Epidermal growth factor represses differentiation of mouse trophoblast stem cells into spongiotrophoblast cells via epidermal growth factor receptor

Nishitani, Kenta; Hayakawa, Koji; Tanaka, Satoshi

doi:10.1016/j.bbrc.2023.03.059

Cited by 3 publications

(1 citation statement)

References 45 publications

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“…29 Upregulation of these genes has recently been associated with the transcriptional promotion of cell proliferation and differentiation by inducing signals for MAPK and PI3K-Akt activation. 30 Studies have previously demonstrated that iron deficiency inhibited PI3K-Akt signaling, while iron supplementation stimulated cell proliferation by activating PI3K/Akt signaling in different cells. 31,32 Iron supplementation increased Akt phosphorylation, while administration of the PI3K inhibitor completely blocked the iron-induced phosphorylation of Akt.…”

Section: Discussionmentioning

confidence: 99%

Ferrous–sucrose complex supplementation regulates maternal plasma metabolism and the fecal microbiota composition and improves neonatal immunity and placental glucose transportation by activating the EGF/PI3K/AKT signaling pathways in sows

Dong,

Liu,

Wan

et al. 2024

Food Funct.

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Section: Discussionmentioning

confidence: 99%

Ferrous–sucrose complex supplementation regulates maternal plasma metabolism and the fecal microbiota composition and improves neonatal immunity and placental glucose transportation by activating the EGF/PI3K/AKT signaling pathways in sows

Dong,

Liu,

Wan

et al. 2024

Food Funct.

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Exploring the molecular underpinnings of macrosomia in gestational diabetes mellitus: The role of EGFR signaling and placental syncytiotrophoblast

Xu,

Sun,

Zheng

et al. 2024

Life Sciences

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Sperm-carried IGF2: towards the discovery of a spark contributing to embryo growth and development

Cannarella,

Rando,

Condorelli

et al. 2024

Molecular Human Reproduction

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Spermatozoa have been shown to carry key RNAs which, according to animal evidence, seem to play a role in early embryo development. In this context, a potential key growth regulator is insulin-like growth factor 2 (IGF2), a highly conserved paternally expressed imprinted gene involved in cell growth and proliferation which, recent observations indicate, is expressed in human spermatozoa. We herein hypothesized that sperm IGF2 gene expression and transmission at fertilization is required to support early embryo development. To test this hypothesis, we analyzed sperm IGF2 mRNA levels in the same semen aliquot used for homologous assisted reproductive technique (ART) in infertile couples and correlated these levels with embryo morphokinetics. To find a mechanistic explanation for the observed results, the transcriptomes of blastocysts obtained after injection of Igf2 mRNA in mouse parthenotes were analyzed. Sperm IGF2 mRNA negatively correlated with time of 2-cell stage (t2), t3, t4, t5, and time of expanded blastocyst (tEB), independently of maternal age, body mass index, anti-Müllerian hormone levels and oocyte quality. An IGF2 mRNA index >4.9 predicted the ability of the embryos to reach the blastocyst stage on day 5, with a sensitivity of 100% and a specificity of 71.6% (AUC 0.845; p < 0.001). In the animal study, transcriptome analysis demonstrated that 65 and 36 genes were, respectively, up- and down-regulated in the experimental group compared to the control group. These genes belong to pathways that regulate early embryo development, thus supporting the findings found in humans. This study has the potential to challenge the longstanding tenet that spermatozoa are simply vehicles carrying paternal DNA. Instead, it suggests that IGF2 mRNA in healthy spermatozoa provides critical support for early embryo development. Pre-ART sperm-carried IGF2 mRNA levels may be used as a marker to predict the chances of obtaining blastocysts to be transferred for infertile couples undergoing ART.

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Epidermal growth factor represses differentiation of mouse trophoblast stem cells into spongiotrophoblast cells via epidermal growth factor receptor

Cited by 3 publications

References 45 publications

Ferrous–sucrose complex supplementation regulates maternal plasma metabolism and the fecal microbiota composition and improves neonatal immunity and placental glucose transportation by activating the EGF/PI3K/AKT signaling pathways in sows

Ferrous–sucrose complex supplementation regulates maternal plasma metabolism and the fecal microbiota composition and improves neonatal immunity and placental glucose transportation by activating the EGF/PI3K/AKT signaling pathways in sows

Exploring the molecular underpinnings of macrosomia in gestational diabetes mellitus: The role of EGFR signaling and placental syncytiotrophoblast

Sperm-carried IGF2: towards the discovery of a spark contributing to embryo growth and development

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