The epithelial-to-mesenchymal transition may play a role in adenomyosis. GRIM19 expression is downregulated in adenomyotic lesions, and the effects of this downregulation in adenomyosis remain relatively unclear. In this study, we aimed to explore whether aberrant GRIM19 expression is associated with the epithelial-to-mesenchymal transition in adenomyosis and found that the expression of both GRIM19 and WT1 was low, and epithelial-to-mesenchymal transition, which included significant changes in CDH1, CDH2 and KRT8 expression, occurred in adenomyotic lesions, as confirmed by Western blotting and quantitative real-time PCR. We provided novel insights into WT1 expression in adenomyosis, revealing that WT1 expression was increased in the endometrial glands of adenomyotic lesions by immunohistochemistry. In vitro, knockdown of GRIM19 expression by small interfering RNA (siRNA) promoted the proliferation, migration and invasion of Ishikawa cells, as measured by Cell Counting Kit-8, wound healing assay and Transwell assays. Western blotting and quantitative real-time PCR confirmed that WT1 expression increased and epithelial-to-mesenchymal transition was induced, including the upregulation of CDH2 and downregulation of CDH1 and KRT8after transfecting the GRIM19 siRNA to Ishikawa cells. Furthermore, Wt1 expression was upregulated and epithelial-to-mesenchymal transition was observed, including downregulation of Cdh1 and Krt8 in Grim19 gene-knockdown mice. Upregulation of Wt1 expression in the endometrial glands of Grim19 knockdown mice was also verified by immunohistochemistry. Taken together, these results reveal that low expression of GRIM19 in adenomyosis may upregulate WT1 expression and induce epithelial-to-mesenchymal transition in the endometria, providing new insights into the pathogenesis of adenomyosis.
Artificial intelligence (AI) has experienced rapid growth over the past few years, moving from the experimental to the implementation phase in various fields, including medicine. Advances in learning algorithms and theories, the availability of large datasets and improvements in computing power have contributed to breakthroughs in current AI applications. Machine learning (ML), a subset of AI, allows computers to detect patterns from large complex datasets automatically and uses these patterns to make predictions. AI is proving to be increasingly applicable to healthcare, and multiple machine learning techniques have been used to improve the performance of assisted reproductive technology (ART). Despite various challenges, the integration of AI and reproductive medicine is bound to give an essential direction to medical development in the future. In this review, we discuss the basic aspects of AI and machine learning, and we address the applications, potential limitations and challenges of AI. We also highlight the prospects and future directions in the context of reproductive medicine.
Embryo implantation is a complex process involving synchronised crosstalk between a receptive endometrium and functional blastocysts. Apoptosis plays an important role in this process as well as in the maintenance of pregnancy. In this study, we analysed the expression pattern of programmed cell death 4 (Pdcd4), a gene associated with apoptosis in the mouse endometrium, during early pregnancy and pseudopregnancy by real-time quantitative polymerase chain reaction, in situ hybridisation, Western blotting and immunohistochemistry. The results showed that Pdcd4 was increased along with days of pregnancy and significantly reduced at implantation sites (IS) from day 5 of pregnancy (D5). The level of Pdcd4 at IS was substantially lower than that at interimplantation sites (IIS) on D6 and D7. In addition, Pdcd4 expression in the endometrium was reduced in response to artificially induced decidualisation in vivo and in vitro. Downregulation of Pdcd4 gene expression in cultured primary stromal cells promoted decidualisation, while upregulation inhibited the decidualisation process by increasing apoptosis. These results demonstrate that Pdcd4 is involved in stromal cell decidualisation by mediating apoptosis and therefore plays a role in embryo implantation in mice.
Xiaoyu YangCollege of Preclinical Medicine, Fujian Medical University, Fuzhou, People’s Republic of China The Affiliated Fuzhou First Hospital, Fujian Medical University, Fuzhou, People’s Republic of China Fuzhou Maternity and Child Health Care Hospital, Fuzhou, People’s Republic of China
Vitrification of embryos is a routine procedure in IVF (in vitro fertilization) laboratories. In the present study, we aimed to investigate the effect of vitrification on mouse preimplantation embryo development in vitro, and effect on the epigenetic status of imprinted gene Grb10 in mouse embryos. The blastocyst formation rate for vitrified 8-cell embryos was similar to the non-vitrified 8-cell embryos, whereas the blastocyst hatching rate was lower than that of the non-vitrified group. The expression level of Grb10 major-type transcript decreased significantly in vitrified blastocysts compared with non-vitrified and in vivo blastocysts. Moreover, the global DNA methylation level in 8-cell embryos and blastocysts, and the DNA methylation at CpG island 1 (CGI1) of Grb10 in blastocysts were also significantly decreased after vitrification. In vitro culture condition had no adverse effect, except for on the DNA methylation in Grb10 CGI1. These results suggest that vitrification may reduce the in vitro development of mouse 8-cell embryos and affect the expression and DNA methylation of imprinted gene Grb10.
Qitao HuangDepartment of Obstetrics and Gynecology, First People's Hospital of Foshan, Foshan, Guangdong, China Division of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China
Fang HeDepartment of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Engineering and Technology Research Center of Maternal-Fetal Medicine, Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Wenyan GengDepartment of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Engineering and Technology Research Center of Maternal-Fetal Medicine, Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Dunjin ChenDepartment of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Engineering and Technology Research Center of Maternal-Fetal Medicine, Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Placenta accreta spectrum (PAS) has an urgent need for reliable prenatal biomarkers. This study profiled the circular RNAs (circRNAs) in PAS placenta and maternal blood and identified two circRNAs can regulate trophoblast cells invasion and serve as noninvasive prenatal biomarkers for PAS prediction.
PAS is one of the most alarming obstetric diseases with high mortality rates. The regulating mechanism underlying PAS remains to be investigated, and reliable blood biomarkers for PAS have not emerged. Circular RNAs (circRNAs) have become important regulators and biomarkers for disparate human diseases. However, the circRNA profiles of PAS were not reported, and the regulatory role and predictive value of circRNAs in PAS were unknown. Here, we comprehensively profiled the circRNAs in the placenta of PAS by transcriptome sequencing and analysis and uncovered 217 abnormally expressed circRNAs. Through competing endogenous RNA network analysis, we found that the target genes of upregulated circRNAs in PAS were enriched in placenta development-related pathways and further uncovered two circRNAs, circPHACTR4 and circZMYM4, that could regulate trophoblast cells invasion and migration in vitro. Finally, we verified that circPHACTR4 and circZMYM4 were also upregulated in the maternal peripheral blood of PAS women before delivery using transcriptome sequencing and RT-qPCR and evaluated their predictive value by ROC curves. We found that circPHACTR4 and circZMYM4 could serve as effective predicting biomarkers for PAS (area under the curve (AUC): 0.86 and 0.85) and propose an improved model for PAS prenatal prediction by combining the conventional ultrasound diagnosis with the new circRNA predictive factors (AUC: 0.91, specificity: 0.89, sensitivity: 0.82).Altogether, this work provides new resources for deciphering the biological roles of circRNAs in PAS, identified two circRNAs that could regulate trophoblast cells invasion during placentation, and revealed two noninvasive diagnostic markers for PAS.