Progesterone production is affected by unfolded protein response (UPR) signaling during the luteal phase in mice

Park, Hyo-Jin; Park, Sun-Ji; Koo, Deog‐Bon; Lee, Sang-Rae; Kong, Il‐Keun; Ryoo, Jaewoong; Park, Young‐Il; Chang, Kyu‐Tae; Lee, Dong‐Seok

doi:10.1016/j.lfs.2014.07.033

Cited by 37 publications

(39 citation statements)

References 30 publications

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“…Trophoblasts are cellular targets where Brucella efficiently replicates in association with the ER. Recent studies have confirmed that ER stress is closely related to placental functions, such as placental development, fetal growth restriction (Yang et al, 2015 ), progesterone secretion, and steroidogenic enzyme expression (Park et al, 2014 ). Altering the features of placental trophoblast cells will result in a variety of complications during pregnancy.…”

Section: Introductionmentioning

confidence: 93%

Brucella suis Vaccine Strain 2 Induces Endoplasmic Reticulum Stress that Affects Intracellular Replication in Goat Trophoblast Cells In vitro

Wang

Lin

et al. 2016

Front. Cell. Infect. Microbiol.

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Brucella has been reported to impair placental trophoblasts, a cellular target where Brucella efficiently replicates in association with the endoplasmic reticulum (ER), and ultimately trigger abortion in pregnant animals. However, the precise effects of Brucella on trophoblast cells remain unclear. Here, we describe the infection and replication of Brucella suis vaccine strain 2 (B.suis.S2) in goat trophoblast cells (GTCs) and the cellular and molecular responses induced in vitro. Our studies demonstrated that B.suis.S2 was able to infect and proliferate to high titers, hamper the proliferation of GTCs and induce apoptosis due to ER stress. Tunicamycin (Tm), a pharmacological chaperone that strongly mounts ER stress-induced apoptosis, inhibited B.suis.S2 replication in GTCs. In addition, 4 phenyl butyric acid (4-PBA), a pharmacological chaperone that alleviates ER stress-induced apoptosis, significantly enhanced B.suis.S2 replication in GTCs. The Unfolded Protein Response (UPR) chaperone molecule GRP78 also promoted B.suis.S2 proliferation in GTCs by inhibiting ER stress-induced apoptosis. We also discovered that the IRE1 pathway, but not the PERK or ATF6 pathway, was activated in the process. However, decreasing the expression of phosphoIRE1α and IRE1α proteins with Irestatin 9389 (IRE1 antagonist) in GTCs did not affect the proliferation of B.suis.S2. Although GTC implantation was not affected upon B.suis.S2 infection, progesterone secretion was suppressed, and prolactin and estrogen secretion increased; these effects were accompanied by changes in the expression of genes encoding key steroidogenic enzymes. This study systematically explored the mechanisms of abortion in Brucella infection from the viewpoint of pathogen invasion, ER stress and reproductive endocrinology. Our findings may provide new insight for understanding the mechanisms involved in goat abortions caused by Brucella infection.

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Section: Introductionmentioning

confidence: 93%

Brucella suis Vaccine Strain 2 Induces Endoplasmic Reticulum Stress that Affects Intracellular Replication in Goat Trophoblast Cells In vitro

Wang

Lin

et al. 2016

Front. Cell. Infect. Microbiol.

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“…All three UPR signaling pathways, including adaptive or apoptotic signaling molecules (Grp78, p-eIF2α, ATF4, CHOP, ATF6, p-IRE1α, XBP1 s and p-JNK), are activated during luteal-phase progression during the estrous cycle of bovines] (Park et al, 2013a) and mice (Park et al, 2014). Pro-apoptotic signaling molecules such as cleaved caspase3, JNK, and CHOP were detected, and JNK activation and CHOP expression via ER stress–mediated pro-apoptotic signaling cascades occurred prior to caspase3 activation during the regression stage of the corpus luteum (Urano et al, 2000; McCullough et al, 2001; Novoa et al, 2001; Marciniak et al, 2004; Yamaguchi and Wang 2004; Woo et al, 2009; Park et al, 2013a; Park et al, 2014). Furthermore, the dynamic change of these molecules seems to have some connection with the steroidogenic enzymes, which suggests that the UPR may influence the expression of steroidogenic enzymes (Park et al, 2013a; Park et al, 2013b).…”

Section: Activation Of the Upr In The Ovarian Cyclementioning

confidence: 99%

Dual role for the unfolded protein response in the ovary: adaption and apoptosis

Qiao

2016

Protein &Amp; Cell

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The endoplasmic reticulum (ER) is the principal organelle responsible for several specific cellular functions including synthesis and folding of secretory or membrane proteins, lipid metabolism, and Ca2+ storage. Different physiological as well as pathological stress conditions can, however, perturb ER homeostasis, giving rise to an accumulation of unfolded or misfolded proteins in the ER lumen, a condition termed ER stress. To deal with an increased folding demand, cells activate the unfolded protein response (UPR), which is initially protective but can become detrimental if ER stress is severe and prolonged. Accumulating evidence demonstrates a link between the UPR and ovarian development and function, including follicular growth and maturation, follicular atresia, and corpus luteum biogenesis. Additionally, ER stress and the UPR may also play an important role in the ovary under pathological conditions. Understanding the molecular mechanisms related to the dual role of unfolded protein response in the ovarian physiology and pathology may reveal the pathogenesis of some reproductive endocrine diseases and provide a new guidance to improve the assisted reproductive technology. Here we review the current literature and discuss concepts and progress in understanding the UPR, and we also analyze the role of ER stress and the UPR in the ovary.

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“…During the CL regression stage, increased expression of pJNK and CHOP, two components of ERS-mediated apoptotic cascades, occurs before the increased levels of cleaved caspase-3 are observed (Park et al 2013). These results are further supported by Park's data showing that the ERS and UPR are involved in the mouse CL lifespan, and that the secretion of P 4 is affected by the UPR (Park et al 2014). …”

Section: Involvement Of Ers Response In Corpus Luteum Development Andmentioning

confidence: 52%

The roles of endoplasmic reticulum stress response in female mammalian reproduction

et al. 2015

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Endoplasmic reticulum stress (ERS) activates a protective pathway, called the unfold protein response, for maintaining cellular homeostasis, but cellular apoptosis is triggered by excessive or persistent ERS. Several recent studies imply that the ERS response might have broader physiological roles in the various reproductive processes of female mammals, including embryo implantation, decidualization, preimplantation embryonic development, follicle atresia, and the development of the placenta. This review summarizes the existing data concerning the molecular and biological roles of the ERS response. The study of the functions of the ERS response in mammalian reproduction might provide novel insights into and an understanding of reproductive cell survival and apoptosis under physiological and pathological conditions. The ERS response is a novel signaling pathway for reproductive cell survival and apoptosis. Infertility might be a result of disturbing the ERS response during the process of female reproduction.

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Progesterone production is affected by unfolded protein response (UPR) signaling during the luteal phase in mice

Cited by 37 publications

References 30 publications

Brucella suis Vaccine Strain 2 Induces Endoplasmic Reticulum Stress that Affects Intracellular Replication in Goat Trophoblast Cells In vitro

Brucella suis Vaccine Strain 2 Induces Endoplasmic Reticulum Stress that Affects Intracellular Replication in Goat Trophoblast Cells In vitro

Dual role for the unfolded protein response in the ovary: adaption and apoptosis

The roles of endoplasmic reticulum stress response in female mammalian reproduction

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