Biology subjects

Nallasamy, S.

Publications and source records attributed to Nallasamy, S..

3 recordsLinked to original sources

bioRxiv2025

Expression of Lysyl Oxidase Family Enzymes During Human Endometrial Decidualization

Lysyl oxidases (LOXs), comprising lysyl oxidase (LOX) and lysyl oxidase like 1-4 (LOXL1-4), constitute a highly conserved enzyme family. Their primary function is the crosslinking of collagen and elastic fibers, thereby modulating the structure and function of the extracellular matrix. Our primary objective was to elucidate the localization of LOXs within human endometrial tissues and to investigate the expression profile of LOXs during in vitro human endometrial stromal cell decidualization. Immunohistochemical localization revealed that all LOXs were expressed in human endometrium during both the proliferative and secretory phases of menstrual cycle. All five LOXs were expressed in human endometrial stromal cells cultured in vitro. Gene expression levels of LOX, LOXL1, and LOXL2 significantly decreased during endometrial stromal cell decidualization in vitro. In contrast, LOXL3 and LOXL4 gene expression remained unaffected. Protein levels of LOX, LOXL1, and LOXL3 also showed a significant reduction. Additionally, conditioned media analysis revealed abundant secretion and release of LOX and LOXL1-3 into the extracellular space at all time points examined, with their levels remaining constant. The primary targets of LOXs, collagen and elastic fibers, undergo significant synthesis and processing during endometrial stromal cell decidualization in vitro. This observation was supported by the differential gene expression levels of factors involved in their processing and assembly. Collectively, this study demonstrates the expression of LOXs in the human endometrium and their potential role in extracellular matrix reorganization during decidualization.

cell biology↗

bioRxiv2025

Extracellular Matrix Reorganization During Endometrial Decidualization

Extracellular matrix reorganization, a concurrent process of endometrial decidualization, has garnered widespread recognition. However, our understanding of this process remains limited. In this study, we aimed to investigate the expression, spatial distribution, and reorganization of fibrillar collagens, elastin, and lysyl oxidases within the decidua. Using second harmonic generation imaging, we successfully recorded fibrillar collagen reorganization between preimplantation and decidualized endometrium. Upon embryo implantation, the fibrillar collagens align themselves parallel to the direction of embryo invasion. Furthermore, we employed confocal imaging analysis to reveal distinct expression and spatial distribution patterns of elastin and lysyl oxidase-like enzymes. Elastin expression begins to manifest surrounding the implanting embryo, extends into the decidua, and exhibits a high concentration in the mesometrial region after gestation day 8. All lysyl oxidase-like enzymes are localized within the decidua, although they exhibit varying expression patterns. To gain further insights, we utilized an in vitro stromal cell decidualization model and provided compelling evidence that stromal cells serve as the primary source of the extracellular matrix components during endometrial decidualization. Additionally, we demonstrated that the genes encoding factors involved in the synthesis, processing, and assembly of fibrillar collagen and elastic fibers exhibit differential expression patterns during in vitro decidualization. Genes such as asporin, decorin, thrombospondin 2, fibulin 2, fibulin 5, and lysyl oxidase show significant induction during in vitro decidualization. In summary, our comprehensive analysis provides a detailed evaluation of the expression, spatial distribution, and reorganization of fibrillar collagens, elastin, and lysyl oxidases during the process of endometrial decidualization. Summary SentenceFibrillar collagen, elastic fibers, and lysyl oxidases, synthesized by endometrial stromal cells, exhibit distinct spatial distributions and reorganization patterns within the decidua during embryo implantation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/644728v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@11314c1org.highwire.dtl.DTLVardef@1b7ae54org.highwire.dtl.DTLVardef@1641feorg.highwire.dtl.DTLVardef@146b1b8_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2024

Lysyl Oxidases are Necessary for Myometrial Contractility and On-Time Parturition in Mice

The extracellular matrix (ECM) plays a pivotal role in the maintenance of tissue mechanical homeostasis. Collagens and elastic fibers are the most predominant fibrous ECM proteins providing tissue mechanical function through covalent cross-linking which is mediated by the lysyl oxidase family of enzymes. In this study, the function of lysyl oxidases in maintaining the integrity of the extracellular matrix in the myometrium and its impact on parturition-timing was investigated. Gene and protein expression analyses demonstrate that a sub-set of the lysyl oxidase family of enzymes are highly induced in pregnant myometrium. Inhibition of the activity of the lysyl oxidase family of enzymes through {beta}-aminopropionitrile (BAPN) delays parturition in mice, in part, due to myometrial dysfunction. In BAPN treated mice, the expression of genes encoding contraction associated proteins such as connexin 43, oxytocin receptor and prostaglandin synthase 2 is significantly reduced in the myometrium compared to the untreated control mice. Proteomic analysis revealed that the composition of the ECM is altered in response to BAPN treatment which demonstrates that the inhibition of the activity of lysyl oxidases disrupted the integrity of the myometrial ECM. Our findings demonstrate that the lysyl oxidases-mediated ECM function is necessary for the myometrium to transition from a quiescent to a contractile phenotype at term for on-time parturition.

physiology↗