to reduce the incidence of moderate to severe OHSS by this systematic review. However, the very limited number of participants and the quality of the included studies does not allow to recommend letrozole for the prevention of severe OHSS.

目的 系统评价血清抗苗勒管激素(AMH)水平对多囊卵巢综合征(PCOS)的诊断效能.方法 检索Embase和MEDLINE数据库,检索时限为建库至2021年11月17日,并手工检索相关文献的参考文献,纳入所有采用全自动化学发光免疫分析仪检测血清AMH水平的PCOS诊断性研究.按照纳入标准筛选文献,提取数据,采用诊断准确性研究的质量评估-2工具进行质量评价,应用Meta-Disc 1.4与Stata 17.0软件进行Meta分析.选用随机效应模型合并诊断效应量,并绘制综合受试者工作特征曲线.结果 该系统评价纳入10篇文献,共计6 437例研究对象.Meta分析结果显示,血清AMH水平诊断PCOS的合并灵敏度为0.81,合并特异度为0.91,合并诊断比值比为14.77,曲线下面积为0.88.结论 血清AMH水平对PCOS具有良好的诊断效能.

Abstract Recently, evidence has suggested that chronic endometritis (CE) is a crucial factor associated with infertility and failure of assisted reproductive techniques, prompting concern in the reproductive field. Studies have shown that persistent infiltered immune cells stimulation result in the disturbance of endometrial immune microenvironment could lead to the infertility of CE patients finally. Conventional treatments are limited because they lack immune regulation, so it is urgent to develop a novel approach to treat CE and promote embryo implantation in patients with CE. Herein, we prepared recombinant humanized type III collagen (rhCol III) with high cell adhesion activity to regulate macrophages and repair the endometrium. In this study, M1 macrophages and M1 macrophages cultured medium and lipopolysaccharide (LPS) co-stimulated inflammatory endometrium stromal cells (ESCs) were established in vitro to mimic CE condition. rhCol III promoted M1 macrophages toward M2 phenotype, improved cell migration, viability and collagen components of inflammatory ESCs. Also, the inflammatory response of inflammatory ESCs was downregulated after rhCol III treatment. Subsequently, LPS was used for CE rat model and a 28-day observation was performed; inflammatory cells’ infiltration, endometrium repair, extracellular matrix (ECM) remodeling and pregnancy outcomes were promoted after rhCol III endometrial infusion. In conclusion, rhCol III promoted (i) macrophage polarization toward M2 macrophages, (ii) pro-inflammatory cytokine production and anti-inflammatory cytokine reduction, (iii) ECM remodeling and (iv) fertility restoration. Meanwhile, rhCol III enhanced cell biological functions by interacting with discoidin domain receptors, regulated cell metabolism and reduced the inflammatory response through the inhibition of the NF-κB/YAP signaling pathway. Overall, the results illustrated the potential therapeutic prospects of rhCol III for CE treatment.

多囊卵巢综合征(PCOS)是女性常见的生殖内分泌代谢性疾病.部分PCOS患者因不孕需行体外受精-胚胎移植(IVF-ET)助孕.文献报道,PCOS患者在IVF助孕后发生卵巢过度刺激综合征、流产、极早产、妊娠期糖尿病和妊娠期高血压疾病的风险显著增加.在IVF助孕前给予药物预处理可能是改善PCOS患者妊娠结局的有效手段.本文对相关研究进行综述后发现,采用口服避孕药、二甲双胍、肌醇、生长激素或维生素D预处理,或在控制性促排卵期间应用前述药物,能改善PCOS患者的IVF结局.

Abstract Abnormal endometrial decidualization is closely related to embryo implantation failure and other pregnancy complications. Steroidogenic factor-1 (SF-1), which is also known as nuclear receptor subfamily 5 group A member 1, is a transcriptional activator that is involved in sexual differentiation and formation of the primary steroidogenic tissues. Its regulatory role in mouse and human endometrial decidualization remains unclear. In normal pregnant mice models, the expression of SF-1 was detected by immunohistochemistry and Western blot analysis. In normal pregnant mice, the expression of SF-1 at the implantation site is higher than that in the inter-implantation site. In the artificial decidualization in vivo and in vitro models, the expression of SF-1 increased with the deepening of decidualization. The high expression of SF-1 could promote the decidualization of endometrial stromal cells (ESCs). Based on the detection results of bisulfite sequencing PCR (BSP), the methylation of the CpG island in the SF-1 promoter region decreased after the decidualization of mouse endometrium. The interference of DNA methyltransferase (DNMT) expression promoted the expression of SF-1. The methylation inhibitor 5-aza resulted in the decrease in DNMTs, increase in SF-1 expression, and decidualization of ESCs. With the decidualization of the endometrium, the expression of SF-1 increased, whereas the DNA methylation of the SF-1 promoter decreased. The decrease in DNMTs resulted in increased SF-1 expression and promoted the decidualization of the endometrium. This study provides clues for the diagnosis and treatment of embryo implantation failure associated with abnormal decidualization.

Female reproductive disorders, such as premature ovarian insufficiency (POI), intrauterine adhesion (IUA) or thin endometrium, and polycystic ovary syndrome (PCOS), are the main factors affecting fertility. Mesenchymal stem cells derived–extracellular vesicles (MSC-EVs) have gained traction as a new potential treatment and were widely studied in these diseases. However, their impact is still not fully clear. A systematic search of PubMed, Web of Science, EMBASE, the Chinese National Knowledge of Infrastructure, and WanFang online databases was performed up to September 27th, 2022, and the studies of MSC-EVs-based therapy on the animal models of female reproductive diseases were included. The primary outcomes were anti-Müllerian hormone (AMH) in POI and endometrial thickness in IUA, respectively. 28 studies (POI, N = 15; IUA, N = 13) were included. For POI, MSC-EVs improved AMH at 2 weeks (SMD 3.40, 95

Increasing evidence supports that the co-treatment with growth hormone (GH) enhances ovarian response and oocyte quality during controlled ovarian stimulation (COS) in patients with diminished ovarian reserve (DOR). The composition of follicular fluid (FF) plays an essential role in oocyte development and mirrors the communication occurring between the oocyte and follicular microenvironment. However, the effect of GH on the FF metabolome remains unclear. This prospective observational study recruited DOR patients undergoing in vitro fertilization (IVF) cycles with minimal stimulation protocol for COS. Each patient receiving GH co-treatment was matched to a patient without GH co-treatment by propensity score matching. The FF was collected after isolating oocytes and assayed by gas chromatograph-mass spectrometry (GC-MS) metabolomics. The Pearson correlation was performed to evaluate the relationship between the number of oocytes retrieved and the levels of differential metabolites. The KEGG database was used to map differential metabolites onto various metabolic pathways. One hundred thirty-four FF metabolites were identified by GC-MS metabolomics. Twenty-four metabolites, including glutathione, itaconic acid and S-adenosylmethionin (SAM) showed significant differences between the GH and control groups (p-value < 0.05 and q-value < 0.1). In addition, the number of oocytes retrieved was significantly higher in the GH group compared to the control group (3 vs 2, p = 0.04) and correlated with the levels of five differential metabolites. Among them, the levels of antioxidant metabolite itaconic acid were upregulated by GH administration, while SAM levels were downregulated. The co-treatment with GH during COS may improve oocyte development by altering FF metabolite profiles in DOR patients. However, given the downregulation of SAM, a regulator of genomic imprinting, the potential risk of imprinting disturbances should not be neglected.

Maternal immunotolerance towards the semi-allogeneic foetus is critical for normal pregnancy (NP). As a secretory protein, growth arrest-specific factor 6 (GAS6) promotes cancer progression by inducing the conversion of tumour-associated macrophages to an immunosuppressive M2-like phenotype. However, little is known about whether GAS6 regulates decidual macrophages (dMφs) in the early maternal-foetal interface. In this study, first-trimester decidual tissues were obtained from normal pregnant women undergoing elective terminations and patients with miscarriages. The expression of GAS6 and its receptors (AXL, TYRO3 and MERTK) in decidua and GAS6 secretion by decidual stromal cells (DSCs) was measured. Then, we investigated the effect of recombinant human GAS6 (rhGAS6) on dMφs isolated from NP and THP-1 cells, and revealed the underlying mechanism. Both the expression of GAS6 in DSCs and MERTK in dMφs, in addition to GAS6 secretion by DSCs, was found to be significantly decreased in miscarriage patients compared to that in NPs. Additionally, we observed that rhGAS6 polarized dMφs and THP-1 cells towards an M2-like phenotype, as evidenced by the up-regulated CD163 expression. Moreover, rhGAS6 enhanced the clearance of toxic cell-free haemoglobin by dMφs by up-regulating CD163 expression, and rhGAS6 also boosted cell proliferation of dMφs and THP-1 cells. Finally, we demonstrated that rhGAS6 stimulated CD163 expression and cell proliferation by activating the PI3K/Akt signalling pathway. Collectively, these findings suggest that GAS6-mediated dialogue between DSCs and dMφs is crucial for the establishment and maintenance of maternal-foetal immunotolerance, and decreased GAS6 secretion by DSCs may lead to the occurrence of miscarriage in the first trimester.

生长停滞特异性蛋白6(growth arrest specific protein 6,GAS6)在肿瘤发生发展中发挥重要作用,其信号转导参与细胞增殖、黏附与迁移,但它在子宫内膜异位症(endometriosis,EMs)的相关功能及分子机制尚不明确.本研究从GEO数据库检索并下载子宫内膜异位症相关转录物组数据集,并对其进行GEO在线分析,筛选差异表达基因并进行GO聚类和KEGG通路富集分析.利用10例无内异症且无明确疾病妇女的在位子宫内膜,以及11例卵巢巧克力囊肿病人异位子宫内膜,对3个以上数据集共有的差异基因的mRNA水平进行实时荧光定量PCR验证.在子宫内膜异位症临床样本中,采用免疫组化、实时荧光定量PCR验证关键调控因子GAS6及上皮间充质转化(epi-thelial mesenchymal transition,EMT)标记基因的表达水平,并利用免疫荧光对GAS6和E-钙黏着蛋白(E-cadherin)进行共标.研究发现:从4个转录物组数据集中共筛选出47个差异表达基因,其主要富集于细胞迁移等过程以及MAPK、PI3K-AKT、紧密连接等相关信号通路.3个以上数据集所共有的9个差异基因在子宫内膜异位症病人中的mRNA水平均符合生物信息学分析的结果.GAS6在子宫内膜异位症病人异位内膜中的表达水平高于对照组(P＜0.05),并且子宫内膜异位症病人的内膜组织中存在EMT现象,EMT的标志物E-钙黏着蛋白表达水平下调(P＜0.05)、波形蛋白(vimentin)表达水平上调(P＜0.01).在GAS6高表达的子宫内膜异位症患者异位子宫内膜腺上皮细胞中,E-cadherin显示低表达,提示GAS6可能在子宫内膜异位症中介导EMT过程.综上所述,本研究初步揭示GAS6在子宫内膜异位症病人中高表达,及其可能介导EMT过程参与子宫内膜异位症的发生与发展,为子宫内膜异位症的临床治疗提供潜在靶标.

生殖道支原体是性传播疾病常见病原体之一,其中解脲支原体(Ureaplasma urealyticum,UU)、人型支原体(Mycoplasma hominis,Mh)和生殖支原体(Mycoplasma genitalium,Mg)与泌尿生殖道感染密切相关,其感染后附着于泌尿生殖道黏膜,损伤表层细胞,诱发炎症及免疫反应,被认为与非淋菌性尿道炎、宫颈炎、子宫内膜炎、不孕症等男女性生殖健康具有相关性,同时其可能导致流产、早产、胎膜早破、低出生体重儿等不良妊娠结局,但目前国内外文献对上诉问题尚无确切定论,故现将生殖道支原体感染与不孕及不良妊娠结局关系作一综述.