Exosomal Cargo May Hold the Key to Improving Reproductive Outcomes in Dairy Cows

Abstract

The reproductive status of dairy cows remains a challenge for dairy farmers worldwide, with impaired fertility linked to a significant reduction in herd profitability, due in part to impaired immunity, increased metabolic pressure, and longer postpartum anestrous interval (PPAI). Exosomes are nanovesicles released from a variety of cell types and end up in circulation, and carry proteins, bioactive peptides, lipids, and nucleic acids specific to the place of origin. As such, their role in health and disease has been investigated in humans and animals. This review discusses research into exosomes in the context of reproduction in dairy herds and introduces recent advances in mass-spectrometry (MS) based proteomics that have a potential to advance quantitative profiling of exosomal protein cargo in a search for early biomarkers of cattle fertility.

Keywords: SWATH; dairy cow; exosome; fertility; mass-spectrometry; proteomics; reproduction.

Figure 1

Routes of exosomal formation and release from the cell. The Golgi apparatus (1) transports and modifies proteins received from the endoplasmic reticulum (ER). Mature proteins and proproteins are transferred from the Golgi to endosomes via transport vesicles (2a and 3). Early endosomes go on to form late endosomes/multivesicular bodies (MVBs) (4 and 5), which are composed of intraluminal vesicles (ILVs) formed from the inward budding of the endosomal membrane during the maturation process. Endosomal sorting complex required for transport (ESCRT) proteins are involved in this process and are found in ILV cargo. MVBs fuse with the plasma membrane of the cell to release their contents into the extracellular milieu; extracellular vesicles (EVs) (6). EVs are taken up by the cell via endocytosis or phagocytosis (2b) and transported to endosomal compartments and lysosomes for processing [37].

Figure 2

Blended model of reproduction and inflammation: Arachidonic Acid (AA)/Eicosanoid Pathway. Fatty acid cyclooxygenase 1/2 (Cox 1/2) converts AA to downstream effector molecules (Prostanoids and Prostaglandins (PGs)) following inflammatory stimuli. Interferon-tau (IFN-τ) produced by the conceptus inhibits Oxytocin receptor (Oxtr) expression and prevents luteolysis of luteinized granulosa cells to maintain progesterone secretion. IFN-τ stimulates PGE₂ production in the endometrium, resulting in structural and functional changes required for pregnancy recognition. In vitro studies show altered expression of PGF_2α and PGE₂ when exposed to inflammatory stimuli, which in turn may compromise events leading to successful establishment of pregnancy. Nonsteroidal anti-inflammatory drugs (NSAIDs) target the PG inflammatory cascade by inhibiting Cox2 expression and reducing production of PGH₂ and associated inflammatory mediators.