Retinoic acid synthesis and metabolism are concurrent in the mouse uterus during peri-implantation.
Vitamin A (retinol) and its active metabolite, retinoic acid (RA), serve dual roles in the female reproductive tract. Cytochrome P450 26A1 (Cyp26a1), an RA-metabolizing enzyme, is involved in mammalian early pregnancy. In order to investigate the role of RA synthesis and metabolism during embryo implantation, we first investigated the spatiotemporal expression of RA-signal in the mouse uterus during the peri-implantation period. RA-signal-related molecules, including binding proteins, synthesizing enzymes, catabolizing enzymes and receptors, were all expressed in the mouse uterus during embryo implantation. The locations of the RA synthetic system (Aldh1a1, Aldh1a2, CRBP1) and catabolizing enzyme (Cyp26a1) were distinctive in the mouse uterus during the peri-implantation period. Aldh1a1 was located in the gland epithelium, whereas Aldh1a2 and CRBP1 were located in the stroma and Cyp26a1 was expressed in the luminal and glandular epithelium. These results demonstrate that RA synthesis occurs in the stroma, whereas RA metabolism takes place in the endometrial epithelium. When endometrial epithelial cells were isolated on day 4.5 of pregnancy and treated with E(2) (17beta-estradiol) or a combination of E(2) and progesterone, all-trans-RA (10 μM) significantly down-regulated the expression of LIF, HB-EF and CSF-1 in these cells in vitro. Taken together, these results suggest that the accumulation of RA in the stroma during mouse embryo implantation has an inhibitory effect on the expression of the three implantation-essential genes, LIF, HB-EGF and CSF-1. Therefore, the expression of Cyp26a1 in luminal and glandular epithelium might block the adverse effect of RA in order to promote successful embryo implantation.
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Chaoyang District, Beijing, People's Republic of China. majj@ioz.ac.cn
Jing-jing
JJ
Ma
Bing-chen
BC
Han
Ying
Y
Yang
Jing-pian
JP
Peng
D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D010064:Embryo Implantation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D004717:Endometrium / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D011247:Pregnancy; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis / Q000235:genetics; D050697:Retinal Dehydrogenase; D000072516:Retinoic Acid 4-Hydroxylase; D054840:Retinol-Binding Proteins, Cellular / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology
C581954:CrbpI protein, mouse; D018168:Receptors, Retinoic Acid; D054840:Retinol-Binding Proteins, Cellular; C082928:retinoic acid binding protein II, cellular; C082925:retinoic acid receptor beta; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; C000607080:Cyp26a1 protein, mouse; D000072516:Retinoic Acid 4-Hydroxylase; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C515028:ALDH1A1 protein, mouse; C512722:Aldh1a2 protein, mouse; D050697:Retinal Dehydrogenase