Protective effects of β-carotene on lipopolysaccharide-induced endoplasmic reticulum stress in porcine cumulus cells

Abstract

Abstract Gram-negative bacterial infection is one of the leading causes of impaired ovarian function and fertility, which is closely related to the adverse effects of the endotoxin lipopolysaccharide (LPS). β-Carotene is a natural antioxidant with powerful anti-inflammatory and anti-apoptotic effects. To explore whether LPS exposure could exert adverse effects on porcine cumulus cells and whether β-carotene could relieve the stress caused by LPS exposure, the porcine cumulus oocyte complexes (COCs) were treated with 2.5, 5, 10 and 20 µg/mL LPS alone or cotreated with 2.5, 5 and 10 µM β-carotene during in vitro maturation for 44 h. The results show that cumulus expansion was observably inhibited and that the first polar body (PB1) extrusion rate was also significantly decreased when the concentration of LPS reached 10 µg/mL. In addition, higher expression levels of GRP78 and upregulated unfolded protein response (UPR)-related genes (PERK, IRE1, and ATF4) were detected in LPS-treated cumulus cells. Moreover, the proportion of apoptotic cells significantly increased, the expression of the endoplasmic reticulum stress (ERS)-related apoptotic gene (CHOP) was upregulated, and the downstream apoptotic program was subsequently activated. Conversely, the 5 µM β-carotene cotreatment could effectively alleviate the adverse effects of LPS exposure, showing the improvement of cumulus expansion and PB1 extrusion. Moreover, β-carotene supplementation significantly alleviated LPS-triggered ERS and thus inhibited the subsequent ERS-induced apoptotic program in cumulus cells. Collectively, these results indicated that LPS exposure exerted adverse effects on porcine cumulus cells and that β-carotene could exhibit protective effects on LPS-induced cumulus cell dysfunction by allaying apoptosis via restriction of ERS.