The seminal plasma metabolome of high- and low-fertility bulls and the corresponding endometrial metabolome after intra-uterine deposition

The relationship of the seminal plasma (SP) metabolome to the corresponding uterine endometrium metabolome after intra-uterine deposition was studied in Nellore ( Bos indicus ) cattle. The SP metabolome was characterized in bulls classified as high fertility (HF: 56.2 ± 1.8% P/AI; n = 4) or low fertility (LF: 47.0 ± 1.9% P/AI; n = 4) based on 4,002 fixed-time artificial inseminations (AI). Cows underwent synchronization of the stage of the estrous cycle and pooled SP (diluted 1:25 in PBS) from HF (n = 28 cows) and LF (n = 28) bulls was deposited in the body of the uterus at the time of normal AI (day 1). Control cows (n= 14) were synchronized but did not receive SP. Uterine biopsies were obtained from all cows on day 7 using the uterine horn ipsilateral to the ovulation site. The SP metabolome of HF and LF bulls could be discriminated based on the metabolites methionine sulfoxide, uracil, ornithine, L-cysteine, tetradecanoylcarnitine, decanoylcarnitine, adenosine monophosphate, cyclic AMP, lysoPC(18:1(9Z)), PC(16:1(9Z)/15:0), L-kynurenine, and cytosine. When compared with control cows, SP from HF bulls induced an upregulation of metabolites involved in energy metabolism and signaling including fumaric acid, isocitric acid, serotonin, uric acid, and PC (20:4/16:0). SP from LF bulls induced an upregulation of metabolites associated with stress and inflammation such as trimethylamine N-oxide (TMAO) and oxidized glutamate, and including serotonin, stearoylcarnitine, and fumaric acid. The findings were interpreted to indicate that SP from HF bulls induced an endometrial metabolome supportive of embryonic development, uterine receptivity and pregnancy, whilst SP from LF bulls induced a metabolome that was less supportive. This is the first study to report a relationship between the SP metabolome of high- and low-fertility males with the corresponding metabolome of uterine endometrium in vivo after intra-uterine deposition of seminal plasma • Seminal plasma (SP) metabolome differs in high (HF) and low (LF) fertility bulls. • HF SP is rich in antioxidants and arginine biosynthesis pathway metabolites. • Intrauterine HF SP upregulates endometrial energy metabolism and signaling. • LF SP induces endometrial markers of oxidative stress and inflammation. • Male fertility factors influence the uterine metabolome.