IGF-I Overexpression Causes Fetal Loss during Placentation in Mice

Nakamura, Osamu; Hondo, Eiichi; Namba, Yasuharu; Kiso, Yasuo

doi:10.1262/jrd.50.375

Cited by 10 publications

(8 citation statements)

References 21 publications

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“…We reported that dNK cells from patients who underwent spontaneous abortions showed lower miR-483-3p expression, which correlated well with increased IGF-1 production, perforin expression and cytotoxic activity when compared with dNK cells from healthy controls. It has been reported that IGF-1 overexpression can cause fetal loss during placentation in mice; these high levels of IGF-1 could directly alter the characteristics and functions of the uterine NK cells46. Our histological analysis data also show that IGF-1 expression is higher in decidual tissues from patients with spontaneous abortions than in tissues from healthy controls in vivo (Supplementary Fig.…”

Section: Discussionsupporting

confidence: 72%

IGF-1 promotes the development and cytotoxic activity of human NK cells

Sun

et al. 2013

Nat Commun

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Insulin-like growth factor 1 (IGF-1) is a critical regulator of many physiological functions, ranging from longevity to immunity. However, little is known about the role of IGF-1 in natural killer cell development and function. Here, we identify an essential role for IGF-1 in the positive regulation of human natural killer cell development and cytotoxicity. Specifically, we show that human natural killer cells have the ability to produce IGF-1 and that differential endogenous IGF-1 expression leads to disparate cytotoxicity in human primary natural killer cells. Moreover, miR-483-3p is identified as a critical regulator of IGF-1 expression in natural killer cells. Overexpression of miR-483-3p has an effect similar to IGF-1 blockade and decreased natural killer cell cytotoxicity, whereas inhibition of miR-483-3p has the opposite effect, which is reversible with IGF-1 neutralizing antibody. These findings indicate that IGF-1 and miR-483-3p belong to a new class of natural killer cell functional modulators and strengthen the prominent role of IGF-1 in innate immunity.

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Section: Discussionsupporting

confidence: 72%

IGF-1 promotes the development and cytotoxic activity of human NK cells

Sun

et al. 2013

Nat Commun

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“…We suggest that PF-E inhibited the development of preimplantation embryos by impacting the function of embryo-derived factors rather than directly impairing their synthesis and secretion. On the other hand, although growth factors are important for fetal development, their overexpression may also have adverse effects (35). The mechanism involved in this abnormal increase of embryonic growth factors is unclear.…”

Section: Discussionmentioning

confidence: 99%

Attenuated oocyte fertilization and embryo development associated with altered growth factor/signal transduction induced by endometriotic peritoneal fluid

Ding

Chen

Luo

et al. 2010

Fertility and Sterility

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“…Placental morphogenesis accompanied with trophoblast development may be associated with the apoptosis of uNK cells through the regulation of FasL release. I n i n s u l i n -l i k e g r o w t h f a c t o r ( I G F ) -1 overexpressing mice, apoptosis of uNK cells is clearly inhibited, and moreover, fetal loss is frequently occurred following the progress of pregnancy [21]. This report estimated a functional necessity of uNK cells in the normal process of successful pregnancy.…”

Section: Discussionmentioning

confidence: 73%

Involvement of the Fas Ligand and Fas System in Apoptosis Induction of Mouse Uterine Natural Killer Cells

Kusakabe

Otsuki

Kiso

2005

Journal of Reproduction and Development

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Abstract. Uterine natural killer (uNK) cells in the pregnant uterus are known to be associated with the normal development of the placenta. In the mouse pregnant uterus, many uNK cells exist during mid pregnancy, although they show a sudden decrease during late pregnancy and almost disappear before delivery. Our previous study indicated that uNK cells showed clear apoptotic morphology during late pregnancy. Therefore, the present study was carried out to define the involvement of Fas ligand (FasL) and Fas in apoptosis induction of uNK cells. Immunohistochemical analyses revealed that uNK cells expressed FasL in the cytoplasmic granules and Fas on the cell membrane during late pregnancy. In lpr/lpr mice, which genetically lack Fas, many uNK cells were clearly observed during late pregnancy compared with wild-type mice, and moreover uNK cells still existed at day-18 of pregnancy, although there were few in wild-type mice during the same period. In the experiment of in vitro culture, uNK cells derived from wild-type placenta showed chromatin condensation and DNA fragmentation frequently following the anti-Fas antibody treatment, as compared with the control. From these results, it is suggested that FasL and Fas-dependent apoptosis regulates cell appearance of uNK cells in the mouse pregnant uterus. Key words: Apoptosis, Fas, Fas ligand, lpr/lpr mice, Uterine natural killer (uNK) cell (J. Reprod. Dev. 51: [333][334][335][336][337][338][339][340] 2005) he apoptosis induction system that depends on Fas ligand (FasL) and Fas has an essential role in the process of negative selection against the autoreactive T cells [1,2]. MRL-lpr/lpr mice, a model of human systemic lupus erythematosus (SLE) and genetically lacking Fas, show symptoms of autoimmune disease caused by a deficiency of the exclusion system for autoreactive T cells [3]. Endogenous expressions of FasL and Fas were detected in normal mouse uteri and their apoptosis e f f e c t s w e r e s u g g e s t e d t o c o n t r i b u t e t o physiological cell turnover and immune privilege [4]. In human placenta, FasL production from the syncytiotrophoblast is considered to induce apoptosis in maternal aggressive lymphocytes [5].In murine placenta, large granular lymphocytes exist as a major population in the metrial gland and decidua basalis regions [6]. The metrial gland region is formed within the mesometrial triangle after destruction of the circular smooth muscle of the uterine wall, and develops during mid-late pregnancy with the prominent appearance of large granular lymphocytes [6]. The phenotypes of the surface antigens on the large granular lymphocytes are the Ly49G2, NK1.1 and asialo-GM1 that belong on natural killer (NK) cells, and the cytoplasmic granules contain pore forming protein (perforin) and granzyme B [7]. Usually, uterine NK (uNK) cells appear in the decidua basalis of mouse

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IGF-I Overexpression Causes Fetal Loss during Placentation in Mice

Cited by 10 publications

References 21 publications

IGF-1 promotes the development and cytotoxic activity of human NK cells

IGF-1 promotes the development and cytotoxic activity of human NK cells

Attenuated oocyte fertilization and embryo development associated with altered growth factor/signal transduction induced by endometriotic peritoneal fluid

Involvement of the Fas Ligand and Fas System in Apoptosis Induction of Mouse Uterine Natural Killer Cells

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