The Expression,Regulation And Function Of Fatty Acid Desaturase 3 In Mouse Uterus During Early Pregnancy

Decidualization is required for the successful establishment of pregnancy in mammals.Impaired decidualization can lead to adverse outcomes,for example implantation failure and miscarriage.Fatty acid desaturase 3(Fads3)belongs to the fatty acid desaturase family,which are crucial enzymes for highly unsaturated fatty acid(HUFA)biosynthesis.Based on the high homology with Fads1 and Fads2,Fads3 was also considered as an important enzyme for the biosynthesis of HUFA.Moreover,the expression,regulation and function of Fads3 during early pregnancy in mice are still unclear.In this study,Real-time RT-PCR,in situ hybridization,short interfering RNAs(si-RNAs)were used to determine the expression,regulation and function of Fads3 during mouse uterine decidualization and the effect of different concentrations of docosahexaenoic acid(DHA),linoleic acid(LA)and arachidonic acid(AA)on Fads3.From days 1-4 of pregnancy,there are no Fads1 and Fads2 signals in the uteri.However,Fads1 and Fads2 are weakly expressed in the decidua on days 5-8 of pregnancy.Fads3 signals are undetectable in the uteri from days 1-4 of pregnancy.However,on day 5 of pregnancy,Fads3 signals are detected in the stromal cells surrounding the implanting blastocyst,but no seen in the inter-implantation.Further,Fads3 signals are strongly expressed in the decidua on days 5-8 of pregnancy.On day5 of pseudopregnancy,there are no visible Fads3 signals in the uteri.Fads3 signals are undetectable in the delayed uteri,but significantly expressed in the activated implantation uteri.Under artificial decidualization,Fads3 is highly expressed in decidua.However,there are no visible Fads3 signals in the uninjected uteri horn.Estrogen strongly induces Fads3 m RNA expression in ovariectomized mice.However,in ovariectomized Esr1 KO mice,estrogen has no effect on Fads3 m RNA expression,indicating that estrogen via ER? regulates the expression of Fads3 m RNA.When ovariectomized mice are treated with progesterone,Fads3 expression is significantly increased by progesterone.Fads3 m RNA is significantly increased after stromal cells are treated with progesterone,which is abrogated by RU486 treatment,suggesting progesterone regulation on Fads3 expression is PR-dependent.Fads3 knockdown significantly inhibits Dtprp m RNA level under in vitro decidualization.These results indicate Fads3 may play vital role during decidualization.There was no significant effect on the expression of Fads3 m RNA after stromal cells are treated with 0.4 ?M,2 ?M and 10 ?M of DHA.However,Dtprp m RNA increases up to 2-fold by 10 ?M DHA.The expression of Dtprp and Fads3 m RNA remains unchanged under in vitro decidualization after stromal cells are treated with different concentrations of DHA.When stromal cells are treated with different concentrations of LA,there are no effects on the expression of Dtprp and Fads3 m RNA.However,10 ?M LA inhibits both of Dtprp and Fads3 m RNA levels under in vitro decidualization.Different concentrations of AA don't induce the expression of Fads3 and Dtprp m RNA in the stromal cells.In summary,Fads3 is strongly expressed in the decidual cells and regulated by both of progesterone and estrogen.Knockdown of Fads3 can inhibit decidualization.Fads3 may play a role during mouse decidualization.