Influence of metabolic status and genetic merit for fertility on proteomic composition of bovine oviduct fluid†

Abstract

The oviduct plays a crucial role in fertilization and early embryo development providing the microenvironment for oocyte, spermatozoa, and early embryo. Since dairy cow fertility declined steadily over the last decades, reasons for early embryonic loss have gained increasing interest. Analyzing two animal models, this study aimed to investigate the impact of genetic predisposition for fertility and of metabolic stress on the protein composition of oviduct fluid. A metabolic model comprised maiden Holstein heifers and postpartum lactating (Lact) and non-lactating (Dry) cows, while a genetic model consisted of heifers from the Montbéliarde breed and Holstein heifers with low- and high-fertility index. In a holistic proteomic analysis of oviduct fluid from all groups using nano-liquid chromatography tandem-mass spectrometry analysis and label-free quantification, we were able to identify 1976 proteins, among which 143 showed abundance alterations in the pairwise comparisons within both models. Most differentially abundant proteins were revealed between low fertility Holstein and Montbéliarde (52) in the genetic model and between lactating and maiden Holstein (19) in the metabolic model, demonstrating a substantial effect of genetic predisposition for fertility and metabolic stress on the oviduct fluid proteome. Functional classification of affected proteins revealed actin binding, translation, and immune system processes as prominent gene ontology (GO) clusters. Notably, Actin-related protein 2/3 complex subunit 1B and the three immune system-related proteins SERPIND1 protein, immunoglobulin kappa locus protein, and Alpha-1-acid glycoprotein were affected in both models, suggesting that abundance changes of immune-related proteins in oviduct fluid play an important role for early embryonic loss.

Composing the Early Embryonic Microenvironment: Physiology and Regulation of Oviductal Secretions

“…Accordingly, two weeks postpartum in lactating cows, when the energy balance is already negative, specific changes in insulin growth factor-binding protein (IGF-BP) expression were reported in the oviduct [101]. Recent data indicate that, at the expected time of conception (60 days postpartum), the transcriptome of isthmus epithelial cells and proteomic composition of oviductal fluid differed between age-paired Holstein lactating and non-lactating cows [66,102]. The changes in gene and protein expression were moderate; only 15 DEGs and 12 differentially abundant proteins were identified between age-paired lactating and non-lactating cows [66,102].…”

“…Recent data indicate that, at the expected time of conception (60 days postpartum), the transcriptome of isthmus epithelial cells and proteomic composition of oviductal fluid differed between age-paired Holstein lactating and non-lactating cows [66,102]. The changes in gene and protein expression were moderate; only 15 DEGs and 12 differentially abundant proteins were identified between age-paired lactating and non-lactating cows [66,102]. Nevertheless, lactation strongly altered the effect of proximity to corpus luteum on oviduct gene expression.…”

“…Comparison between OECs from postpartum lactating and non-lactating dairy cows evidenced 15 DEGs in the isthmus and none in the ampulla [66] Energy balance OF proteins Cattle Comparison between OF from postpartum lactating and non-lactating dairy cows evidenced 12 differentially abundant proteins [102]…”

Endometrium-on-a-chip reveals the endometrial transcriptome, and protein content of secretome are altered by changes in circulating concentrations of insulin and glucose in vitro

“…This occurs co-ordinately with establishing early pregnancy, and there is a growing body of evidence to suggest that this 4 metabolic stress in maternal circulation compromises the ability of the reproductive tract of the lactating dairy cow to support early development (11,12). Data indicates this metabolic stress alters global gene expression in the embryo/conceptus, the oviduct (9,13), and endometrium (13)(14)(15). Conceptuses derived from early in lactation are less developmentally competent (metabolic stress) compared to late stages of lactation (16).…”

“…nutritional insults, at specific developmental time points can alter an individual’s susceptibility to disease in later life (7). Despite advances in our understanding of the ULF composition (8, 9), efforts to supplement culture media with these components have not substantially improved development indicating there are likely still unknown components of ULF yet to be discovered.…”