This study aimed to examine the expression of the genes associated with different development stages of primordial germ cells (PGCs) in differentiating mouse embryonic stem cells (mESCs). The cells were cultured in three groups of control, 10-8 M of all-trans retinoic acid and the combination of 10-7 M of Progesterone and retinoic acid for 7, 12, 17, and 22 days. Immunofluorescent and Quantitative RT-PCR were used to evaluate the effect of progesterone on the differentiation of mESCs into primordial germ cells. RA-treated cells exhibited increased expression of Fragilis, Stella, Dazl, Stra8, Sycp3, and Gdf9 genes and decreased expression of Oct4, Mvh genes compared to the non-treated controls. Furthermore, RA in combination with progesterone (RA?P) led to increased expression of Oct4, Fragilis, Stella, Dazl, Sycp3, Gdf9 and decreased expression of Mvh, and Stra8 genes compared to the RA-treated scenario. Immunofluorescence detection of Stella and Mvh showed that the expression levels of the cells treated with RA+P are much higher than those of the other groups. Our project showed that under the influence of the induced factors, mESCs can spontaneously differentiate into germ cells. Also, the combination of RA+P can enhance and accelerate the differentiation of mESCs into germ cells.