Genetic merit for fertility alters the bovine uterine luminal fluid proteome†

Abstract

Over the last decades, fertility of dairy cows has declined due to selection strategies focusing on milk yield. To study the effect of genetic merit for fertility on the proteome of the bovine uterine luminal fluid, Holstein heifers with low- and two groups of heifers with high-fertility index (high-fertility Holstein and Montbéliarde) were investigated. To focus on the maternal effect, heifers from all groups were synchronized and received on Day 7 high-quality embryos. Uterine luminal fluid from Day 19 pregnant heifers was analyzed in a holistic proteomic approach using nano-LC-MS/MS analysis combined with a label-free quantification approach. In total, 1737 proteins were identified, of which 597 differed significantly in abundance between the three groups. The vast majority of proteome differences was found comparing both high-fertility groups to the low-fertility Holstein group, showing that the genetic predisposition for fertility is prevalent regarding the uterine luminal fluid proteome. Evaluation of this dataset using bioinformatic tools revealed an assignment of higher abundant proteins in low-fertility Holstein to several metabolic processes, such as vitamin metabolic process, which comprises folate receptor alpha (FOLR1) and retinol-binding protein, indicating an involvement of disturbed metabolic processes in decreased fertility. Moreover, immune system-related proteins — lactotransferrin and chromogranin A — were enriched in low-fertility cows together with interferon tau 3 h and interferon tau-2. Our results indicate that the genetic merit for fertility leads to substantial quantitative differences at the level of proteins in uterine fluid of pregnant animals, thus altering the microenvironment for the early conceptus.

Symposium review: Progesterone effects on early embryo development in cattle

“…Fructose and mannitol/sorbitol were elevated by 18.4 and 28.4-fold, respectively, in the ULF of high versus normal P4 heifers on d 12 (Simintiras et al, 2019c), suggestive of a key role for these metabolites in sustaining, in addition to initiating, conceptus elongation. Consistent with these observations, one of the proteins with very high abundance alteration between high-fertility and low-fertility heifers was sorbitol dehydrogenase, with14.3-and 11.1-fold increases in highfertility Holstein and Montbéliarde heifers compared with low-fertility Holsteins, respectively (Gegenfurtner et al, 2020). Sorbitol dehydrogenase, which is known to be located in the extracellular space, is required for the conversion of glucose to fructose by oxidation of sorbitol and has been shown to be expressed in porcine GE and LE during the peri-implantation period (Steinhauser et al, 2016).…”

Proteomic profiles of uterine fluids from health and repeat breeder Holstein cows

“…And some of these proteins can be used as biomarker proteins to predict diseases. All these ndings may provide new ideas and directions for us to better understand the biological mechanism of repeat breeder 3,4 .…”

Proteomic Approaches to Unravel the Molecular Dynamics of Early Pregnancy in Farm Animals: An In-Depth Review

“…To enhance the milk yield in dairy cows, single trait selection has been extensively used; however, it has led to a decline in fertility in high-yielding dairy cows [ 76 , 77 ]. In a recent study, Gegenfurtner et al investigated the effect of genetic merit for fertility on the proteome of the bovine uterine luminal fluid from Day 19 of pregnancy [ 77 ].…”

“…To enhance the milk yield in dairy cows, single trait selection has been extensively used; however, it has led to a decline in fertility in high-yielding dairy cows [ 76 , 77 ]. In a recent study, Gegenfurtner et al investigated the effect of genetic merit for fertility on the proteome of the bovine uterine luminal fluid from Day 19 of pregnancy [ 77 ]. Using nanoLC-MS/MS coupled with a label-free quantification approach, they identified 597 DEPs between the three groups: heifers with a low fertility index (Holstein) and two groups of heifers with a high fertility index (Holstein and Montbéliarde) [ 77 ].…”