The Role Of HDAC3 In The Initiation Of Meiosis In Mouse Fetal Ovarian Germ Cells

During the reproduction,the bisexual gametes is the source of life.And the orderly process of gametogenesis is the vital cornerstone for reproduction.Meiosis determines the reproductive potential of the organism.The initiation of meiosis is strictly regulated by many genes.HDAC3 has the enzyme activity removed histone acetylation modification.It is believed that HDAC3,as pathogenic factor,is crucial epigenetic regulator.As we know,HDAC3 maintains the low acetylation state of Tubulin-K40 during metaphase meiosis of oocytes,which is a necessary condition for spindle assembly in metaphase meiosis of mouse oocytes.In addition,in the stage of oocyte maturation,only when the expression of HDAC3 is reduced,and then the inhibition of AREG is released,finally,the oocytes resume meiosis and continue to develop.However,in the initial stage of meiosis,the role and function of HDAC3 remains to be studied.To clarify the role of HDAC3 during the early period of meiosis of fetal oocytes.We inhibited HDAC3 activity in ovary during cultured in vitro.Subsequently,we detected and analyzed the biological process of germ cells and found that:(1)the number of oocyte entering meiosis was reduced after HDAC3 inhibition significantly in fetal ovary,and the germ cells did not enter meiosis gradually went to apoptosis;(2)after HDAC3 inhibition,results in the arrest of meiosis prophase I in the germ cells which have already initiated meiosis before HDAC3 inhibition;(3)HDAC3 inhibition affected the expression of some key genes at the initial stage of meiosis,among which the expressions of DAZL,SPO11,PRDM9 and ATM were significantly downregulated;(4)HDAC3 inhibition affected the localization of some key proteins at the initial stage of meiosis,among which yH2AX was abnormally located in the medial nuclear membrane,and SYCP3 was dispersed in the germ cells nucleus.Our results confirm the conclusion it is HDAC3 playing a momentous regulatory role in the initiation of meiosis of oocytes.Once HDAC3 is inhibited,the number of germ cells initiating meiosis was distinctly different from the usual.In addition,the expression of genes about meiosis is disordered,germ cells can not complete the transformation of cell division mode,and finally apoptosis is occurred.Hence,the mechanism of HDAC3 in the initial stage of meiosis is helpful to improve the molecular regulatory network of oocyte development.