Hazardous Effects of Curcumin on Mouse Embryonic Development through a Mitochondria-Dependent Apoptotic Signaling Pathway

Abstract

In this study, we examined the cytotoxic effects of curcumin, the yellow pigment of Curcuma longa, on the blastocyst stage of mouse embryos, subsequent embryonic attachment, and outgrowth in vitro and in vivo implantation by embryo transfer. Mouse blastocysts were incubated in medium with or without curcumin (6, 12 or 24 μM) for 24 h. Cell proliferation and growth were investigated using dual differential staining, apoptosis was analyzed with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), and implantation and post-implantation development of embryos were measured by in vitro development analysis and in vivo embryo transfer, respectively. Blastocysts treated with 24 μM curcumin displayed significantly increased apoptosis and decreased total cell number. Interestingly, we observed no marked differences in the implantation success rates between curcumin-pretreated and control blastocysts during in vitro embryonic development through implantation with a fibronectin-coated culture dish. However, in vitro treatment with 24 μM curcumin was associated with decreased implantation rate and increased resorption of postimplantation embryos in mouse uterus, as well as decreased fetal weight in the embryo transfer assay. Our results collectively indicate that in vitro exposure to curcumin triggers apoptosis and retards early postimplantation development after transfer to host mice. In addition, curcumin induces apoptotic injury effects on mouse blastocysts through ROS generation, and further promotes mitochondria-dependent apoptotic signaling processes to impair sequent embryonic development.

Caspase-9 inhibitor Z-LEHD-FMK enhances the yield of in vitro produced buffalo (Bubalus bubalis) pre-implantation embryos and alters cellular stress response

“…These results are in agreement with the results of Loureiro et al (2007) and Chen et al (2010) which showed that the use of Z-LEHD-FMK in bovine pre implantation embryos decreased the number of apoptotic cells. In human Z-LEHD-FMK decreased the TRAIL induced apoptosis in the non-cancerous cells (Ozoren et al, 2000).…”

“…Reduced apoptosis leads to the increase in rate of early development and better survival of embryonic cells (Loureiro et al, 2007). Chen et al (2010) used caspase-9 (Z-LEHD-FMK) and caspase-3 (Z-DEVD-FMK) in curcumin treated mouse blastocysts and found more survival of blastomere cells.…”

Steroidogenic acute regulatory protein (StAR) and peripheral-type benzodiazepine receptor (PBR) are decreased in human apoptotic embryos

“…It was reported that the level of ROS increases drastically while the active mitochondrial membrane potential decreases within embryos that are in vitro cultured and abnormality is induced in the mitochondria (Chen et al 2003). These changes would stop the embryonic development and induce apoptosis (Sohn et al 2002;Chen et al 2010). In this study we confirmed that mitochondrial membrane potential was reduced in the human preimplantation embryos showing fragmentation.…”

Injurious Effects of Curcumin on Maturation of Mouse Oocytes, Fertilization and Fetal Development via Apoptosis

“…Previously, we showed that curcumin induces apoptosis, impairment of blastocyst development from the morula, and promotion of early-stage death of mouse blastocysts [22]. Thus, it is important to establish the possible teratogenic effects of curcumin.…”