IGF2 stimulates fetal growth in a sex- and organ-dependent manner

White, Verónica; Jawerbaum, Alicia; Mazzucco, María Belén; Gauster, Martin; Desoyé, Gernot; Hiden, Ursula

doi:10.1038/pr.2017.221

Cited by 41 publications

(30 citation statements)

References 48 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since previous studies have shown that environmental factors can affect DNA methylation as well as gene expression in a sex-specific manner [ 36 , 37 ], we also explored sex-specific effects. Owing to the small sample size in DNA methylation analysis, we did not explore sex-specific effects on methylation level.…”

Section: Resultsmentioning

confidence: 99%

Early prenatal alcohol exposure alters imprinted gene expression in placenta and embryo in a mouse model

Marjonen¹,

Toivonen²,

Lahti³

et al. 2018

PLoS ONE

View full text Add to dashboard Cite

Prenatal alcohol exposure (PAE) can harm the embryonic development and cause life-long consequences in offspring’s health. To clarify the molecular mechanisms of PAE we have used a mouse model of early alcohol exposure, which is based on maternal ad libitum ingestion of 10% (v/v) ethanol for the first eight days of gestation (GD 0.5–8.5). Owing to the detected postnatal growth-restricted phenotype in the offspring of this mouse model and both prenatal and postnatal growth restriction in alcohol-exposed humans, we focused on imprinted genes Insulin-like growth factor 2 (Igf2), H19, Small Nuclear Ribonucleoprotein Polypeptide N (Snrpn) and Paternally expressed gene 3 (Peg3), which all are known to be involved in embryonic and placental growth and development. We studied the effects of alcohol on DNA methylation level at the Igf2/H19 imprinting control region (ICR), Igf2 differentially methylated region 1, Snrpn ICR and Peg3 ICR in 9.5 embryonic days old (E9.5) embryos and placentas by using MassARRAY EpiTYPER. To determine alcohol-induced alterations globally, we also examined methylation in long interspersed nuclear elements (Line-1) in E9.5 placentas. We did not observe any significant alcohol-induced changes in DNA methylation levels. We explored effects of PAE on gene expression of E9.5 embryos as well as E9.5 and E16.5 placentas by using quantitative PCR. The expression of growth promoter gene Igf2 was decreased in the alcohol-exposed E9.5 and E16.5 placentas. The expression of negative growth controller H19 was significantly increased in the alcohol-exposed E9.5 embryos compared to controls, and conversely, a trend of decreased expression in alcohol-exposed E9.5 and E16.5 placentas were observed. Furthermore, increased Snrpn expression in alcohol-exposed E9.5 embryos was also detected. Our study indicates that albeit no alterations in the DNA methylation levels of studied sequences were detected by EpiTYPER, early PAE can affect the expression of imprinted genes in both developing embryo and placenta.

show abstract

Section: Resultsmentioning

confidence: 99%

Early prenatal alcohol exposure alters imprinted gene expression in placenta and embryo in a mouse model

Marjonen¹,

Toivonen²,

Lahti³

et al. 2018

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…IGF-2 is a multifunctional cell proliferation regulation factor, which plays an important role in cell differentiation, embryo growth and development, and tumor cell proliferation [34,35]. The effect of IGF-2 is mainly mediated by the insulin receptor (IR); type1 IGF receptor (IGF-1R); type2 IGF receptor (IGF-2R) [36].…”

Section: Discussionmentioning

confidence: 99%

Autophagy suppression of trophoblast cells induces pregnancy loss by activating decidual NK cytotoxicity and inhibiting trophoblast invasion

Tan¹

Yang

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: The crosstalk between trophoblast cells and decidual NK cells plays an important role in the establishment and maintenance of normal pregnancy. Recent studies reported that autophagy can induce immune tolerance at the maternal fetal interface, while the mechanism remains unclear. Methods: Autophagy levels in the villi of normal and recurrent spontaneous abortion (RSA) patients were detected by transmission electron microscopy. After co-cultured with trophoblast cells pretreated with 3-MA or rapamycin, NK cells were collected and the expression of killer receptors was detected by flow cytometry (FCM). The invasiveness of trophoblasts was tested by Cell invasion assay. Results: Compared with elective pregnancy termination patients, the level of autophagy in the villi of RSA patients was significantly decreased. Inducing the autophagy level in trophoblast cells with rapamycin could significantly inhibit the cytotoxicity of NK cells in the co-culture system, and supplement of IGF-2 could rectify this effect. Meanwhile, autophagy suppression of trophoblasts reduced the level of Paternally Expressed Gene 10 (PEG10), leading to the impairment of trophoblast cell invasion. In addition, NK cells educated by autophagy-inhibited trophoblasts further decreased the proliferation and invasiveness of trophoblasts. In pregnant mice model, injection with 3-MA promoted the cytotoxicity of uterine NK cells, and increased the embryo absorption rate. Conclusion: Autophagy suppression of trophoblasts increase the cytotoxicity of NK cells and damage the trophoblasts invasion possibly by targeting IGF-2 and PEG10, respectively, which ultimately leads to miscarriage.

show abstract

“…IGF-2 is a multifunctional cell proliferation regulation factor, which plays an important role in cell differentiation, embryo growth and development, and tumor cell proliferation [35,36]. The effect of IGF-2 is mainly mediated by the insulin receptor (IR); type 1 IGF receptor (IGF-1R); type 2 IGF receptor (IGF-2R) [37].…”

Section: Discussionmentioning

confidence: 99%

Autophagy suppression of trophoblast cells induces pregnancy loss by activating decidual NK cytotoxicity and inhibiting trophoblast invasion

Tan¹

Yang1

Wang

et al. 2019

Preprint

View full text Add to dashboard Cite

Background: The crosstalk between trophoblast cells and decidual NK cells plays an important role in the establishment and maintenance of normal pregnancy. Recent studies have reported autophagy can induce immune tolerance at the maternal fetal interface, but the mechanism is largely unclear. Methods: Autophagy levels in the villi of normal and recurrent spontaneous abortion (RSA) patients were detected by transmission electron microscopy. In vivo and in vitro, the expression of killer molecules in NK cells was analyzed by flow cytometry (FCM). And the invasiveness of trophoblasts was tested by Cell invasion assay. Results: Compared with normal abortion patients, the level of autophagy in the villi of RSA patients was significantly decreased. In vitro experiments indicated that co-culture with autophagy suppression of trophoblasts (3-MA-pretreated trophoblasts) increased cytotoxicity of NK cell, which was mediated by the upregulation of insulin-like growth factor-2 (IGF-2). Meanwhile, autophagy suppression of trophoblasts led to a low level of Paternally Expressed Gene 10 (PEG10), leading to impaired cell invasion. In addition, NK cells educated by autophagy-inhibited trophoblasts further decreased the proliferation and invasiveness of trophoblasts. Injection with 3-MA in vivo , the cytotoxicity of uterine NK cells in pregnant mice and the embryo absorption rate were significantly increased. Conclusion: Autophagy suppression of trophoblasts should increase the cytotoxicity of NK cells and damage the trophoblasts invasion possibly by targeting IGF-2 and PEG10, respectively, which ultimately leads to miscarriage.

show abstract

IGF2 stimulates fetal growth in a sex- and organ-dependent manner

Cited by 41 publications

References 48 publications

Early prenatal alcohol exposure alters imprinted gene expression in placenta and embryo in a mouse model

Early prenatal alcohol exposure alters imprinted gene expression in placenta and embryo in a mouse model

Autophagy suppression of trophoblast cells induces pregnancy loss by activating decidual NK cytotoxicity and inhibiting trophoblast invasion

Autophagy suppression of trophoblast cells induces pregnancy loss by activating decidual NK cytotoxicity and inhibiting trophoblast invasion

Contact Info

Product

Resources

About