|
Comment |
HDAC6 regulates primordial follicle activation through mTOR signaling pathway. Zhang T et al. (2021) Primordial follicle pool established perinatally is a non-renewable resource which determines the female fecundity in mammals. While the majority of primordial follicles in the primordial follicle pool maintain dormant state, only a few of them are activated into growing follicles in adults in each cycle. Excessive activation of the primordial follicles accelerates follicle pool consumption and leads to premature ovarian failure. Although previous studies including ours have emphasized the importance of keeping the balance between primordial follicle activation and dormancy via molecules within the primordial follicles, such as TGF-β, E-Cadherin, mTOR, and AKT through different mechanisms, the homeostasis regulatory mechanisms of primordial follicle activation remain unclear. Here, we reported that HDAC6 acts as a key negative regulator of mTOR in dormant primordial follicles. In the cytoplasm of both oocytes and granulosa cells of primordial follicles, HDAC6 expressed strong, however in those activated primordial follicles, its expression level is relatively weaker. Inhibition or knockdown of HDAC6 significantly promoted the activation of limited primordial follicles while the size of follicle pool was not affected profoundly in vitro. Importantly, the expression level of mTOR in the follicle and the activity of PI3K in the oocyte of the follicle were simultaneously up-regulated after inhibiting of HDAC6. The up-regulated mTOR leads to not only the growth and differentiation of primordial follicles granulosa cells (pfGCs) into granulosa cells (GCs), but the increased secretion of KITL in these somatic cells. As a result, inhibition of HDAC6 awaked the dormant primordial follicles of mice in vitro. In conclusion, HDAC6 may play an indispensable role in balancing the maintenance and activation of primordial follicles through mTOR signaling in mice. These findings shed new lights on uncovering the epigenetic factors involved physiology of sustaining female reproduction.//////////////////
Histone deacetylase 6 (HDAC6) is an essential factor for oocyte maturation and asymmetric division in mice. Zhou D et al. (2017) Tubastatin A (Tub-A), a highly selective histone deacetylase 6 (HDAC6) inhibitor, has been widely used as a cytotoxic anticancer agent, or for the treatment of patients with asthma. However, the potential toxicity of Tub-A on oocyte maturation and asymmetric division is still unclear. Therefore, the present study was designed to examine the effect and potential regulatory role of Tub-A on the meiotic maturation of oocytes. We observed that Tub-A treatment induced an increased level of the acetylation of α-tubulin, and a failure of spindle migration and actin cap formation. Based on the spindle structure, most Tub-A treated oocytes were arrested in an MI-like or a GVBD-like stage and exhibited decondensed chromosomes in a dose dependent manner. Moreover, Tub-A treatment decreased the protein expression of mTOR, a factor responsible for spindle formation, and the expression of mDia1, an inhibitor of actin assembly, in an HDAC6 expression-dependent manner. Importantly, following Tub-A supplementation, most oocytes failed to extrude the first polar body, which indicates that these defects are closely linked to abnormal oocyte maturation. Taken together, our data demonstrates that HDAC6 is one of the essential factors for oocyte maturation and asymmetric division via the HDAC6/mTOR or mDia1 pathway in mice.////////////////// . HDAC6 inhibition disrupts maturational progression and meiotic apparatus assembly in mouse oocytes. Ling L et al. (2017) Histone deacetylases (HDACs) have been implicated in diverse biological processes including transcriptional regulation, signal transduction, and developmental control. However, the role of HDAC6 in mammalian oocytes remains unknown. In the present study, by employing Tubastatin A (TubA), a selective HDAC6 inhibitor, we examined the effects of HDAC6 on maturational progression and meiotic apparatus in mouse oocytes. We found that HDAC6 inhibition results in maturation arrest and disruption of spindle morphology and chromosome alignment. In line with this observation, confocal microscopy revealed that kinetochore-microtubule attachment, a critical mechanism controlling chromosome movement, is compromised in TubA-treated oocytes markedly. Moreover, we noted that HDAC6 inhibition significantly increases the acetylation levels of α-tubulin in mouse oocytes, which may be associated with the defective phenotypes of TubA-treated oocytes by altering microtubule stability and dynamics. In sum, we discover a novel function of HDAC6 during oocyte maturation and suggest a potential pathway modulating meiotic apparatus assembly.////////////////// analysis of mouse oocytes reveals 28 candidate factors of the 'reprogrammome' Boiani M et al. The oocyte is the only cell of the body that can reprogram transplanted somatic nuclei, and sets the gold standard for all reprogramming methods. Therefore, an in-depth characterization of its proteome holds promise to advance our understanding of reprogramming and germ cell biology. To date, limitations on oocyte numbers and proteomic technology have impeded this task, and the search for reprogramming factors has been conducted in embryonic stem (ES) cells instead. Here, we present the proteome of metaphase II mouse oocytes to a depth of 3699 proteins, which substantially extends the number of proteins identified until now in mouse oocytes and is comparable by size to the proteome of undifferentiated mouse ES cells. Twenty-eight oocyte proteins, also detected in ES cells, match the criteria of our multi-level approach to screen for reprogramming factors, namely: nuclear localization, chromatin modification and catalytic activity. Our oocyte proteome catalog thus advances the definition of the 'reprogrammome', the set of molecules - proteins, RNAs, lipids and small molecules - that enable reprogramming.
|