Gram‐Negative Bacterial LPS Induced Poor Uterine Receptivity andImplantation Failure in Mouse: Alterations in IL‐1β Expression in the Preimplantation Embryo and Uterine Horns

Abstract

Genito-urinary tract or systemic infections of the gram-negative bacteria in pregnant women, causes abortions, preterm labor, and several other perinatal complications. LPS is the most potent antigenic component of the gram-negative bacterial cell wall and is known to modulate the expression of various proinflammatory cytokines. Here we investigate the role of the soluble form of IL-1 i.e., IL-1beta in the 'minimum dose' of LPS induced pregnancy loss in mice. Uterine cross-sections on each day of the preimplantation period of pregnancy were examined histopathologically for finding out LPS induced changes in the uterine preparation for embryo implantation. The expression of IL-1beta in the various stages of the preimplantation period of pregnancy was studied by RT-PCR in the embryos and the uterine horns of the LPS treated and normal pregnant mice. We found that LPS significantly alters the proliferation of the glandular epithelium, luminal epithelium and stroma during the preimplantation period. We also found large infiltration of macrophages into the uterine horns of the LPS treated animals. The level and pattern of IL-1beta expression in the preimplantation embryos and uterine horns were also altered in LPS treated animals. These observations indicate that LPS can alter the uterine preparation for blastocyst implantation, which could be due to the change in the IL-1beta expression in the uterine horns. However, a change in the expression pattern of IL-1beta in the preimplantation embryos underlines the significance of this molecule in LPS induced pregnancy loss or implantation failure in mouse.

Lipopolysaccharide induces alterations in ovaries and serum level of progesterone and 17β-estradiol in the mouse

“…Progesterone acts as immunomodulator at the maternal-fetal interface and plays a role in the survival of the fetus (28). Lipopolysaccharide treatment alters the expression of tumor necrosis factor-a (18), interleukin-1 (17,19), and colonystimulating factor-1 (16) and inhibits the implantation of the blastocyst (17), as reported previously. Cytokine-rich environments cause the generation of superoxide radicals in CL (29) and its regression, which may be responsible for the low level of P 4 during preimplantation days in LPS-treated animals.…”

“…We established a gram-negative bacterial infection model in the mouse in which the intraperitoneal injection of LPS (250 mg/kg body weight on day 0.5 of pregnancy) causes embryonic cell death (16) and leads to implantation failure on day 5.5 of pregnancy (17). Lipopolysaccharide causes an antifertility effect by altering expression of tumor necrosis factor-a (18), interleukin-1 (17,19), and colony-stimulating factor (16). Disturbance in embryonic and uterine secretion of these cytokines may trigger DNA damage in embryos (20,21) and uterine cells (21) during preimplantation days and leads to implantation failure in the mouse.…”

Effect of Bacterial Endotoxins on Superovulated Mouse Embryos In Vivo: Is CSF‐1 Involved in Endotoxin‐Induced Pregnancy Loss?

“…Park strain mice were maintained, superovulated, and mated as described earlier (Deb et al [9, 10]). Female mice were killed by cervical dislocation on days 1.5, 2.5, 3.5, 4.0, 4.125, 4.25, 4.3, and 4.42 of the preimplantation period of pregnancy.…”

Gonadal and nongonadal FSHR and LHR dysfunction during lipopolysaccharide induced failure of blastocyst implantation in mouse

“…The leading cause of infection-associated preterm labor is considered to be bacterial infections. Gram-negative bacterial lipopolysaccharide (LPS) response through toll-like receptor (TLR)-4 [24] and results in production of cytokines [5][6][7]11]. TLR-4 stimulation is also known to induce fetal resorption when it occurs in early pregnancy.…”