As a multifaceted adipokine, chemerin has been found to perform functions vital for immunity, adiposity, and metabolism through its three known receptors (chemokine-like receptor 1, CMKLR1; G-protein-coupled receptor 1, GPR1; C-C motif chemokine receptor-like 2, CCRL2). Chemerin and the cognate receptors are also expressed in the hypothalamus, pituitary gland, testis, ovary, and placenta. Accumulating studies suggest that chemerin participates in normal reproduction and underlies the pathological mechanisms of certain reproductive system diseases, including polycystic ovary syndrome (PCOS), preeclampsia, and breast cancer. Herein, we present a comprehensive review of the roles of the chemerin system in multiple reproductive processes and human reproductive diseases, with a brief discussion and perspectives on future clinical applications.

Ovarian endometrioma (OEM), a particularly severe form of endometriosis, is an oestrogen‐dependent condition often associated with pain and infertility. The mechanisms by which OEM impairs fertility, particularly through its direct impact on oocyte‐cumulus cell (CC) communication and related pathways, remain poorly understood. This study investigates the impact of OEM on oocyte‐CC communication and explores melatonin's therapeutic potential. We used a mouse model of OEM and employed ovarian transcriptome and gene set enrichment analyses to identify disrupted gene pathways, alongside phalloidin staining for cytoskeletal analysis, gap junction coupling analysis for intercellular communication, and mitochondrial function assessments for cellular metabolism. Our results showed that OEM significantly impairs steroidogenesis and cumulus cell function, leading to increased apoptosis, disrupted transzonal projections (TZPs), and impaired antioxidant transfer to oocytes. This culminates in oxidative stress, mitochondrial dysfunction, and compromised ATP production. OEM oocytes also exhibited severe abnormalities, including DNA damage, maturation defects, spindle assembly disruptions, and increased aneuploidy. This study identifies disrupted TZPs as a key pathological feature in OEM and highlights melatonin's potential to restore intercellular communication, mitigate oxidative damage, and improve reproductive outcomes.

Embryo implantation requires synergistic interaction between the embryo and the receptive endometrium. Glycoproteins and glycan-binding proteins are involved in endometrium-embryo attachment. Sialyl Tn (sTn), a truncated O-glycan, is catalyzed by ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) and can be detected by specific Sialic-acid-binding immunoglobulin-like lectins (Siglecs). Whether the sTn-Siglecs axis supports embryo implantation remains unknown. This paper aims to study the role of ST6GALNAC1/sTn-Siglecs axis in embryo implantation. ST6GALNAC1 and sTn in human endometrium were analyzed by immunohistochemistry. An in vitro implantation model was conducted to evaluate the effects of ST6GALNAC1/sTn on the receptivity of human endometrial AN3CA cells to JAR spheroids. Immunoprecipitation combined with mass spectrometry analysis was carried out to identify the key proteins modified by sTn in endometrial cells. Siglec-6 in human embryos was analyzed by published single-cell RNA sequencing (scRNA-seq) datasets. Protein interaction assay was applied to verify the bond between the Siglec-6 with sTn-modified CD44. St6galnac1 siRNAs and anti-sTn antibodies were injected into the uterine horn of the mouse at the pre-implantation stage to evaluate the role of endometrial St6galnac1/sTn in embryo implantation. Siglec-G in murine embryos was analyzed by immunofluorescence staining. The function of Siglec-G is evidenced by uterine horn injection and protein interaction assay. Both human and murine endometrium at the receptive stage exhibit higher ST6GALNAC1 and sTn levels compared to the non-receptive stage. Overexpression of ST6GALNAC1 significantly enhanced the receptivity of AN3CA cells to JAR spheroids. Inhibition of endometrial ST6GALNAC1/sTn substantially impaired embryo implantation in vivo. CD44 was identified as a carrier for sTn in the endometrial cells of both species. Siglec-6 and Siglec-G, expressed in the embryonic trophectoderm, were found to promote embryo attachment, which may be achieved through binding with sTn-modified CD44. ST6GALNAC1-regulated sTn in the endometrium aids in embryo attachment through interaction with trophoblastic Siglecs.

Ovarian endometriosis (OEM) is a chronic inflammatory condition that impairs ovarian function. While its effects on ovarian reserve are well established, the long-term consequences of OEM on ovarian dysfunction, premature ovarian failure (POF), and systemic health, particularly in the context of accelerated aging, remain insufficiently studied. In this study, we employed an OEM mouse model and bulk RNA sequencing to investigate the underlying mechanisms. Our results show that OEM accelerates primordial follicle depletion and upregulates mTOR signaling pathway gene expression, along with mechanical stress and paracrine signaling via the Hippo and Myc pathways. OEM also induces irregular estrus and ovarian fibrosis in aging mice, decreases serum AMH levels, and increases FSH levels. Systemically, elevated serum IgG levels contribute to osteoporosis and cognitive decline, both linked to ovarian dysfunction and POF in OEM. These findings elucidate the mechanisms driving premature ovarian reserve depletion in OEM and highlight its broader systemic effects. This study emphasizes the importance of monitoring ovarian health and ectopic tissue to safeguard ovarian reserves and mitigate long-term risks such as osteoporosis and cognitive decline.

Endometriosis affects nearly 10 % of reproductive-age women and is characterized by the growth of endometrial-like tissues outside the uterus. This disease poses significant diagnostic and therapeutic challenges due to its unknown origins and complex pathophysiology. Our study investigates how epithelial-mesenchymal transition (EMT) contributes to the dysregulation of estradiol metabolism by suppressing hydroxysteroid 17β dehydrogenase 2 (HSD17B2) expression in endometriotic epithelial cells. We used Gene Set Variation Analysis (GSVA) on public microarray data to correlate EMT scores with HSD17B2 levels. This approach revealed a significant correlation, showing that EMT is linked to reduced HSD17B2 expression in endometriotic tissues. Furthermore, our qPCR and immunoblotting results showed that TGF-β-induced EMT significantly reduced HSD17B2 expression in human endometriotic 12Z epithelial cells. Additionally, our data showed that Snail, an EMT-related transcription factor, acts on the E-box motif in the HSD17B2 promoter to suppress transcription. Our findings show that EMT is associated with decreased HSD17B2 expression in endometriotic tissues. This downregulation disrupts estradiol metabolism, possibly contributing to endometriosis pathogenesis. Our study offers critical insights into the molecular mechanisms of endometriosis and suggests that targeting EMT, especially the TGF-β/Snail axis, could provide a new therapeutic approach.