scholarly journals Gram-Negative Bacterial LPS Induced Poor Uterine Receptivity and Implantation Failure in Mouse: Alterations in IL-1β Expression in the Preimplantation Embryo and Uterine Horns

2005 ◽  
Vol 13 (3) ◽  
pp. 125-133 ◽  
Author(s):  
Kaushik Deb ◽  
Madan Mohan Chaturvedi ◽  
Yogesh Kumar Jaiswal
Keyword(s):  
Cross Sections ◽  
Pregnancy Loss ◽  
Embryo Implantation ◽  
Preimplantation Embryos ◽  
Soluble Form ◽  
Implantation Failure ◽  
Perinatal Complications ◽  
Uterine Receptivity ◽  
Gram Negative ◽  
Blastocyst Implantation

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-1β 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-1β 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-1β 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-1β expression in the uterine horns. However, a change in the expression pattern of IL-1β in the preimplantation embryos underlines the significance of this molecule in LPS induced pregnancy loss or implantation failure in mouse.

scholarly journals A ‘minimum dose’ of lipopolysaccharide required for implantation failure: assessment of its effect on the maternal reproductive organs and interleukin-1α expression in the mouse

Reproduction ◽  
2004 ◽  
Vol 128 (1) ◽  
pp. 87-97 ◽  
Author(s):  
Kaushik Deb ◽  
Madan M Chaturvedi ◽  
Yogesh K Jaiswal
Keyword(s):  
Pregnancy Loss ◽  
Biological Effects ◽  
Reproductive Organs ◽  
Implantation Failure ◽  
Gram Negative ◽  
Minimum Dose ◽  
Preimplantation Stage ◽  
Genital Tract Infections ◽  
Blastocyst Implantation ◽  
Tract Infections

Genital tract infections caused by gram-negative bacteria induce abortion and are one of the most common complications of human pregnancy. This study was carried out to decipher the mechanism of gram-negative bacterial lipopolysaccharide (LPS)-induced pregnancy loss, using a mouse (Park strain) model. Since many of the biological effects of LPS are mediated by interleukin (IL)-1α, the role of IL-1α in LPS-induced pregnancy loss was studied. Pregnant female animals were injected intra-peritoneally (i.p.) with different doses (1 to 50 μg) of LPS from Salmonella minnesota Re-595, on day 0.5 of pregnancy. We found that 250 μg/kg body weight (i.e. 5 μg/female mouse) of LPS when given on day 0.5 of pregnancy was the ‘minimum dose’ (MD) required to completely inhibit the implantation of the blastocyst in the mouse. The effect of this dose on the pathophysiology of the various reproductive organs (i.e. uterus, ectoplacental cones, developing fetus, ovaries etc.) was assessed on day 14 of pregnancy. The effects of this dose on the level and pattern of expression of the proinflammatory cytokine IL-1α in the maternal uterine horns and preimplantation stage embryos were studied by RT-PCR. A single dose (100 ng/mouse) of recombinant mouse IL-1α was given i.p. to pregnant females on day 1 of pregnancy to study its effect on implantation. Our results show that treatment of the pregnant animals with LPS may alter cell proliferation and induce leukocyte infiltration, degeneration of luminal glandular epithelium, and hyperplasia in the various reproductive organs, and may also alter both embryonic and uterine IL-1α expression. IL-1α administration also caused implantation failure similar to that of LPS. The observations suggest that the determined MD of LPS may alter the expression of developmentally important proinflammatory cytokines such as IL-1α, which could, in turn, inhibit the normal processes of blastocyst implantation. Therefore, it is proposed that the LPS-induced histopathological alterations in the various reproductive organs of pregnant animals could be mediated by IL-1α and this may be one of the causes of failure of blastocyst implantation in the mouse.

scholarly journals Uterine aquaporin expression is dynamically regulated by estradiol and progesterone and ovarian stimulation disrupts embryo implantation without affecting luminal closure

2020 ◽  
Vol 26 (3) ◽  
pp. 154-166 ◽  
Author(s):  
Vanessa de Oliveira ◽  
Jennifer Schaefer ◽  
Basim Abu-Rafea ◽  
George A Vilos ◽  
Angelos G Vilos ◽  
...  
Keyword(s):  
Embryo Development ◽  
Ovarian Stimulation ◽  
Embryo Implantation ◽  
Pathological State ◽  
Implantation Failure ◽  
Uterine Receptivity ◽  
Spatial Expression ◽  
Aqp4 Expression ◽  
Abnormal Expression ◽  
Aquaporin Gene

Abstract The study investigated the effect of normal and supraphysiological (resulting from gonadotropin-dependent ovarian stimulation) levels of estradiol (E2) and progesterone (P4) on mouse uterine aquaporin gene/protein (Aqp/AQP) expression on Day 1 (D1) and D4 of pregnancy. The study also examined the effect of ovarian stimulation on uterine luminal closure and uterine receptivity on D4 of pregnancy and embryo implantation on D5 and D7 of pregnancy. These analyses revealed that the expression of Aqp3, Aqp4, Aqp5 and Aqp8 is induced by E2 while the expression of Aqp1 and Aqp11 is induced by P4. Additionally, P4 inhibits E2 induction of Aqp3 and Aqp4 expression while E2 inhibits Aqp1 and Aqp11 expression. Aqp9, however, is constitutively expressed. Ovarian stimulation disrupts Aqp3, Aqp5 and Aqp8 expression on D4 and AQP1, AQP3 and AQP5 spatial expression on both D1 and D4, strikingly so in the myometrium. Interestingly, while ovarian stimulation has no overt effect on luminal closure and uterine receptivity, it reduces implantation events, likely through a disruption in myometrial activity and embryo development. The wider implication of this study is that ovarian stimulation, which results in supraphysiological levels of E2 and P4 and changes (depending on the degree of stimulation) in the E2:P4 ratio, triggers abnormal expression of uterine AQP during pregnancy, and this is associated with implantation failure. These findings lead us to recognize that abnormal expression would also occur under any pathological state (such as endometriosis) that is associated with changes in the normal E2:P4 ratio. Thus, infertility among these patients might in part be linked to abnormal uterine AQP expression.

Quantification of basigin mRNA in mouse oocytes and preimplantation embryos by competitive RT-PCR

Zygote ◽  
2002 ◽  
Vol 10 (3) ◽  
pp. 239-243 ◽  
Author(s):  
Nai-Zheng Ding ◽  
Cheng-Qiang He ◽  
Zeng-Ming Yang
Keyword(s):  
Embryo Implantation ◽  
Preimplantation Embryos ◽  
Immunoglobulin Superfamily ◽  
Competitive Polymerase Chain Reaction ◽  
Preimplantation Mouse Embryos ◽  
Preimplantation Mouse ◽  
Cell Embryo ◽  
Blastocyst Implantation ◽  
Polymerase Chain ◽  
High Level

Basigin is a member of the immunoglobulin superfamily and a key molecule related to mouse blastocyst implantation. Whether preimplantation mouse embryos express basigin mRNA is still unknown. The aim of this study was to use a quantitative competitive polymerase chain reaction to assess quantitatively the levels of basigin mRNA in mouse oocyte and preimplantation embryos. Basigin mRNA was detected in the oocyte and all the stages of preimplantation embryos. The levels of basigin mRNA were 0.0606 ± 0.0282 in the oocyte, 0.0102 ± 0.0036 in the zygote, 0.0007 ± 0.0003 in the 2-cell embryo, 0.0031 ± 0.0017 in the 4-cell embryo, 0.0084 ± 0.0024 in the 8-cell embryo, 0.0537 ± 0.0121 in the morula and 0.0392 ± 0.0161 attomoles in the blastocyst, respectively. The levels of basigin mRNA in the oocyte, morula and blastocyst were significantly higher than those in the zygote and embryos at the 2-cell, 4-cell and 8-cell stages. The high level of basigin expression in the blastocyst may play a role during embryo implantation.

Lipopolysaccharide-induced modulation in the expression of progesterone receptor and estradiol receptor leads to early pregnancy loss in mouse

Zygote ◽  
2012 ◽  
Vol 21 (4) ◽  
pp. 337-344 ◽  
Author(s):  
Varkha Agrawal ◽  
Mukesh Kumar Jaiswal ◽  
Yogesh Kumar Jaiswal
Keyword(s):  
Progesterone Receptor ◽  
Pregnancy Loss ◽  
Steroid Receptors ◽  
Gram Negative Bacteria ◽  
Implantation Failure ◽  
Early Pregnancy Loss ◽  
Chain Reaction ◽  
Gram Negative ◽  
Estradiol Receptor ◽  
Polymerase Chain

SummaryThe objective of the present study was to investigate the effect of Gram-negative bacteria infection on ovarian steroid receptors, i.e. progesterone receptor (PR) and estradiol receptor (ER) during preimplantation days of pregnancy. A well established mouse model of Gram-negative bacteria infection was used to test this objective. Mice were treated with normal saline or lipopolysaccharide (LPS) on day 0.5 of pregnancy and used to collect embryos and uterine horns on day 1.5 to day 4.42 preimplantation day of pregnancy. Total RNA was extracted and reverse-transcription polymerase chain reaction (PCR) was performed to check the expression of PR and ER genes. The mRNA expression of PR and ER was altered in embryos and uterus of LPS-treated animals during preimplantation days of pregnancy studied. These results suggest that PR and ER play an important role in Gram-negative bacteria infection and induced implantation failure in mouse.

scholarly journals Endometrial inflammation and effect on implantation improvement and pregnancy outcome

Reproduction ◽  
2012 ◽  
Vol 144 (6) ◽  
pp. 661-668 ◽  
Author(s):  
I Granot ◽  
Y Gnainsky ◽  
N Dekel
Keyword(s):  
Inflammatory Response ◽  
Pregnancy Outcome ◽  
Immune Cells ◽  
Embryo Implantation ◽  
Substantial Improvement ◽  
Subsequent Pregnancy ◽  
Endometrial Biopsy ◽  
Implantation Failure ◽  
Uterine Receptivity ◽  
Major Barrier

Implantation failure, which is presently the major barrier in human fertility, is attributed, in many cases, to the failure of the uterus to acquire receptivity. The transition into a receptive uterus includes cellular changes in the endometrium and the modulated expression of different cytokines, growth factors, transcription factors, and prostaglandins. These molecules partake in the generation of an inflammatory response followed by the recruitment of immune cells. These cells have shown to be involved in the maternal immune tolerance toward the implanted embryo as well as in the maternal–fetus interaction during pregnancy. Most of the accumulated evidence indicates that embryo implantation is associated with an active Th1 inflammatory response while a Th2-humoral inflammation is required for pregnancy maintenance. Yet, recent findings suggest that a Th1 inflammatory response is also necessary for the acquisition of uterine receptivity. This notion was originally suggested by reports from our and other clinical centers worldwide that IVF patients with repeated implantation failure subjected to endometrial biopsy exhibit a substantial improvement in their chances to conceive. These findings, followed by the demonstration of an elevated pro-inflammatory cytokine/chemokine expression, as well as an increased abundance of immune cells, in the endometrium of these patients, raised the idea that acquisition of uterine receptivity is closely associated with an inflammatory response. This review summarizes the molecular and biochemical evidence that confirm this notion and proposes a mechanism by which injury-induced inflammation improves uterine receptivity and the subsequent pregnancy outcome.

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

2006 ◽  
Vol 2006 ◽  
pp. 1-9 ◽  
Author(s):  
Yogesh Kumar Jaiswal ◽  
Madan Mohan Chaturvedi ◽  
Kaushik Deb
Keyword(s):  
Embryonic Development ◽  
Pregnancy Loss ◽  
Mouse Embryos ◽  
Preimplantation Embryos ◽  
Implantation Failure ◽  
Normal Pattern ◽  
Bacterial Endotoxins ◽  
Mammalian Embryonic Development ◽  
Lps Treatment

Mammalian embryonic development is regulated by several cytokines and growth factors from embryonic or maternal origins. Since CSF-1 plays important role in embryonic development and implantation, we investigated its role in gram-negative bacterial LPS-induced implantation failure. The effect of LPS on normal (nonsuperovulated) and superovulated in vivo-produced embryos was assessed by signs of morphological degeneration. A significantly similar number of morphologically degenerated embryos recovered from both nonsuperovulated and superovulated LPS treated animals on day 2.5 of pregnancy onwards were morphologically and developmentally abnormal as compared to their respective controls (P<.001. Normal CSF-1 expression level and pattern were also altered through the preimplantation period in the mouse embryos and uterine horns after LPS treatment. This deviation from the normal pattern and level of CSF-1 expression in the preimplantation embryos and uterine tissues suggest a role for CSF-1 in LPS-induced implantation failure.

scholarly journals Rapamycin Corrects T Regulatory Cell Depletion and Improves Embryo Implantation and Live Birth Rates in a Murine Model

2019 ◽  
Vol 26 (12) ◽  
pp. 1545-1556 ◽  
Author(s):  
Greene Donald Royster ◽  
Justine C. Harris ◽  
Amanda Nelson ◽  
Yessenia Castro ◽  
R. Patrick Weitzel ◽  
...  
Keyword(s):  
Murine Model ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Embryo Implantation ◽  
Mammalian Target Of Rapamycin ◽  
Unexplained Infertility ◽  
Implantation Failure ◽  
T Regulatory Cell ◽  
Recurrent Implantation Failure ◽  
Regulatory Cell

There are few treatments for patients with recurrent pregnancy loss (RPL) or recurrent implantation failure (RIF). Women with RPL and unexplained infertility have lower T regulatory cell (Treg) expression when compared to fertile controls. A murine model has been developed with depletion of regulatory T cells (DEREG) after administration of diphtheria toxin (DT), resulting in smaller litter sizes, secondary to embryo implantation failure. Numerous murine studies have shown that adoptive transfer of CD4+CD25+FoxP3+ Tregs from donors improves litter sizes in DEREG mice with depleted Tregs. Our hypothesis is that DEREG mice treated with a single dose of DT will deplete Tregs and subsequently decrease litter sizes and that treatment with rapamycin (sirolimus; Pfizer) during the time of embryo implantation will increase Tregs and restore litter sizes nearly back to normal levels. Syngeneic mating of DEREG mice after depletion of Tregs resulted in smaller litter sizes and this defect was reversed when these DEREG mice were treated with rapamycin at the time of embryo implantation. The importance of Tregs at the time of embryo implantation has been well established and immunotherapy treatments, such as rapamycin (mammalian target of rapamycin inhibitor), may prove to be an effective treatment for patients with RPL, RIF, or unexplained infertility with low Treg.

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