Abstract
Heat stress induces apoptosis in various cells. Selenium, an essential micronutrient, has beneficial effects in maintaining the cellular physiological functions. However, its potential protective action against chronic heat stress (CHS)-induced apoptosis in granulosa cells and the related molecular mechanisms are not fully elucidated. In this study, we investigated the roles of selenium in CHS-induced apoptosis in mouse granulosa cells and explored its underlying mechanism. The heat treatment for 6–48 h induced apoptosis, potentiated caspase 3 activity, increased the expression levels of apoptosis-related gene BAX and ER stress markers, glucose-regulated protein 78 (GRP78), and CCAAT/enhancer binding protein homologous protein (CHOP) in mouse granulosa cells. The treatment with ER stress inhibitor 4-PBA significantly attenuated the adverse effects caused by CHS. Selenium treatment significantly attenuated the CHS- or thapsigargin (Tg, an ER stress activator)-induced apoptosis, potentiation of caspase 3 activity, and the increased protein expression levels of BAX, GRP78, and CHOP. Additionally, treatment of the cells with 5 ng/mL selenium significantly ameliorated the levels of estradiol, which were decreased in response to heat exposure. Consistently, administering selenium supplement alleviated the hyperthermia-caused reduction in the serum estradiol levels in vivo. Together, our findings indicate that selenium has protective effects on CHS-induced apoptosis via inhibition of the ER stress pathway. The current study provides new insights in understanding the role of selenium during the process of heat-induced cell apoptosis.
Highlights
Heat stress is a non-specific response to the thermal environment, which is known to be a major risk factor for diminishing reproductive efficiency and performance usually in female mammals during summer [1,2]
We have shown that chronic heat stress had adverse effects on the mouse granulosa cells including the reduction in cell viability, induction of apoptosis, potentiation of caspase 3 activity, and upregulation of the expression of apoptosis-related crucial protein BAX
A prior study has reported that the expression levels of caspase-3 are upregulated, and that the mitochondrial apoptotic pathway is involved in the acute heat stress-induced apoptosis in the mouse granulosa cells that suffer the high temperature treatment [24]
Summary
Heat stress is a non-specific response to the thermal environment, which is known to be a major risk factor for diminishing reproductive efficiency and performance usually in female mammals during summer [1,2]. The existing evidence shows that heat stress causes abnormal follicular atresia, steroid hormone secretion disorder in the ovary, and even female infertility [3]. As compared to acute heat stress, the intensity of these effects is relatively weak in chronic heat stress. It is well known that granulosa cell apoptosis is an important marker and inducer of follicular atresia, and it plays critical roles in sustaining the normal physiological functions of the ovary, such as follicular growth and hormone synthesis [5]. Previous studies have shown that heat stress inhibits proliferation and induces apoptosis of ovarian granulosa cells, which were closely related to ovarian dysfunction induced by heat stress in various species [6,7,8]
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