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Papers by Jennifer Herington

PloS one, 2015

Excessive cytokine inflammatory response due to chronic or superphysiological level of microbial ... more Excessive cytokine inflammatory response due to chronic or superphysiological level of microbial infection during pregnancy leads to pregnancy complications such as early pregnancy defects/loss and preterm birth. Bacterial toxin lipopolysaccharide (LPS), long recognized as a potent proinflammatory mediator, has been identified as a risk factor for pregnancy complications. Alkaline phosphatase (AP) isozymes have been shown to detoxify LPS by dephosphorylation. In this study, we examined the role of alkaline phosphatase (AP) in mitigating LPS-induced early pregnancy complications in mice. We found that 1) the uterus prior to implantation and implantation sites following embryo implantation produce LPS recognition and dephosphorylation molecules TLR4 and tissue non-specific AP (TNAP) isozyme, respectively; 2) uterine TNAP isozyme dephosphorylates LPS at its sites of production; 3) while LPS administration following embryo implantation elicits proinflammatory cytokine mRNA levels at the...

Reproduction (Cambridge, England), 2014

The mouse model has greatly contributed to understanding molecular mechanisms involved in the reg... more The mouse model has greatly contributed to understanding molecular mechanisms involved in the regulation of progesterone (P4) plus estrogen (E)-dependent blastocyst implantation process. However, little is known about contributory molecular mechanisms of the P4-only-dependent blastocyst implantation process that occurs in species such as hamsters, guineapigs, rabbits, pigs, rhesus monkeys, and perhaps humans. We used the hamster as a model of P4-only-dependent blastocyst implantation and carried out cross-species microarray (CSM) analyses to reveal differentially expressed genes at the blastocyst implantation site (BIS), in order to advance the understanding of molecular mechanisms of implantation. Upregulation of 112 genes and downregulation of 77 genes at the BIS were identified using a mouse microarray platform, while use of the human microarray revealed 62 up- and 38 down-regulated genes at the BIS. Excitingly, a sizable number of genes (30 up- and 11 down-regulated genes) were ...

Reproduction, 2007

Within the mouse endometrium, secreted phosphoprotein 1 gene expression is mainly expressed in th... more Within the mouse endometrium, secreted phosphoprotein 1 gene expression is mainly expressed in the luminal epithelium and some macrophages around the onset of implantation. However, during the progression of decidualization it is expressed mainly in the mesometrial decidua. To date, the precise cell types responsible for the expression in the mesometrial decidua has not been absolutely identified. The goal of the present study was to assess the expression of secreted phosphoprotein 1 in uteri of pregnant mice (decidua) during the progression of decidualization and compared it to those undergoing artificially-induced decidualization (deciduoma). Significantly (P< 0.05) greater steadystate levels of secreted phosphoprotein 1 mRNA were seen in the decidua compared to deciduoma. Further, in the decidua, the majority of the secreted phosphoprotein 1 protein (SPP1) was localized within a subpopulation of granulated uterine natural killer (uNK) cells but not co-localized to their granules. However, in addition to being localized to uNK cells, SPP1 protein was also detected in another cell type(s) that were not EGF-like containing mucin-like hormone receptor-like sequence 1 protein (EMR1)-positive immune cells which are known to be present in the uterus at this time. Finally, decidual SPP1 expression dramatically decreased in uteri of interleukin-15-deficient mice which lack uNK cells. In conclusion, SPP1 expression is greater in the mouse decidua compared to the deciduoma after the onset of implantation during the progression of decidualization. Finally, uNK cells were found to be the major source of SPP1 in the pregnant uterus during decidualization. SPP1 might play a key role in uNK killer cell functions in the uterus during decidualization.

Journal of Reproductive Immunology, 2006

Journal of Histochemistry and Cytochemistry, 2007

Journal of Experimental Zoology Part B: Molecular and Developmental Evolution, 2009

A critical period in establishing pregnancy occurs after the onset of implantation but before pla... more A critical period in establishing pregnancy occurs after the onset of implantation but before placental development. Evidence strongly suggests that abnormalities occurring during this period can result in pregnancy termination or in pre-eclampsia; the latter may lead to small-for-gestational-weight offspring that are likely to be unhealthy. Clearly, events occurring in the endometrium during the implantation process are crucial for proper fetal development and for optimal offspring health. In several mammalian species bi-directional communication between the conceptus and endometrium during implantation is required for successful pregnancy. Although different implantation and placentation modes occur in different mammalian species, common aspects of this bi-directional signaling may exist. The molecular signals from the trophoblast cells of the conceptus, which direct endometrial changes during implantation progression, are well known in some non-rodent species. Currently, we know little about such signaling in rodents during implantation progression, when the endometrium undergoes decidualization. This review focuses on data that support the hypothesis that paracrine signals from the rodent conceptus influence decidualization. Where possible, these findings are compared and contrasted to information currently known in other species that exhibit different implantation modes. 3Send correspondence to:

Fertility and Sterility, 2011

Objective-To examine the impact of a recent surgery on development of endometriosis-related adhes... more Objective-To examine the impact of a recent surgery on development of endometriosis-related adhesions in a chimeric model and to determine the therapeutic efficacy of pioglitazone (PIO).

Endocrinology, 2009

The purpose of this study was to determine whether the conceptus directs the formation of a tight... more The purpose of this study was to determine whether the conceptus directs the formation of a tight- and adherens-dependent permeability barrier formed by the primary decidual zone and normal progression of decidual cell differentiation during embryo implantation. Four artificial models of decidualization were used, some apparently more physiological than others. The results show that both the formation of the permeability barrier and decidual cell differentiation of three of the artificial models were quite different from that of pregnant uteri. One artificial model of decidualization, namely pseudopregnant animals receiving concanavalin A-coated Sepharose bead transfers on d 2.5 of pseudopregnancy, better recapitulated the decidual changes that occur in the pregnant uterus undergoing decidualization. This included the formation of a primary decidual zone-like permeability barrier and decidual growth. This model also exhibited similar temporal changes of the expression of genes involved in decidualization that are markers of decidual cell differentiation. Overall, the results of this study indicate that some models of inducing decidualization artificially produce responses that are more similar to those occurring in the pregnant uterus, whereas others are quite different. More importantly, the results suggest that concanavalin A-coated Sepharose beads can provide an equivalent stimulus as the trophectoderm to cause the formation of the primary decidual zone permeability barrier.

Biology of Reproduction, 2007

Uterine natural killer (uNK) cells are the most abundant lymphocyte in the uterus during early pr... more Uterine natural killer (uNK) cells are the most abundant lymphocyte in the uterus during early pregnancy that plays a role in spiral arteriole modifications. In this study, we determined if uNK cell populations differed between mouse decidua and deciduoma. Histochemical staining using Dolichos biflorous agglutinin (DBA) lectin was used to identify uNK cells and classify their stage of maturation. We found a difference in the pattern of localization and density of uNK cells between the decidua and deciduoma at Days 2-4 after the onset of decidualization. Cells were more distributed and the densities were significantly greater in the mesometrial region of the decidua compared to that of the deciduoma. Using double labeling for both DBA lectin binding and bromodeoxyuridine incorporation, we found that the greater number of uNK cells in the decidua were not due to an increase in uNK cell proliferation. Western blot analyses revealed that the increase in uNK cell number was accompanied by a significant increase in both the levels of interferon-gamma (IFNG) and pro-interleukin-18 when a conceptus was present. Vascular morphometry revealed that modifications of the spiral arterioles occurred in the mesometrial decidua but not the deciduoma, which could be attributed to the differences observed in uNK cell number and IFNG production. The present study demonstrates that differences exist in uNK cell populations between decidua and deciduoma, providing evidence that the conceptus provides signals which regulate uNK cell number and function in the uterus during implantation.