Mitigation of ER stress improves bovine in vitro embryo development and pregnancy rates.

Abstract

Endoplasmic reticulum (ER) stress compromises cellular homeostasis in multiple cell types, gametes and early embryos are particularly susceptible, with negative consequences for developmental competence. This study investigated the effects of ER stress and its attenuation by TUDCA at specific developmental stages of bovine embryos and evaluated ER stress-modulating compounds in a commercially in vitro embryo production (IVEP) system. To induce ER stress, embryos were exposed to tunicamycin (TN; 0.1, 1, and 10 ng/mL) during in vitro culture (IVC). Stage-specific sensitivity to ER stress was assessed by treating embryos 1 ng/mL TN during periods associated with embryonic genome activation (EGA): pre-EGA (days 1-3), EGA (days 3-5), and post-EGA (days 5-7). The ability of the bile acid tauroursodeoxycholic acid (TUDCA) to alleviate ER stress was then examined. Embryos received combined TN and TUDCA treatments either throughout culture or specifically during EGA, and outcomes were compared with TN alone. Finally, TUDCA supplementation was tested under commercial IVEP conditions. TN at 1 and 10 ng/ml dose-dependently reduced embryo development during in vitro culture (Days 1-7). Embryo development and total cell number were also decreased by 1 ng/ml TN during EGA (Days 3-5). TUDCA supplementation (100 μM) increased total cell number and the proportion of expanded blastocysts compared to controls and effectively mitigated TN-induced damage. In commercial IVEP, TUDCA supplementation increased blastocyst yield by ∼11% in beef cattle and improved pregnancy rates by 24.1% in dairy cattle. These results highlight the importance of ER stress during key embryo developmental stages and support the use of TUDCA as a beneficial supplement to enhance outcomes in commercial bovine IVEP systems.