Identification of 9 uterine genes that are regulated during mouse pregnancy and exhibit abnormal levels in the cyclooxygenase-1 knockout mouse

Zhao, Bo; Koon, Deanna; Curtis, A; Soper, Jessica; Bethin, Kathleen E.

doi:10.1186/1477-7827-5-28

Cited by 8 publications

(5 citation statements)

References 75 publications

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“…Tnfrsf9 expression increases dramatically in the murine uterus during implantation but decreases between days 13 and 19 of gestation (Zhao et al. ; Eckstrum and Bany ). This downregulation may help maintain a successful pregnancy (Sykes et al.…”

Section: Discussionmentioning

confidence: 99%

Maternal age effects on myometrial expression of contractile proteins, uterine gene expression, and contractile activity during labor in the rat

et al. 2015

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Advanced maternal age of first time pregnant mothers is associated with prolonged and dysfunctional labor and significant risk of emergency cesarean section. We investigated the influence of maternal age on myometrial contractility, expression of contractile associated proteins (CAPs), and global gene expression in the parturient uterus. Female Wistar rats either 8 (YOUNG n = 10) or 24 (OLDER n = 10) weeks old were fed laboratory chow, mated, and killed during parturition. Myometrial strips were dissected to determine contractile activity, cholesterol (CHOL) and triglycerides (TAG) content, protein expression of connexin-43 (GJA1), prostaglandin-endoperoxide synthase 2 (PTGS2), and caveolin 1 (CAV-1). Maternal plasma concentrations of prostaglandins PGE2, PGF2α, and progesterone were determined by RIA. Global gene expression in uterine samples was compared using Affymetrix Genechip Gene 2.0 ST arrays and Ingenuity Pathway analysis (IPA). Spontaneous contractility in myometrium exhibited by YOUNG rats was threefold greater than OLDER animals (P < 0.027) but maternal age had no significant effect on myometrial CAP expression, lipid profiles, or pregnancy-related hormones. OLDER myometrium increased contractile activity in response to PGF2α, phenylephrine, and carbachol, a response absent in YOUNG rats (all P < 0.002). Microarray analysis identified that maternal age affected expression of genes related to immune and inflammatory responses, lipid transport and metabolism, steroid metabolism, tissue remodeling, and smooth muscle contraction. In conclusion YOUNG laboring rat myometrium seems primed to contract maximally, whereas activity is blunted in OLDER animals and requires stimulation to meet contractile potential. Further work investigating maternal age effects on myometrial function is required with focus on lipid metabolism and inflammatory pathways.

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Section: Discussionmentioning

confidence: 99%

Maternal age effects on myometrial expression of contractile proteins, uterine gene expression, and contractile activity during labor in the rat

et al. 2015

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“…Recently Zhao, et al showed that Tnfrsf9 mRNA can be detected in the implantation sites of pregnant mice and levels decrease between Days 13.5 and 18 of pregnancy (Zhao, Koon, Curtis, Soper and Bethin, 2007). The present study extends this work and shows that Tnfrsf9 expression dramatically increases in implantation sites of the uterus during the implantation phase of pregnancy.…”

Section: Discussionmentioning

confidence: 99%

“…In that regard, although TNFRSF9 seems to play many roles in the immune system, very little is known about Tnfrsf9 expression at implantation sites in the uteri of pregnant mammals. Recently, Tnfrsf9 expression in the late mouse uterus and placenta was partially characterized (Zhao, et al, 2007). However, to the best of our knowledge, little is known about the expression of this gene in the uterus or conceptus during the implantation phase of early pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Tumor necrosis factor receptor subfamily 9 (Tnfrsf9) gene is expressed in distinct cell populations in mouse uterus and conceptus during implantation period of pregnancy

Eckstrum

Bany

2011

Cell Tissue Res

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Tnfrsf9 gene expression has previously been characterized in the late pregnant mouse uterus and placenta. However, little is known about its expression in the uterus during the implantation phase of early pregnancy. Since TNFRSF9 is known to play a potentially important role in immune function in general, the purpose of this study was to assess the levels and localization of Tnfrsf9 expression in the mouse uterus and conceptus during implantation. Relative Tnfrsf9 mRNA levels were significantly increased in implantation compared to non-implantation site tissue on Days 6.5- 8.5 of pregnancy. This increase did not depend on the presence of the conceptus, as mRNA levels were not significantly different between pregnant implantation sites and artificially-induced deciduomas. Localization using in situ hybridization revealed that a subpopulation of endothelial as well as uterine natural killer cells expressed Tnfrsf9 in the endometrium during implantation. In the developing conceptus, primary trophoblast giant and ectoplacental cells expressed Tnfrsf9 on Days 6.5-8.5. This was followed by expression in the trophoblast giant cell layers surrounding the conceptus on Day 9.5 of pregnancy. Since 2 main splice forms of Tnfrsf9 mRNA exist and encode proteins which have distinct biological functions, we also determined their presence in these tissues. Both mRNA splice forms were present in uterine and conceptus tissues as determined by RT-PCR. In conclusion, both membrane and soluble forms of Tnfrsf9 are expressed in specific cell types of the uterus and conceptus during the progression of implantation in mice and thus may play an important role in this process.

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“…After ovariectomy, these mice delivered normally, suggesting that, in this species, PGF 2␣ was essential for luteolysis but not for the subsequent process of parturition itself. Ablation of PGHS-1 also causes prolonged gestation, suggesting this isoform was responsible for the endometrial synthesis of the luteolytic PGF 2␣ (95,232). Remarkably, when both the PGHS-1 and OT genes were disrupted, parturition began on time (95).…”

Section: Limitations and Benefits Of Currently Favored Animal Modelsmentioning

confidence: 99%

Are animal models relevant to key aspects of human parturition?

Mitchell

Taggart²

2009

American Journal of Physiology-Regulatory, Integrative and Comp

229

233

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Preterm birth remains the most serious complication of pregnancy and is associated with increased rates of infant death or permanent neurodevelopmental disability. Our understanding of the regulation of parturition remains inadequate. The scientific literature, largely derived from rodent animal models, suggests two major mechanisms regulating the timing of parturition: the withdrawal of the steroid hormone progesterone and a proinflammatory response by the immune system. However, available evidence strongly suggests that parturition in the human has significantly different regulators and mediators from those in most of the animal models. Our objectives are to critically review the data and concepts that have arisen from use of animal models for parturition and to rationalize the use of a new model. Many animal models have contributed to advances in our understanding of the regulation of parturition. However, we suggest that those animals dependent on progesterone withdrawal to initiate parturition clearly have a limitation to their translation to the human. In such models, a linear sequence of events (e.g., luteolysis, progesterone withdrawal, uterine activation, parturition) gives rise to the concept of a "trigger" mechanism. Conversely, we propose that human parturition may arise from the concomitant maturation of several systems in parallel. We have termed this novel concept "modular accumulation of physiological systems" (MAPS). We also emphasize the urgency to determine the precise role of the immune system in the process of parturition in situations other than intrauterine infection. Finally, we accentuate the need to develop a nonprimate animal model whose physiology is more relevant to human parturition. We suggest that the guinea pig displays several key physiological characteristics of gestation that more closely resemble human pregnancy than do currently favored animal models. We conclude that the application of novel concepts and new models are required to advance translational research in parturition.

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Identification of 9 uterine genes that are regulated during mouse pregnancy and exhibit abnormal levels in the cyclooxygenase-1 knockout mouse

Cited by 8 publications

References 75 publications

Maternal age effects on myometrial expression of contractile proteins, uterine gene expression, and contractile activity during labor in the rat

Maternal age effects on myometrial expression of contractile proteins, uterine gene expression, and contractile activity during labor in the rat

Tumor necrosis factor receptor subfamily 9 (Tnfrsf9) gene is expressed in distinct cell populations in mouse uterus and conceptus during implantation period of pregnancy

Are animal models relevant to key aspects of human parturition?

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