Reproduction

Yang, Xiao; Li, Muzi; Xu, Zihan; Jiang, Qi; Du, Yanbo; Lv, Hong; Yan, Lei

doi: 10.1530/rep-24-0232pmid: 39679898

In briefAberrant lipid metabolism and dysregulated apoptosis in granulosa cells (GCs) may contribute to diminished ovarian reserve in patients with polycystic ovary syndrome (PCOS). This article elucidates the pivotal role played by S100A11.AbstractApoptosis of ovarian GCs affects the development and maturation of oocyte in PCOS. The objective of our study was to examine the impact of S100A11 on GCs in individuals with polycystic ovary syndrome. We found that the S100A11 level was higher in the ovarian GCs of PCOS patients and ovarian tissue of PCOS mouse models. S100A11 overexpression experiments demonstrated a decrease in the cell proliferation, upregulating the apoptosis and blocking the cell cycle. Immunofluorescence staining showed that S100A11 proteins were mainly located in the nucleus. Integrating the RNA-seq and ChIP-seq, this study found that S100A11 mainly regulated the genetic transcription and lipid metabolism. Furthermore, lipid accumulation and increasing oxidative stress were detected in the S100A11 overexpression group. We also revealed that S100A11 upregulated the p-DRP1 Ser616 to induce the mitochondrial fission. In conclusion, S100A11 upregulated the phospho-DRP1 to activate ovarian GC apoptosis and induced the lipid metabolism and oxidative stress to regulate the follicular reserve in PCOS. Our study provides a functional link between S100A11 expression and apoptosis and lipid metabolism in PCOS, providing new insights into disease mechanisms.

Roberts, Emily R; Ganeshkumar, Sornakala; Gunewardena, Sumedha; Chennathukuzhi, Vargheese

doi: 10.1530/rep-24-0344pmid: 39679867

In briefPRICKLE1, a WNT/planar cell polarity (PCP) protein that is downregulated in uterine leiomyoma, plays an important role in myometrial tissue architecture and extracellular matrix (ECM) deposition. This paper shows that myometrial-specific ablation of the mouse Prickle1 gene results in a uterine leiomyoma phenotype.AbstractUterine leiomyomas (ULs) are the most prevalent benign tumors of the female reproductive tract, originating from the myometrium and affecting over 75% of reproductive-age women. Symptoms of UL include pelvic pain, pressure, dysmenorrhea, menorrhagia, anemia and reproductive dysfunction. Currently, there is no effective long-term pharmacotherapy for UL, making them the leading cause of hysterectomies in the United States. The lack of treatment options is attributed to the absence of accurate animal models and a limited understanding of UL pathogenesis. Previous research has shown that the loss of repressor of element 1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) within the myometrium promotes UL pathogenesis. In addition, deletion of Rest in the mouse myometrium leads to a UL phenotype. PRICKLE1, also known as Rest-interacting LIM-domain protein (RILP), is required for nuclear localization of REST and Wnt/PCP signaling, making it a critical target for UL studies. In the context of PCP, smooth muscle cells in UL show abnormal organization, aberrant ECM structure and expression levels, potentially influenced by PRICKLE1 loss. The exact role of PRICKLE1 and Wnt/PCP in UL pathogenesis remains unclear. To explore PRICKLE1’s role in UL, we deleted Prickle1 using our myometrial-specific iCre. Our findings demonstrate that Prickle1 loss in the myometrium results in a UL phenotype characterized by altered collagen expression, excessive ECM deposition, aberrant smooth muscle cell organization, increased Esr1 and Pgr expression and dysregulated Wnt/PCP signaling. This novel mouse model serves as a valuable preclinical tool for understanding UL pathogenesis and developing future pharmacotherapies.

Yu, Haotian; Shi, Yan; Wu, Xiaotong; Hu, Bingjie; Jin, Hao; Kassim, Yassin; Iqbal, Tariq; Kandil, Omaima Mohamed; Ismail, Esraa Aly; Wang, Huanan; Wang, Shaohua; Zhang, Kun

doi: 10.1530/rep-24-0307pmid:

Gaidamaka, Anna O; Alexandrova, Alena D; Chermnykh, Elina S; Starinnov, Zakhar R; Sabirov, Marat S; Silaeva, Yulia Y; Vorotelyak, Ekaterina A

doi: 10.1530/rep-24-0375pmid: 39704695

In briefBecause the study of endometrial stem or progenitor cells has focused more on their potential ability to repair the endometrium, it is necessary to investigate their role in preparing the tissue for embryo implantation. Therefore, we selected CD90 protein as a marker of the population of cells with progenitor properties to study their contribution to hormone-regulated endometrial processes.AbstractThe endometrium is a dynamic tissue that undergoes significant changes during the reproductive cycle and pregnancy. Its high regenerative capacity is because of the presence of progenitor cells, which maintain tissue homeostasis. Previous studies have identified small populations of endometrial progenitor cells and investigated their role in tissue repair. However, the involvement of these cells in hormone-mediated changes in the endometrial stroma during decidualization and implantation has not been fully understood. In this study, we used CD90 as a potential marker for endometrial progenitor cells. We demonstrated that CD90+ cells have a higher clonogenicity and lower proliferative potential than CD90−. The localization of this marker around the embryo during decidualization led us to hypothesize that CD90+ cells may be directly involved in preparing the endometrial stroma for implantation. The results demonstrated an increase in the percentage of CD90+ cells in the endometrium of pregnant mice compared with nonpregnant mice. Additionally, the embryos exhibited a greater ability to spread on CD90+ cells in vitro. Our data support the hypothesis that CD90+ cells play a functional role in implantation, although the exact hormone-dependent mechanisms require further investigation. Based on the subluminal localization of CD90+ cells, we suggested that the luminal epithelium maintains a CD90+ cell surface phenotype. Consequently, we established epithelial–mesenchymal organoids, and the localization of CD90 in these organoids resembled that observed in vivo. Overall, CD90+ cells demonstrate high clonogenicity and contribute to the preparation of the stroma for interaction with the embryo during the implantation process.

Chen, Si-Man; Liu, Yu-Kai; Ma, Xiao-Qian; Wei, Chun-Yan; Li, Ming-Qing; Zhu, Xiao-Yong

doi: 10.1530/rep-24-0278pmid: 39679878

In briefEndometriosis (EM) is a chronic inflammatory disease with unclear pathogenesis, in which peritoneal macrophages play a pivotal role. This study demonstrates that creatine (CR) induces M2 polarization of peritoneal macrophages, promoting angiogenesis, fibrogenesis and lesion progression in EM, offering new insight into potential therapeutic strategies.AbstractEM is a chronic inflammatory disease characterized by the growth of endometrium-like tissues outside the uterine cavity, with an unclear pathogenesis. The analysis of single-cell sequencing data revealed the pivotal role of peritoneal macrophages in the development of EM. We noted significant CR enrichment and synthesis in peritoneal macrophages of patients with EM compared with women without EM. To further investigate the mechanisms of CR in EM, we performed RNA sequencing and in vitro experiments. We found that CR reprograms M2 polarization by enhancing matrix metalloproteinases and anti-inflammatory cytokines, which are involved in angiogenesis, fibrogenesis, cell adhesion and tissue repair. The coculture of CR-treated macrophages promoted the migration and fibrogenesis of endometrial stromal cells, as well as the angiogenesis of HUVECs in vitro. In summary, this article reveals that CR might polarize M2 macrophages, promoting the initiation, fibrosis and angiogenesis of ectopic endometrial lesions, ultimately resulting in the development of EM. These findings underscore the crucial immunomodulatory role of CR in the pathogenesis of EM, offering a promising target for therapeutic intervention.