Fig. 5.

a PGE2 mediates early implantation. a Upon ovulation, PGE2 is secreted by the following reproductive organs: ovaries, endometrium and oviduct, as well as the embryo. EP2 induces LH receptor expression on the corpus luteum to secrete P4 and stimulate its continuous release into the in utero-ovarian circulation. P4 exerts positive feedback to the ovaries, endometrium and oviduct to recognize and maintain the ongoing implantation and embryo development. Via EP4, PGE2 increases the activity of adenylate cyclase (AC) and nitric oxide synthase (OS) successivelyto increase synthesis and nitric oxide (NO) release. NO, a vasodilator, increases the utero-ovarian blood flow and the concentration of pro-pregnancy factors. Additionally, E2 secreted by the embryo and endometrium stimulates PGE2/EP2 to increase the secretion of P4 and inhibits PGFS and CRB1, enzymes involved in the synthesis of PGF2α, an antagonist of PGE2. b In endometrial cells with EP2 receptors, PGE2 stimulates the expression of CXCR4 via the EGFR-PI3K/ERK1/2 pathway. CXCR4 is bound by the chemokine CXCL12, which is secreted by the embryo. PGE2 also stimulates the EGFR-PI3K/ERK1/2 pathway to induce the expression of genes involved in cell proliferation, differentiation and uterine receptivity