Morphological differentiation of uterine glands in mammals is a postnatal event vulnerable to adverse effects of endocrine disruptors. Exposure of ewe lambs to a progestin from birth to postnatal day 56 prevents development of uterine glands and, as adults, the ewes are unable to exhibit estrous cycles or maintain pregnancy. Uterine epithelia secrete proteins and transport nutrients into the uterine lumen necessary for conceptus development, pregnancy recognition signaling and implantation, including arginine and secreted phosphoprotein 1 (SPP1). Arginine can be metabolized to nitric oxide and to polyamines or act directly to activate MTOR cell signaling to stimulate proliferation, migration, and mRNA translation in trophectoderm cells. SPP1 binds αvβ3 and α5β1 integrins and induces focal adhesion assembly, adhesion and migration of conceptus trophectoderm cells during implantation. Thus, arginine and SPP1 mediate growth, migration, cytoskeletal remodeling and adhesion of trophectoderm essential for pregnancy recognition signaling and implantation.
Bibliographical noteFunding Information:
Supported by USDA CSREES National Research Initiative Grant 2006-35203-17283, National Research Initiative Competitive Grant No. 2006-35203-17283 from the USDA National Institute of Food and Agriculture , and the World Class University (WCU) program (R31–10056) through the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology .
- Amino acids
- Endocrine disruptor
- Secreted phosphoprotein 1
ASJC Scopus subject areas
- Molecular Biology