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The physiological role of mouse b1,4-N-acetylgalactosaminyl transferase in uterus
Dissertation

The physiological role of mouse b1,4-N-acetylgalactosaminyl transferase in uterus

Li, Pei-Tzu
Doctor of Philosophy (PHD), 國立清華大學, 生物資訊與結構生物研究所
2011

Abstract

子宮 助孕酮 胚胎著床 囊胚 b1,4-N-acetylgalactosaminyl transferase B4galnt2 progesterone blastocyst implantation
Glycosylation is a fundamentally important modification in reproductive physiology, including embryo implantation. The B4galnt2 encodes an enzyme, the Sda β-1,4-N-acetylgalactosaminyltransferase II (β4GalNAcT-II, B4galnt2), which catalyzes the GalNAc linking to the Gal of the NeuAcα2-3Galβ terminal structure via the β-1,4 linkage and forms the sda antigen. In the reproductive system, sda antigen has been found in association with glycoproteins, which are specifically related with pregnancy, such as bovine pregnancy-associated glycoproteins (PAGs), zona pellucida glycoprotein 3 (Zp-3) and glycodelin (Gd). Via hormone treatment in vitro and promoter reporter assay, this study realized that B4galnt2 was positively regulated by progesterone (P4) and negatively regulated by estrogen (E2) in the uteri. These results coincided with in vivo observation. During pregnancy, B4galnt2 is significantly expressed on the intracellular portion of uterine tissue for high levels of P4 at E3.5 and E10.5. This study suggested that the uteri could provide Sda modified protein(s) or lipid(s) on the surface of uterine epithelia at these moments. Using siRNA assay to reduce the B4galnt2 expression in vivo, the reduction of embryonic numbers in uteri revealed the importance of this gene in embryo implantation and development. Furthermore, Bgalnt2 was found to locate on the surface and intracellular portion of E3.5 blastocysts, via confocal microscopy observation. The suppression of blastocyst adhesion by the anti-B4galnt2 antibody and lectin, Dolichos biflous agglutinin (DBA), in vitro and in vivo, was demonstrated by the involvement of B4galnt2 in embryonic early implantation. These results suggested that B4galnt2 on the blastocyst membrane surface may be associated with the sda antigen containing protein(s) or lipid(s) on the uterine epithelium. In addition, the sda antigen on the blastocyst membrane surface bound the receptor/acceptor on the endometrial surface to permit early embryo implantation jointly.

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