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Retinoic acid synthesis and metabolism are concurrent in the mouse uterus during peri-implantation

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Abstract

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 E2 (17beta-estradiol) or a combination of E2 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.

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Acknowledgments

This work was supported by grants from the National Basic Research Program of China (No. 2011CB944402), the National Natural Science Foundation of China (No. 31171435) and the National Key Technology R&D Program (2012BAI31B07).

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Authors and Affiliations

  1. State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, #1 Beichen West Road, Chaoyang District, Beijing, 100101, People’s Republic of China

    Jing-jing Ma, Bing-chen Han, Ying Yang & Jing-pian Peng

  2. Graduate University of the Chinese Academy of Sciences, 100080, Beijing, China

    Jing-jing Ma

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  1. Jing-jing Ma
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  2. Bing-chen Han
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Correspondence to Jing-pian Peng.

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Ma, Jj., Han, Bc., Yang, Y. et al. Retinoic acid synthesis and metabolism are concurrent in the mouse uterus during peri-implantation. Cell Tissue Res 350, 525–537 (2012). https://doi.org/10.1007/s00441-012-1507-4

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