Screening and functional verification of potential metabolites for high fertility in sows

Nutritional metabolism greatly influences the embryonic development and pregnancy outcomes. Exploring the metabolic differences between high and low fertility individuals plays pivotal roles in improving reproduction in mammals.

The objective of this study was to explore and confirm the important metabolites influencing the reproductive potential of multiparous sows.

Forty serum samples were collected from Landrace × Large White crossbred sows (3-5 parity) with high litter size (HL) (total litter size ≥ 16) and low litter size (LL) (total litter size ≤ 12) to conduct metabolomics and lipidomics, and differential analysis was applied to screen the potential important metabolite candidates. In addition, porcine trophectoderm cells (PTC) and porcine endometrial stromal cells (PEEC) were used to evaluate the effects of potential metabolite candidates on in vitro embryo adhesion efficiency and the expression of key genes related to trophoblast adhesion and endometrial receptivity.

Through integrated untargeted metabolomics and lipidomics in the serum of sows with different fertility, we identified 37 upregulated metabolites including 3-methylglutaric acid, allantoin, uridine 5'-monophosphate (UMP), asparagine, oxypurinol, oleamide, phosphatidylcholine (PC), and cholesterol ester (ChE) and 77 downregulated metabolites including cholic acid, chenodeoxycholic acid, ursodeoxycholic acid, chenodeoxycholic acid 24-glucuronide (CDCA-24G), triglyceride (TG), phosphatidylethanolamine (PE), and (O-acyl)-ω-hydroxy fatty acid (OAHFA). The altered metabolites were involved in arginine and proline metabolism, purine metabolism, sphingolipid metabolism, ether lipid metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis. In addition, in vitro attachment models revealed that asparagine and PC (18:0_22:6) exhibited higher efficiency (P<0.05) in promoting embryo implantation and the underlying mechanism might involve the enhancement of cellular function related to trophoblast adhesion and endometrial receptivity.

Our results suggest that asparagine and PC (18:0_22:6) may serve as potential key functional metabolites to enhance reproductive capacity. These findings highlight metabolic targets and potential nutritional strategies for improving fertility in mammals.