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Recently，Associate Professor Wang Xiangguo’s research group at the School of Animal Science and Technology, Beijing Agricultural University published an article in the International Journal of Biological Macromolecules (International Journal of Biological Macromolecules) published online titled "CREG1 targets and binds IGF2R to promote the formation and release of exosomes from bovine placental trophoblast cells and participates in the differentiation regulation of placental organoids accompanied by exosome transport" (CREG1 promotes bovine placental trophoblast cells exosome release by targeting IGF2R and participates in regulating organoid differentiation via exosomes transport)'s research paper.

The placenta is the link between the fetus and mother during pregnancy in mammals。The normal growth and function of the placenta is the key to ensuring a successful pregnancy。Recurrent miscarriage、Fetal growth restriction、Common pregnancy diseases such as preeclampsia are related to defects in early placental development。Trophoblast cells are important component cells of placenta tissue，Establishing effective contact between fetus and mother through differentiation into cell types with different functions。Therefore，Early proliferation and differentiation of placental trophoblast cells are key events in placental formation，And regulated by multiple genes。

Exosomes are an intercellular communication medium secreted bet365 online sports betting liveby placental cells during pregnancy，Its occurrence and release are regulated by a variety of secreted glycoproteins。CREG1 is a secreted glycoprotein widely expressed in various organs and tissues of the body，Has the ability to inhibit cell proliferation、Promotes cell differentiation。IGF2R is a transmembrane multifunctional glycoprotein encoded by the maternal allele，Located on the cell surface，Also involved in regulating cell growth and differentiation。Confirmed by research，CREG1 inhibits the proliferation of human embryonal carcinoma cells by binding to IGF2R。Also，CREG1 is also involved in endocytosis and endosome-lysosome sorting and transport processes。

Cow’s placenta is cotyledonous type placenta，The placental plexus consists of the cotyledons formed by fetal chorioallantoic membrane and amniotic chorion and the uterine caruncle formed by endometrial epithelium。Research team found，During the early development of the placenta of dairy cows，CREG1、IGF2R and exosome marker proteins are mainly expressed in placental trophoblast cells，Expression increases with increasing gestational months。Overexpression of Creg1 gene enhances the occurrence and release of exosomes derived from placental trophoblast cells，Knocking down the expression of Igf2r gene not only inhibits the occurrence of exosomes，Also inhibits the occurrence and release of exosomes induced by Creg1 gene overexpression。Therefore，IGF2R is not only a positive binding protein of CREG1 but can also regulate the expression of CREG1 through feedback regulation。The research team discovered simultaneously，IGF2R can bind to Rab11，In turn, it promotes the formation and release of exosomes from placental trophoblast cells。

Figure 1 CREG1 targets bet365 online sports bettingand binds to IGF2R to regulate the occurrence and release of exosomes

Further research confirmed by the research team，CREG1-rich exosomes added to organoid culture matrix based on primary placental trophoblast cells，To day 15 of bovine placental organoid culture，Organoids derived from bovine primary placental trophoblast cells showed obvious signs of cell differentiation。Discovered by transcriptome analysis，Addition of CREG1-rich exosomes to placental trophoblast organoids changes gene expression patterns in the organoids，Contains endocytosis、PI3K-Akt signaling pathway、Oxidative phosphorylation、Protein breakdown and absorption、Endoplasmic reticulum protein processing、Graft rejection, etc.。

Figure 2 CREG1 regulates the occurrence and release of exosomes to promote the differentiation of bovine placental trophoblast cell-derived organoids

This study preliminarily elucidates the mechanism by which CREG1 regulates the proliferation and differentiation of bovine placental trophoblast cells in early pregnancy，Provides theoretical and practical basis for the diagnosis and treatment of early placental development defects。

Figure 3 CREG1 regulates the generation and release of exosomes to promote the differentiation of bovine placental trophoblast cell-derived organoids

Yuan Naihan, a master’s student at the School of Animal Science and Technology, Beijing Agricultural University、Young teacher Dr. Xiao Longfei is the co-first author of the paper，Associate Professor Wang Xiangguo is the corresponding author of the paper,Professor Sheng Xihui、Associate Professor Qi Xiaolong、Professor Guo Kaijun，Dr. Liu Binying, School of Biology and Resources and Environment，Researcher Yang Xiaowen from Beijing Institute of Animal Husbandry and Veterinary Medicine, Chinese Academy of Agricultural Sciences and others participated in this work。

This research was funded by the National Natural bet365 online sports bettingScience Foundation of China (32273079) and the Science and Technology Innovation Support Program of Beijing Agricultural University (BUA-HHXD2023)。

Paper link:https://www.sciencedirect.com/science/article/abs/pii/S0141813024041035