DHEA protects mitochondria against dual modes of apoptosis and necroptosis in human granulosa HO23 cells

Abstract

Because ovarian granulosa cells are essential for oocyte maturation and development, we validated human granulosa HO23 cells to evaluate the ability of the DHEA to prevent cell death after starvation. The present study was aimed to investigate whether DHEA could protect against starvation-induced apoptosis and necroptosis in human oocyte granulosa HO23 cells. The starvation was induced by treatment of serum-free (SF) medium for 4 h Starvation-induced mitochondrial depolarization, cytochrome release and caspase-3 activation were largely prevented by DHEA in HO23 cells. We found that treatment with DHEA can restore starvation-induced reactive oxygen species (ROS) generation and mitochondrial membrane potential imbalance. In addition, treatment of DHEA prevents cell death via upregulation of cytochrome and downregulation of BAX in mitochondria. Most importantly, DHEA is ameliorated to mitochondrial function mediated through the decrease in mitochondrial ROS, maintained mitochondrial morphology, and enhancing the ability of cell proliferation and ROS scavenging. Our present data strongly indicate that DHEA reduces programmed cell death (apoptosis and necroptosis) in granulosa HO23 cells through multiple interactions with the mitochondrion-dependent programmed cell death pathway. Taken together, our data suggest that the presence of DHEA could be beneficial to protect human oocyte granulosa HO23 cells under culture conditions during various assisted reproductive technology (ART) programs.Free Chinese abstract: A Chinese translation of this abstract is freely available at http://www.reproduction-online.org/content/154/2/101/suppl/DC1.

Estrogen Effects on Wound Healing

“…The three major forms of estrogens in humans are estradiol, estrone, and estriol, with estradiol being the predominant form [ 31 , 32 , 33 , 34 , 35 ]. The ovary is the main source of estrogen in the premenopausal period, and granulosa cells are the key cells to produce estrogen [ 36 , 37 , 38 , 39 , 40 ]. Estrogen is also synthesized in skin tissue [ 41 ], presenting a concept termed “intracrinology” [ 42 ].…”

Dehydroepiandrosterone (DHEA) supplementation improves in vitro fertilization outcomes of poor ovarian responders, especially in women with low serum concentration of DHEA-S: a retrospective cohort study

“…However, direct action of DHEA on the target organs has been proposed [ 42 , 43 ] but is still inconclusive. Regarding the molecular mechanism, our previous studies revealed that DHEA supplementation could improve mitochondrial function and reduce apoptosis in the cumulus cells [ 44 ] and human granulosa cell line [ 45 ].…”

Dehydroepiandrosterone Ameliorates Abnormal Mitochondrial Dynamics and Mitophagy of Cumulus Cells in Poor Ovarian Responders

“…Therefore, enhancing mitochondrial biogenesis may result in an improvement of oocyte and embryo quality and, subsequently, better pregnancy outcomes because increased mitochondrial energy production may decrease chromosomal aneuploidies, improve embryo cleavage, and reduce cytoplasmic fragmentation [ 52 ]. Our previous studies showed that DHEA could increase mitochondrial function and activity, and reduce apoptosis and cell necroptosis in CCs and human granulosa cell line [ 3 , 4 , 53 ]. In addition, we found that DHEA might slow the aging of CCs [ 17 ].…”

“…Our previous studies demonstrated that mitochondrial function was significantly impaired in cumulus cells (CCs) from the POR group, and in human granulosa cells in vitro from the serum free group compared with the control group [ 3 , 4 ]. Hence, considering the importance of mitochondrial function in the oocyte, it is not surprising that oocyte quality decreases with increasing mitochondrial dysfunction [ 5 ].…”