The uterus is transiently receptive for embryo implantation.It remains to be understood why the uterus does not reject a semi-allogeneic embryo(to the biological mother)or an allogeneic embryo(to a surrogate)for impla...The uterus is transiently receptive for embryo implantation.It remains to be understood why the uterus does not reject a semi-allogeneic embryo(to the biological mother)or an allogeneic embryo(to a surrogate)for implantation.To gain insights,we examined uterine early response genes approaching embryo attachment on day 3 post coitum(D3)at 22 hours when blue dye reaction,an indication of embryo attachment,had not manifested in mice.C57BL/6 pseudo-pregnant(control)and pregnant mouse uteri were collected on D3 at 22 hours for microarray analysis.The self-assembling-manifold(SAM)algorithm identified 21,858 unique probesets.Principal component analysis indicated a clear separation between the pseudo-pregnant and pregnant groups.There were 106 upregulated and five downregulated protein-coding genes in the pregnant uterus with fold change(fc)>1.5 andq value<5%.Gene ontology(GO)analysis of the 106 upregulated genes revealed 38 significant GO biological process(GOBP)terms(P<0.05),and 32(84%)of them were associated with immune responses,with a dominant natural killer(NK)cell activation signature.Among the top eight upregulated protein-coding genes,Cyp26a1 inactivates retinoic acid(RA)whileLrat promotes vitamin A storage,both of which are expected to attenuate RA bioavailability;Atp6v0d2 andGjb2 play roles in ion transport and transmembrane transport;Gzmb,Gzmc,andIl2rb are involved in immune responses;andTdo2 is important for kynurenine pathway.Most of these genes or their related pathways have functions in immune regulations.RA signaling has been implicated in immune tolerance and immune homeostasis,and uterine NK cells have been implicated in immunotolerance at the maternal-fetal interface in the placenta.The mechanisms of immune responses approaching embryo attachment remain to be elucidated.The coordinated effects of the early response genes may hold the keys to the question of why the uterus does not reject an implanting embryo.展开更多
基金This study was supported by the grants of NIH R15HD066301,NIH R01HD065939,and NIH R03 HD100652 to X.Y.
文摘The uterus is transiently receptive for embryo implantation.It remains to be understood why the uterus does not reject a semi-allogeneic embryo(to the biological mother)or an allogeneic embryo(to a surrogate)for implantation.To gain insights,we examined uterine early response genes approaching embryo attachment on day 3 post coitum(D3)at 22 hours when blue dye reaction,an indication of embryo attachment,had not manifested in mice.C57BL/6 pseudo-pregnant(control)and pregnant mouse uteri were collected on D3 at 22 hours for microarray analysis.The self-assembling-manifold(SAM)algorithm identified 21,858 unique probesets.Principal component analysis indicated a clear separation between the pseudo-pregnant and pregnant groups.There were 106 upregulated and five downregulated protein-coding genes in the pregnant uterus with fold change(fc)>1.5 andq value<5%.Gene ontology(GO)analysis of the 106 upregulated genes revealed 38 significant GO biological process(GOBP)terms(P<0.05),and 32(84%)of them were associated with immune responses,with a dominant natural killer(NK)cell activation signature.Among the top eight upregulated protein-coding genes,Cyp26a1 inactivates retinoic acid(RA)whileLrat promotes vitamin A storage,both of which are expected to attenuate RA bioavailability;Atp6v0d2 andGjb2 play roles in ion transport and transmembrane transport;Gzmb,Gzmc,andIl2rb are involved in immune responses;andTdo2 is important for kynurenine pathway.Most of these genes or their related pathways have functions in immune regulations.RA signaling has been implicated in immune tolerance and immune homeostasis,and uterine NK cells have been implicated in immunotolerance at the maternal-fetal interface in the placenta.The mechanisms of immune responses approaching embryo attachment remain to be elucidated.The coordinated effects of the early response genes may hold the keys to the question of why the uterus does not reject an implanting embryo.
