Research Article: Sirtuin Inhibition Adversely Affects Porcine Oocyte Meiosis

Date Published: July 15, 2015

Publisher: Public Library of Science

Author(s): Liang Zhang, Rujun Ma, Jin Hu, Xiaolin Ding, Yinxue Xu, Meijia Zhang.


Sirtuins have been implicated in diverse biological processes, including oxidative stress, energy metabolism, cell migration, and aging. Here, we employed Sirtuin inhibitors, nicotinamide (NAM) and Sirtinol, to investigate their effects on porcine oocyte maturation respectively. The rate of polar body extrusion in porcine oocytes decreased after treatment with NAM and Sirtinol, accompanied with the failure of cumulus cell expansion. We further found that NAM and Sirtinol significantly disrupted oocyte polarity, and inhibited the formation of actin cap and cortical granule-free domain (CGFD). Moreover, the abnormal spindles and misaligned chromosomes were readily detected during porcine oocyte maturation after treatment with NAM and Sirtinol. Together, these results suggest that Sirtuins are involved in cortical polarity and spindle organization in porcine oocytes.

Partial Text

Maturation of mammalian oocytes is characterized by breakdown of the germinal vesicle (GV), followed by chromatin condensation and reorganization of microtubules during first meiosis (MI). Subsequently, the spindle migrates along its long axis toward the oocyte cortex, and emission of the first polar body occurs in the metaphase of second meiosis (MII). The fully matured oocytes are arrested at metaphase II until fertilization [1]. Oocyte maturation involves two aspects, cytoplasmic and nuclear maturation. Both steps are essential for the formation of a fertilizable egg that can subsequently develop into a live offspring. Nuclear maturation primarily includes chromosomal condensation and segregation. Cytoplasmic maturation refers to the processes that prepare the egg for activation and preimplantation development [2]. Actin is important for mammalian oocyte maturation. Actin cytoskeleton is involved in asymmetric spindle positioning and cortical polarization during meiotic division in all organisms from mice to humans [3–8]. Lenart et al. have demonstrated that chromosome congression is driven by the actin network [9], and the actin-enriched cortical domain promotes the extrusion of the first polar body during myosin assembly [10–12]. Moreover, the distribution of cortical granules (CGs) during oocyte maturation has been used as a critical criterion to assess cytoplasmic maturation. CGs of mature oocytes migrate to the cortex to form a continuous layer overlying the oolemma [13–16]. In summary, oocyte maturation is a complex biological process, and development of oocyte polarity involves the assembly of actin and CGs.

The studies presented here were designed to investigate the roles of Sirtuins on porcine oocyte meiotic maturation by using inhibitors NAM and Sirtinol, which block Sirtuin activity. The results indicated that NAM and Sirtinol treatment reduced the rate of polar body extrusionand disrupted actin assembly in porcine oocytes. Moreover, inhibition of Sirtuin activity led to spindle defects and absence of CGFD. The study provides the evidence that Sirtuins are involved in meiotic maturation in porcine oocytes.