title: Cyclic adenosine monophosphate-induced argininosuccinate synthase 1 expression is essential during mouse decidualization.
abstract: L-Arginine (L-Arg), a conditional essential amino acid in adults, has been shown to enhance pregnancy outcome. Argininosuccinate synthase (Ass1) and argininosuccinate lyase (Asl) are the key enzyme for L-Arginine (L-Arg) biosynthesis. Based our microarray analysis, Ass1 expression is upregulated significantly at implantation site on day 5 of pregnancy compared to that at inter-implantation site. However, the expression, regulation and function of Ass1 during early pregnancy remain unknown. Here we found that Ass1 is highly expressed in mouse decidua and uterine stromal cells undergoing decidualization, and Asl is weakly expressed in mouse decidua and uterine stromal cells undergoing decidualization. α-Methyl-DL-aspartic acid (MDLA), a specific inhibitor for Ass1, can significantly increase the rate of embryonic reabsorption. Under in vitro induced decidualization, MDLA clearly inhibits the expression of decidual/trophoblast prolactin-related protein (Dtprp), a marker for decidualization in mice. Only Ass1 expression is induced by cAMP through PKA/p-Creb signaling pathway. Results from our cell culture models further indicates that the high level of L-Arg enhances stromal proliferation, while enzymatic activity or Ass1 expression level is essential to determine the magnitude of both mouse and human decidualization. Interestingly, L-Arg at high concentration down-regulates Ass1 and Asl expression by negative feedback to maintain L-Arg homeostasis. These findings highlight that cAMP-induced Ass1 expression is important in controlling the magnitude of decidualization through regulating L-Arg level.
authors.affiliation: School of Life Science, Xiamen University, Xiamen 361005, China; College of Life Science, Anqing Normal University, Anqing 246011, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Huang
authors.affiliation: School of Science, Shantou University, Shantou 515000, China.
authors.forename: Tong-Song
authors.initials: TS
authors.lastname: Wang
authors.affiliation: School of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Yue-Chao
authors.initials: YC
authors.lastname: Zhao
authors.affiliation: School of Life Science, Xiamen University, Xiamen 361005, China.
authors.forename: Ru-Juan
authors.initials: RJ
authors.lastname: Zuo
authors.affiliation: School of Life Science, Xiamen University, Xiamen 361005, China.
authors.forename: Wen-Bo
authors.initials: WB
authors.lastname: Deng
authors.affiliation: School of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Chi
authors.affiliation: School of Science, Shantou University, Shantou 515000, China; College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China. Electronic address: zmyang@scau.edu.cn.
authors.forename: Zeng-Ming
authors.initials: ZM
authors.lastname: Yang
mesh_terms: D000818:Animals; D001120:Arginine / Q000502:physiology; D001123:Argininosuccinate Lyase / Q000235:genetics / Q000378:metabolism; D001124:Argininosuccinate Synthase / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003656:Decidua / Q000201:enzymology* / Q000502:physiology; D010064:Embryo Implantation; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D011247:Pregnancy
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D001120:Arginine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D001123:Argininosuccinate Lyase; D001124:Argininosuccinate Synthase
keywords: Argininosuccinate synthase 1; Decidualization; Uterus; cAMP