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.
Highlights
A common dietary pigment and spice, is a hydrophobic polyphenol derived from the rhizome of the herb Curcuma longa that is used as a traditional Indian medicine [1] for the treatment of wounds, liver ailments, hepatitis and urinary tract diseases, as well as a cosmetic compound [2]
Our results show that curcumin suppresses embryonic cell proliferation during the blastocyst stage predominantly by inducing apoptosis in the inner cell mass (ICM)
The results revealed significantly lower total and ICM cell numbers in curcumin-treated blastocysts (24 μM) versus controls (Figure 2A)
Summary
A common dietary pigment and spice, is a hydrophobic polyphenol derived from the rhizome of the herb Curcuma longa that is used as a traditional Indian medicine [1] for the treatment of wounds, liver ailments, hepatitis and urinary tract diseases, as well as a cosmetic compound [2]. Another study by our group focusing on the possible effects of curcumin on ROS generation, intracellular adenosine triphosphate (ATP) levels and cell death mode in osteoblast cells revealed that curcumin induces apoptosis or necrosis in a dose-dependent manner [15]. The curcumin dosage was show to determine its possible effects on ROS generation, intracellular ATP levels, and apoptosis or necrosis in osteoblast cells [15]. These findings collectively indicate that curcumin promotes apoptosis or necrosis in a dose-dependent manner in human osteoblast cells. The mechanisms underlying curcumin-induced apoptosis of mouse blastocysts remain to be determined
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