Cysteine dioxygenase and taurine are essential for embryo implantation by involving in E2-ERα and P4-PR signaling in mouse

Background: Taurine performs multiple physiological functions, and the maintenance of taurine level for most mammals relies on active uptake from diet and endogenous taurine synthesis through its synthesis enzymes, including cysteine dioxygenase (CDO). In addition, uterus tissue and uterus fluid are rich in taurine, and taurine synthesis is regulated by estrogen (E₂) and progesterone (P₄), the key Hormones priming embryo-uterine crosstalk during embryo implantation, but the functional interactions and mechanisms among which are largely unknown. The present study was thus proposed to identify the effects of CDO and taurine on embryo implantation and related mechanisms by using Cdo knockout (KO) and ovariectomy (OVX) mouse models.

Results: The uterine CDO expression was assayed from the first day of plugging (d 1) to d 8 and the results showed that CDO expression level increased from d 1 to d 4, followed by a significant decline on d 5 and persisted to d 8, which was highly correlated with serum and uterine taurine levels, and serum P₄ concentration. Next, Cdo KO mouse was established by CRISPER/Cas9. It was showed that Cdo deletion sharply decreased the taurine levels both in serum and uterus tissue, causing implantation defects and severe subfertility. However, the implantation defects in Cdo KO mice were partly rescued by the taurine supplementation. In addition, Cdo deletion led to a sharp decrease in the expressions of P₄ receptor (PR) and its responsive genes Ihh, Hoxa10 and Hand2. Although the expression of uterine Estrogen Receptor (ERα) had no significant change, the levels of ERα induced genes (Muc1, Ltf) during the implantation window were upregulated after Cdo deletion. These accompanied by the suppression of stroma cell proliferation. Meanwhile, E₂ inhibited CDO expression through ERα and P₄ upregulated CDO expression through PR.

Conclusion: The present study firstly demonstrates that taurine and CDO play prominent roles in uterine receptivity and embryo implantation by involving in E₂-ERα and P₄-PR signaling. These are crucial for our understanding the mechanism of embryo implantation, and infer that taurine is a potential agent for improving reproductive efficiency of livestock industry and reproductive medicine.

CDO; E2; Embryo implantation; P4; Taurine.