New models of lipopolysaccharide‐induced implantation loss reveal insights into the inflammatory response

Abstract

Problem Chronic endometritis, inflammation of the uterizzvvne lining caused by common gram‐negative bacterial strains or mycoplasma, has been associated with unexplained implantation failure and infertility. However, limited models of bacteria‐induced implantation loss exist to study the molecular changes that occur in vivo. The goal of this study was to provide a new resource to study the process of bacteria‐induced inflammation and implantation loss utilizing common experimental models: C57Bl/6 mice and primary human endometrial stromal cells. Method of study Prior to implantation, mated C57Bl/6 females were administered vehicle (saline) or gram‐negative bacterial lipopolysaccharide (LPS) at a range of concentrations by intraperitoneal injection. Implantation sites were counted, and uteri were harvested to evaluate the molecular changes that accompany LPS‐mediated implantation loss. Primary human endometrial stromal cells were decidualized in vitro in the presence and absence of LPS. Total RNA and conditioned media were harvested to evaluate the expression of known decidualization‐associated genes and various cytokines and chemokines. Results Lipopolysaccharide treatment resulted in fewer implantation sites in mice, decreased expression of decidualization‐associated genes, and altered expression and release of cytokines and chemokines. Immunohistological analysis of the uterus from LPS‐exposed mice demonstrated increased apoptosis and decreased proliferation during decidualization. Conclusion Lipopolysaccharide exposure disrupted implantation and decidualization in mice and human endometrial stromal cells. This model could be used to study the pathophysiology of implantation failure in patients with chronic endometritis or to test potential therapeutic interventions.

Delayed Antiviral Immune Responses in Severe Acute Respiratory Syndrome Coronavirus Infected Pregnant Mice

“…Together, it indicated that implantation accompanies an intricacy inflammatory regulatory net between the blastocysts and maternal uterus, even maternal immune system. Besides, implantation loss in female mice caused by intraperitoneal injection of lipopolysaccharide (LPS) indicates that inflammation changes can impair the inflammatory state of the uterus during the implantation window (Moustafa et al, 2019). In male mice, the SARS-CoV-2 infection could disrupt the blood-testis barrier through the induction of inflammatory cytokines and disruption of junctional protein rather than directly invading the target cells (Peirouvi et al, 2021).…”

Detrimental effects of lipopolysaccharide on the attachment and outgrowth of various trophoblastic spheroids on human endometrial epithelial cells

“…It has been shown that implantation failure is induced by LPS through stimulation of the innate immune system and activation of the TLR4 pathway in the early stages of pregnancy [11,33]. A similar study suggested that TLR3 stimulated by a synthetic ligand, poly I: C (which is a double-stranded RNA molecule) in CBA/J female mice increased fetal losses [34] and reduced actin polymerization and adhesion molecule expression in endometrial cells [35].…”

“…LPS is an antigen that induces immune responses in uterine endometrial cells by TLR4 activation. LPS can trigger an imbalance in cytokines in the uterine endometrium [11,12].…”

Oil‐based contrast for hysterosalpingography‐regulated Th1/Th2‐type cytokines and alleviated inflammation in rats with LPS‐induced chronic endometritis

“…18 Moustafa showed a new model of LPS-induced implantation loss and found that LPS exposure occurring prior to implantation and decidualization resulted in stark changes in the mouse endometrium. 19 Wu generated a mouse rat model of endometritis induced by the local injection of 40 μg LPS into the uterus; after 48 h, neutrophil counts indicated a significant increase in the mouse endometrium after the injection of 30 or 40 μg LPS. 15 Endometritis is subdivided into two categories: acute endometritis is symptomatic and characterized by microabscess formation and neutrophil invasion in the endometrial superficial epithelium, gland lumina, and uterine cavity, and CE is rather silent without obvious clinical manifestations and is characterized by unusual plasmacyte infiltration into endometrial stromal areas.…”