Distribution pattern of cytoplasmic organelles, spindle integrity, oxidative stress, octamer-binding transcription factor 4 (Oct4) expression and developmental potential of oocytes following multiple superovulation

Abstract

The aim of the present study was to determine the effects of repeated superovulation on oocyte quality and embryo developmental potential. Female Swiss albino mice were injected with 5IU pregnant mare's serum gonadotropin followed 48h by 10IU human chorionic gonadotropin. Mice were superovulated up to four times with a gap of 7 days between each superovulation cycle. Ovarian weight increased significantly with an increasing number of superovulation cycles. Although the first stimulation cycle resulted in a threefold increase in the number of oocytes, the number of oocytes decreased gradually after subsequent stimulations. Increased cytoplasmic fragmentation, abnormal mitochondrial distribution, aggregation of Golgi apparatus, spindle damage, increased intracellular oxidative stress and a decrease in expression of octamer-binding transcription factor 4 (Oct4) expression were observed in these oocytes. Further, embryos derived from mice subjected to multiple stimulation cycles exhibited a low blastocyst rate, decreased hatching rate and increased apoptosis in blastocysts. In conclusion, the present study demonstrates that repeated superovulation adversely affects mouse oocyte quality by altering the distribution of cytoplasmic organelles, increasing oxidative stress and decreasing Oct4 expression, resulting in poor developmental potential of the embryos.

Adverse Effect of Superovulation Treatment on Maturation, Function and Ultrastructural Integrity of Murine Oocytes

“…While superovulation treatment has become the basic methodology of human and animal ART programs, it has been reported that decreased quality of superovulated oocytes before and after IVF resulted the reduced fecundity. Increased preimplantation mortality after superovulation has been reported in mice ( Beaumont and Smith, 1975 ; Ertzeid and Storeng, 1992 ; Kalthur et al, 2015 ) and rats ( Miller and Armstrong, 1981 ). Ovarian hyperstimulation can increase chromosomal abnormalities in murine embryos ( Elbling and Colot, 1985 ; Huffman et al, 2015 ; Luckett and Mukherjee, 1986 ; Ozturk et al, 2016 ), and mitochondrial deformity further induced oocyte aneuploidy ( Plachot, 2003 ; Takeuchi et al, 2005 ).…”

Repeated superovulation may affect mitochondrial functions of cumulus cells in mice

“…Additionally, repeated superovulation affects ovarian structure and function in rhesus monkeys 13 . Multiple superovulation phases changed the organelle distribution in mouse oocytes 14 . These data indicate that repeated superovulation reduces oocyte quality, but the mechanism remains unclear.…”

Melatonin alleviates the deterioration of oocytes from mice subjected to repeated superovulation

“…**p < 0.01, ***p < 0.001. 5mc: 5-methylcytosine [Color figure can be viewed at wileyonlinelibrary.com] Albertini, 2003; Kalthur et al, 2016;Xie et al, 2016). By using a murine model, we found that repeated superovulation reduces oocyte quality by disrupting meiotic cytoskeletal assemblies, mitochondrial function, and genomic DNA methylation; elevating oocyte apoptosis; and inducing oxidative stress.…”