Chronic endometritis incidence in infertile women with and without polycystic ovary syndrome: a propensity score matched study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is known to be associated with chronic low-grade inflammation and endometrial dysfunction. Chronic endometritis (CE) is a type of local inflammation that can contribute to endometrial dysfunction in infertile women. Some clinicians recommend screening for CE in women at high risk, such as those with endometrial polyps. However, it is still uncertain whether there is a relationship between PCOS and CE, as well as whether women with PCOS require enhanced screening for CE. This study was to assess the incidence of CE among infertile women with PCOS by hysteroscopy combined with histopathology CD138 immunohistochemical staining of endometrium. METHODS: A total of 205 patients in the PCOS group and 4021 patients in the non-PCOS group from July 2017 to August 2022 were included in this retrospective study. After nearest-neighbor 1:4 propensity score matching (PSM), 189 PCOS patients were matched with 697 non-PCOS patients. Basic information was recorded. The CE incidence was compared. The risk factors affecting CE incidence were also analyzed. RESULTS: No significantly higher CE incidence in infertile women with PCOS were found either in total analysis or after PSM (P = 0.969; P = 0.697; respectively). Similar results were discovered in the subgroup of Body Mass Index (BMI) (P = 0.301; P = 0.671; P = 0.427; respectively) as well as the four PCOS phenotypes (P = 0.157). Intriguingly, the incidence of CE increased as BMI increased in the PCOS group, even though no significant differences were found (P = 0.263). Multivariate logistic regression showed that age, infertility duration, infertility type, PCOS, and obesity were not the independent risk factors affecting CE incidence. CONCLUSION: The incidence of CE in PCOS patients did not significantly increase compared to non-PCOS patients. Similarly, no significant differences in the incidence of CE were observed among different PCOS phenotypes. The current evidence does not substantiate the need for widespread CE screening among PCOS women, potentially mitigating the undue financial and emotional strain associated with such screenings.

Reconstructing gene regulatory networks of biological function using differential equations of multilayer perceptrons.

BACKGROUND: Building biological networks with a certain function is a challenge in systems biology. For the functionality of small (less than ten nodes) biological networks, most methods are implemented by exhausting all possible network topological spaces. This exhaustive approach is difficult to scale to large-scale biological networks. And regulatory relationships are complex and often nonlinear or non-monotonic, which makes inference using linear models challenging. RESULTS: In this paper, we propose a multi-layer perceptron-based differential equation method, which operates by training a fully connected neural network (NN) to simulate the transcription rate of genes in traditional differential equations. We verify whether the regulatory network constructed by the NN method can continue to achieve the expected biological function by verifying the degree of overlap between the regulatory network discovered by NN and the regulatory network constructed by the Hill function. And we validate our approach by adapting to noise signals, regulator knockout, and constructing large-scale gene regulatory networks using link-knockout techniques. We apply a real dataset (the mesoderm inducer Xenopus Brachyury expression) to construct the core topology of the gene regulatory network and find that Xbra is only strongly expressed at moderate levels of activin signaling. CONCLUSION: We have demonstrated from the results that this method has the ability to identify the underlying network topology and functional mechanisms, and can also be applied to larger and more complex gene network topologies.

Clinical outcomes after single-versus double-embryo transfers in women with adenomyosis: a retrospective study.

BACKGROUND: Adenomyosis affects the outcomes of spontaneous fertility and assisted reproductive technology. The single blastocyst embryo transfer (SBT) policy is an effective strategy known to minimize the risk of multiple pregnancy for non-adenomyosis women. However, little is known about its applicability to women with adenomyosis. The purpose of this study is to compare pregnancy outcomes between SBT, double-blastocyst embryo transfer (DBT), single-cleavage-stage embryo transfer (SET) and double-cleavage-stage embryo transfer (DET) in the frozen-thawed embryo transfer cycles among adenomyosis patients. METHODS: This retrospective study was conducted in all frozen-thawed autologous embryo transfer cycles. 393 frozen-thawed embryo transfer cycles performed in adenomyosis patients were enrolled. The major clinical outcomes were implantation rate (IR), clinical pregnancy rate (CPR), miscarriage rate (MR), multiple pregnancy rate (MPR) and live birth rate (LBR). RESULTS: The SBT and DBT groups achieved higher IR (P < 0.001), CPR (P = 0.017), LBR (P = 0.040) and lower MR (P = 0.020) than the SET and DET groups. But the SBT and DBT groups achieved similar CPR and LBR. The SBT and SET groups achieved lower MPR (P < 0.001) than the DBT and DET groups. The average birth weight (BW) of SBT groups was higher than the DBT and DET groups (P = 0.016). When compared with SBT group, low-birth-weight infants were significantly higher with DBT and DET. CONCLUSIONS: When performing frozen-thawed embryo transfer cycles among adenomyosis patients, the SBT group has similar IR, CPR, MR, LBR but lower MPR compared to the DBT group. Therefore, SBT might be offered as standard practice.

Causal role of immune cells in major depressive disorder and bipolar disorder: Mendelian randomization (MR) study.

BACKGROUND: Major depressive disorder (MDD) and bipolar disorder (BD) are prevalent psychiatric conditions linked to inflammatory processes. However, it is unclear whether associations of immune cells with these disorders are likely to be causal. METHODS: We used two-sample Mendelian randomization (MR) approach to investigate the relationship between 731 immune cells and the risk of MDD and BD. Rigorous sensitivity analyses are conducted to assess the reliability, heterogeneity, and horizontal pleiotropy of the findings. RESULTS: Genetically-predicted CD27 on IgD+ CD38- unswitched memory B cell (inverse variance weighting (IVW): odds ratio (OR) [95 %]: 1.017 [1.007 to 1.027], p = 0.001), CD27 on IgD+ CD24+ B cell (IVW: OR [95 %]: 1.021 [1.011 to 1.031], p = 4.821E-05) and other 12 immune cells were associated with increased risk of MDD in MR, while HLA DR++ monocyte %leukocyte (IVW: OR [95 %]: 0.973 [0.948 to 0.998], p = 0.038), CD4 on Central Memory CD4+ T cell (IVW: OR [95 %]: 0.979 [0.963 to 0.995], p = 0.011) and other 13 immune cells were associated with decreased risk of MDD in MR. Additionally, CD33+ HLA DR+ Absolute Count (IVW: OR [95 %]: 1.022[1.007 to 1.036], p = 0.007), CD28+ CD45RA- CD8+ T cell %T cell (IVW: OR [95 %]: 1.024 [1.008 to 1.041], p = 0.004) and other 18 immune cells were associated with increased risk of BD in MR, while CD62L on CD62L+ myeloid Dendritic Cell (IVW: OR [95 %]: 0.926 [0.871 to 0.985], p = 0.014), IgD- CD27- B cell %lymphocyte (IVW: OR [95 %]: 0.918 [0.880 to 0.956], p = 4.654E-05) and other 13 immune cells were associated with decreased risk of BD in MR. CONCLUSIONS: This MR study provides robust evidence supporting a causal relationship between immune cells and the susceptibility to MDD and BD, offering valuable insights for future clinical investigations. Experimental studies are also required to further examine causality, mechanisms, and treatment potential for these immune cells for MDD and BD.

Chronic endometritis positively correlates with the aggravation of intrauterine adhesions but has limited effects on reproductive prognosis with antibiotic application.

OBJECTIVE: To assess the effect of chronic endometritis (CE) diagnosed by CD138 staining on the aggravation of intrauterine adhesions (IUAs), and the reproductive prognosis after transcervical resection of adhesions (TCRA). METHODS: Sixty-three patients with severe IUAs (group A) and 119 patients with moderate IUAs (group B) were included in this retrospective study. TCRA and endometrial biopsy with CD138 staining were performed. Participants in each group were classified into two subgroups: CE group and NCE group (without CE). Patients were treated with a course of oral antibiotics for 2 weeks after TCRA. Embryo transfer would be performed if patients had embryos after operations. RESULTS: Increased incidence of CE was found in group A (18/63, 28.57%) compared with group B (18/119, 15.13%) (P = 0.030). No significant differences were found in the comparisons of chemical pregnancy rate, early miscarriage rate, or full-term pregnancy rate between the CE group and NCE group (P > 0.05), in either the subgroup analysis of group A and group B, or the total analysis. CONCLUSION: CE has a positive correlation with the aggravation of IUAs. CE did not have a negative impact on the reproductive prognosis of patients with moderate or severe IUAs after TCRA followed by antibiotic administration.

How platelet-rich plasma (PRP) intra-uterine injection improve endometrial receptivity of intrauterine adhesions in women: A time-series-based self-controlled study.

Platelet-rich plasma (PRP) treatment proven to improve fertility outcomes in patients with a poor endometrial environment. However, the mechanism is not yet clear. In this study, we recruited 6 patients with infertility due to IUA and 6 normal control women. The subjects in the IUA group collected samples before and after PRP treatment. Endometrial receptivity was improved after PRP treatment. After PRP treatment, the endometrial NK cells, CD8 T cells and Th1 cells were significantly lower than those before treatment. Functional enrichment analysis suggested that the effects of changes in microbial composition played an important role in changes in the endometrial immune environment. Among them, the most significant difference was Bacillus. Our self-controlled cohort in this study can fully describe the detailed mechanism by which PRP treatment improves the endometrial environment.

mRNA, lncRNA and Circular RNA Expression Profiles in Granulosa Cells of Infertile Women with Ovarian Endometriosis.

To explore the expression profiles of mRNAs, long-noncoding RNAs (lncRNAs), circular RNAs (circRNAs) and construct the competitive endogenous RNA networks in granulosa cells (GCs) of infertile women with ovarian endometriosis. RNA sequencing was conducted for RNA expression profiling from GCs of five women with ovarian endometriosis and five with tubal factor infertility. The differential expression of mRNAs, lncRNAs and circRNAs was compared. Then, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA networks were constructed. Finally, the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to determine the role of the differential expression of mRNA. A total of 12,498 mRNAs, 724 lncRNAs and 2269 circRNAs were identified in ovarian endometriosis and controls. 37 mRNAs, 51 lncRNAs and 101 circRNAs were detected to be differentially expressed in women with ovarian endometriosis. Ten lncRNAs and 22 differentially expressed mRNAs were selected to build the lncRNA-miRNA-mRNA network, while 12 circRNAs and four differentially expressed mRNAs were selected to build the circRNA-miRNA-mRNA network. GO analysis suggested that the differentially expressed mRNAs were mainly involved in regulation of cell differentiation, cell cycle while KEGG pathway analysis showed that pathways involved in the MAPK signaling pathway and FoxO signaling pathway were enriched with differentially upregulated mRNAs. We generated mRNAs, lncRNAs and circRNAs expression profiles and identified differentially expressed RNAs of GCs in infertile women with ovarian endometriosis. These findings provide a basis for further understanding of the underlying etiology of endometriosis-related infertility.

Endometrial polyp is associated with a higher prevalence of chronic endometritis in infertile women.

OBJECTIVE: To assess the prevalence of chronic endometritis (CE) among infertile women with endometrial polyps (EP). METHODS: From June 2017 to October 2021, 583 patients in the polyp group (group A-group A1: single-polyp group, 322 patients; group A2: multiple-polyp group, 261 patients) and 4534 patients in the non-polyp group (group B) were included in this retrospective study. Hysteroscopic polypectomy was performed in group A. Endometrial biopsy and CD138 immunohistochemistry staining for specimens was carried out in all groups. RESULTS: Prevalence of CE was significantly higher in group A than in group B (45.28% vs. 27.94%, P < 0.001). A significantly higher prevalence of CE was found in group A1 and group A2 compared with group B (42.24% vs. 27.94%, P < 0.001; 49.04% vs. 27.94%, P < 0.001; respectively). No significant difference in the comparison of CE prevalence was found between group A1 and group A2. Similar results were achieved in the subgroup analysis among patients aged 40 years or older and patients younger than 40 years. CONCLUSION: EP, either single EP or multiple EP, positively correlates with CE. The prevalence of CE was similar between the single-polyp group and the multiple-polyp group.

Correlation between hysteroscopy findings in patients with hydrosalpinx and chronic endometritis.

OBJECTIVE: To evaluate the role of hydrosalpinx in susceptibility to chronic endometritis (CE). METHODS: This is a retrospective cohort study, which includes 624 patients with hydrosalpinx (group A) and 789 patients without hydrosalpinx (group B) undergoing laparoscopy and hysteroscopy simultaneously. Endometrial morphology was recorded under hysteroscopy. Endometrial biopsy was obtained after hysteroscopy, and immunohistochemical staining for syndecan-1 (CD138) was carried out. RESULTS: No significantly statistical differences were found between the two groups when comparing the incidence of endometrial hyperemia or endometrial micro-polyps under hysteroscopy (P > 0.05). Hydrosalpinx had a significant impact on the incidence of CE (P < 0.05) (plasma cell count: no plasma cells: odds ratio [OR] 0.71, 95% confidence interval [CI] 0.58-0.88, P = 0.002; ≥1/high-power field [HPF]: OR 1.40, 95% CI 1.14-1.74, P = 0.002; ≥3/HPF: OR 1.50, 95% CI 1.18-1.91, P = 0.001; ≥5/HPF: OR 1.62, 95% CI 1.27-2.21, P < 0.001). There were no significant differences in the comparison of plasma cell count between the unilateral hydrosalpinx group (274 patients) and the bilateral hydrosalpinx group (350 patients) (P > 0.05). CONCLUSION: The presence of hydrosalpinx increased the incidence of CE. Bilateral hydrosalpinx did not significantly increase the incidence of CE compared with unilateral hydrosalpinx.

Transcriptomic analysis shows that surgical treatment is likely to influence the endometrial receptivity of patients with stage III/IV endometriosis.

Background: Endometriosis negatively affects fertility, and it is a common disease in assisted reproductive practice. Surgical removal of endometriotic lesions is widely carried out to relieve symptoms and promote fertility. But it is not intensively investigated what changes in the secretory eutopic endometrium of patients with endometriosis after surgery. Methods: Eighteen patients with stage III/IV endometriosis were included in the study, and they were divided into the untreated group and the treated group (6 vs. 12). Basic clinical data were compared, and transcriptomic data of the secretory eutopic endometrium were analyzed with DESeq2, Cytoscape, ClueGO, CluePedia, and Gene Set Enrichment Analysis (GSEA). CIBERSORT was used to calculate the relative abundance of 22 immune cells in the samples. Results: We determined 346 differentially expressed genes (DEGs) using DESeq2. These DEGs were used to enrich seven Gene Ontology terms including three associated with immune processes and one correlated to prostaglandin using ClueGO and CluePedia. GSEA enriched 28 Gene Ontology terms in the treated group mainly associated with immune and blood pressure regulation process. Compared to the untreated group, the relative abundance of resting CD4+ memory T cells [0.218 (0.069, 0.334) vs. 0.332 (0.181, 0.429), P = 0.022] and the even less abundant memory B cells [0.001 (0.000, 0.083) vs. 0.033 (0.007, 0.057), P = 0.049] are significantly decreased in the treated group. Conclusion: Surgical treatment of stage III/IV endometriosis influences some genes and biological processes related to endometrial receptivity, but more evidence is needed.

Overexpression of long non-coding RNA nuclear enriched abundant transcript 1 inhibits the expression of p53 and improves premature ovarian failure.

It has been previously reported that the long non-coding RNA nuclear enriched abundant transcript 1 (NEAT1) can regulate cell apoptosis. The present study aimed to investigate the involvement of NEAT1 in premature ovarian failure (POF). A total of 60 patients with POF admitted at the Sixth Affiliated Hospital of Sun Yat-sen University between December 2016 and December 2018 were enrolled in the present study. Reverse transcription-quantitative PCR (RT-qPCR) was performed to measure NEAT1 expression level in tissue samples from patients with POF and healthy controls. Transient transfections were performed on two normal Chinese hamster ovary cell lines Lec8 and CHO, followed by RT-qPCR and western blot to evaluate gene interaction. Flow cytometry was performed to assess cell apoptosis. The results from the present study demonstrated that NEAT1 expression in ovarian tissues was significantly downregulated in patients with POF compared with healthy controls. Furthermore, the expression of p53 was upregulated in ovarian tissues from patients with POF compared with healthy controls and was inversely associated with NEAT1 expression. In hamster ovary cells, overexpression of NEAT1 led to inhibition of p53, whereas NEAT1 knockdown promoted the expression of p53. In addition, ovary cell apoptosis was inhibited following NEAT1 overexpression and stimulated following p53 overexpression. In conclusion, overexpression of NEAT1 may inhibit the expression of p53 and improve premature ovarian failure.

miR-92a promotes progesterone resistance in endometriosis through PTEN/AKT pathway.

The alteration of PTEN expression may be a vital part of the pathological and physiological mechanisms in infertility-related with endometriosis. However, the potential mechanisms underlying abnormal expression of PTEN and its role in progesterone-resistant endometriosis have not been thoroughly elucidated. In this study, our data showed the PTEN messenger RNA (mRNA) level and protein expression was reduced in progesterone-resistant endometriosis tissue and primary stomal cells. Low levels of PTEN in endometrial stromal cells led to higher cell proliferation and resistance to progesterone. In terms of PTEN suppression in progesterone-resistant endometriosis, the mRNA level of miR-92a was correlated negatively with PTEN level. Transfection of miR-92a mimic reduced PTEN expression and made the stromal cells more resistant to progesterone treatment. Inhibition of miR-92a by its antagomir had the opposite effects. Results of the luciferase reporter assay for the 3'-nontranslated region suggested that miR-92a directly modulated PTEN levels. Moreover, miR-92a inhibition by its antagomir enhanced the therapeutic effect of progesterone, which suppressed stromal cell proliferation, and reduced the formation of ectopic lesions in the mouse model of endometriosis. Hence, this study revealed that miR-92a contributed to the development of progesterone resistant endometriosis by suppression of PTEN expression, and modulation of miR-92a might be a potential medical method of treating endometriosis.

Intrauterine infusion of platelet-rich plasma is a treatment method for patients with intrauterine adhesions after hysteroscopy.

OBJECTIVE: To evaluate the efficacy of an intrauterine infusion of platelet-rich plasma (PRP) in patients with intrauterine adhesions (IUAs). METHODS: A retrospective study was conducted from April 2018 to December 2019 to compare the efficacy of intrauterine infusion of PRP with balloon for patients with IUAs. All patients had moderate or severe IUAs, including 28 patients with intrauterine infusion of PRP (group A), 22 patients with intrauterine balloon (group B), and 20 patients with both intrauterine infusion of PRP and balloon in the first operative hysteroscopy. American Fertility Society (AFS) score and rates of chemical pregnancy were compared. RESULTS: The AFS score decreased with an average of 5.18 ± 3.93, 4.91 ± 4.39, and 5.15 ± 3.17 comparing the third hysteroscopy with the first operative hysteroscopy in group A, group B, and group C, respectively. No significant differences were found among these groups (P=0.734). The rates of chemical pregnancy were 40.0% in group A, 38.9% in group B, and 33.3% in group C without significant differences (P=0.944). CONCLUSION: There were no significant differences between intrauterine infusion of PRP and balloon. PRP is a treatment method for IUAs.

HNF1A inhibition induces the resistance of pancreatic cancer cells to gemcitabine by targeting ABCB1.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor prognosis, and gemcitabine-based chemotherapy remains an effective option for the majority of PDAC patients. Hepatocyte nuclear factor 1α (HNF1A) is a tumor-suppressor in PDAC, but its role in gemcitabine chemoresistance of PDAC has not been clarified. METHODS: The function of HNF1A in gemcitabine was detected by overexpression and knockdown of HNF1A in vitro and in vitro. The regulatory network between HNF1A and ABCB1 was further demonstrated by luciferase assays, deletion/mutation reporter construct assays and CHIP assays. FINDINGS: Here, we found that HNF1A expression is significantly associated with gemcitabine sensitivity in PDAC cell lines. Moreover, we identified that HNF1A overexpression enhanced gemcitabine sensitivity of PDAC both in vitro and in vitro, while inhibition of HNF1A had the opposite effect. Furthermore, by inhibiting and overexpressing HNF1A, we revealed that HNF1A regulates the expression of MDR genes (ABCB1 and ABCC1) in PDAC cells. Mechanistically, we demonstrated that HNF1A regulates ABCB1 expression through binding to its specific promoter region and suppressing its transcription levels. Finally, the survival analyses revealed the clinical value of HNF1A in stratification of gemcitabine sensitive pancreatic cancer patients. INTERPRETATION: Our study paved the road for finding novel treatment combinations using conventional cytotoxic agents with functional restoration of the HNF1A protein, individualized treatment through HNF1A staining and improvement of the prognosis of PDAC patients. FUND: National Natural Science Foundations of China and National Natural Science Foundation of Guangdong Province.

ARRDC1 and ARRDC3 act as tumor suppressors in renal cell carcinoma by facilitating YAP1 degradation.

The α-arrestins domain-containing 1 and 3 (ARRDC1 and ARRDC3) are two members of the α-arrestins family. Yes-associated protein 1 (YAP1) is a key downstream transcription co-activator of the Hippo pathway essential for cancer initiation, progression, or metastasis in clear cell renal cell carcinoma (ccRCC). The aim of this work was to elucidate the role of the α-arrestins in ccRCC tumorigenesis by identifying molecular interacting factors and exploring potential mechanisms. In this study, we identified YAP1 as a novel ARRDC3 interacting protein in RCC cells through tandem affinity purification and mass spectrometry. We confirmed that ARRDC1 and ARRDC3, but not other α-arrestin family proteins, interact with YAP1. Binding of ARRDC1/3 to YAP1 is mediated through the WW domains of YAP1 and the PPXY motifs of ARRDC1/3. Functional analysis of ARRDC1/3 by lentiviral shRNA revealed a role for ARRDC1/3 in suppression of cell growth, migration, invasion and epithelial-mesenchymal transition in ccRCC cells, and these effects were mediated, at least in part, through YAP1. Mechanically, ARRDC1/3 negatively regulates YAP1 protein stability by facilitating E3 ubiquitin ligase Itch-mediated ubiquitination and degradation of YAP1. Moreover, ARRDC1/3 mRNA levels were significantly downregulated in ccRCC specimens. A negative correlation was identified between ARRDC3 and YAP1 expression in ccRCC specimens by immunohistochemistry. This study revealed a novel mechanism for ARRDC1/3 in the regulation of YAP1 stability and provided insight in understanding the relationship between ARRDC1/3 downregulation and aberrant Hippo-YAP1 pathway activation in ccRCC.

Surgical interventions for gastric cancer: a review of systematic reviews.

AIM: To evaluate methodological quality and the extent of concordance among meta-analysis and/or systematic reviews on surgical interventions for gastric cancer (GC). METHODS: A comprehensive search of PubMed, Medline, EMBASE, the Cochrane library and the DARE database was conducted to identify the reviews comparing different surgical interventions for GC prior to April 2014. After applying included criteria, available data were summarized and appraised by the Oxman and Guyatt scale. RESULTS: Fifty six reviews were included. Forty five reviews (80.4%) were well conducted, with scores of adapted Oxman and Guyatt scale ≥ 14. The reviews differed in criteria for avoiding bias and assessing the validity of the primary studies. Many primary studies displayed major methodological flaws, such as randomization, allocation concealment, and dropouts and withdrawals. According to the concordance assessment, laparoscopy-assisted gastrectomy (LAG) was superior to open gastrectomy, and laparoscopy-assisted distal gastrectomy was superior to open distal gastrectomy in short-term outcomes. However, the concordance regarding other surgical interventions, such as D1 vs. D2 lymphadenectomy, and robotic gastrectomy vs. LAG were absent. CONCLUSION: Systematic reviews on surgical interventions for GC displayed relatively high methodological quality. The improvement of methodological quality and reporting was necessary for primary studies. The superiority of laparoscopic over open surgery was demonstrated. But concordance on other surgical interventions was rare, which needed more well-designed RCTs and systematic reviews.

ASPP1/2-PP1 complexes are required for chromosome segregation and kinetochore-microtubule attachments.

Regulated interactions between kinetochores and spindle microtubules are critical for maintaining genomic stability during chromosome segregation. Defects in chromosome segregation are widespread phenomenon in human cancers that are thought to serve as the fuel for tumorigenic progression. Tumor suppressor proteins ASPP1 and ASPP2, two members of the apoptosis stimulating proteins of p53 (ASPP) family, are frequently down-regulated in human cancers. Here we report that ASPP1/2 are required for proper mitotic progression. In ASPP1/2 co-depleted cells, the persistence of unaligned chromosomes and the reduction of tension across sister kinetochores on aligned chromosomes resulted in persistent spindle assembly checkpoint (SAC) activation. Using protein affinity purification methods, we searched for functional partners of ASPP1/2, and found that ASPP1/2 were associated with a subset of kinetochore proteins (Hec1, KNL-1, and CENP-F). It was found that ASPP1/2 act as PP1-targeting subunits to facilitate the interaction between PP1 and Hec1, and catalyze Hec1 (Ser165) dephosphorylation during late mitosis. These observations revealed a previously unrecognized function of ASPP1/2 in chromosome segregation and kinetochore-microtubule attachments that likely contributes to their roles in chromosome stability and tumor suppression.