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Fatty-Acid Amide Hydrolase Is Expressed in the Mouse Uterus and Embryo during the Periimplantation Period¹

^a Department of Molecular and Integrative Physiology, Ralph L. Smith Research Center, University of Kansas Medical Center, Kansas City, Kansas 66160-7338

Arachidonoylethanolamide (anandamide) is an endogenous ligand for cannabinoid receptors. We demonstrated previously that the periimplantation mouse uterus has high levels of anandamide and can synthesize and hydrolyse anandamide. In the present investigation, we examined the expression of the recently identified fatty-acid amide hydrolase (FAAH) gene, which is involved in hydrolyzing anandamide to arachidonic acid and ethanolamine, in the periimplantation mouse embryo and uterus. As previously reported, Northern blot hybridization detected a transcript of ~2.5 kilobases of FAAH mRNA in whole uterine poly(A)⁺ RNA samples. The levels of this mRNA were higher in the liver and brain than in the uterus. In the uterus, higher accumulation of FAAH mRNA occurred on Days 1–4 followed by declines on later days (Days 5–8) of pregnancy. In situ hybridization detected this mRNA primarily in uterine luminal and glandular epithelial cells on Days 1–4 of pregnancy. With the progression of implantation (Days 5–8), accumulation of this mRNA was retained in the luminal and glandular epithelia. In addition, implanting blastocysts showed accumulation of this mRNA. FAAH mRNA accumulation was absent or minimal in the myometrium during this period. Western blotting detected an ~60-kDa protein in uterine membrane preparations. In preimplantation embryos, FAAH mRNA was present in one-cell and two-cell embryos but was absent in embryos at the eight-cell/morula stage. However, this mRNA was again detected in Day 4 blastocysts. The presence of FAAH mRNA in one- and two-cell embryos reflects accumulation of maternal message, while its presence in blastocysts reflects embryonic gene activation. Collectively, our present and previous results provide evidence that FAAH is expressed in the mouse uterus and embryo during early pregnancy to modulate local levels of anandamide that could be important for embryo development and implantation.

¹ This research was supported in part by grants from the National Institute on Drug Abuse (DA 06668). A center grant in Reproductive Biology (HD 33994) and a center grant in Mental Retardation and Developmental Disabilities (HD 02528) provided access to various core facilities.

² Correspondence: S.K. Dey, Department of Molecular and Integrative Physiology, MRRC 37/3017, University of Kansas Medical Center, Kansas City, KS 66160–7338. FAX: 913 588 5677; sdey{at}kumc.edu

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