RNA binding protein IGF2BP1 meditates oxidative stress-induced granulosa cell dysfunction by regulating MDM2 mRNA stability in an m6A-dependent manner.

Both genetic and microenvironmental detrimental factors are involved in ovarian dysfunction, leading to the increasing rate of involuntary childlessness in recent years. Oxidative stress (OS), which is characterized by the imbalance of redox system with redundant reactive oxygen species (ROS) overwhelming the antioxidant defense, is regarded as one of the culprits of ovarian dysfunction. OS causes damage to various types of ovarian cells including granulosa cells (GCs), jeopardizing the ovarian microenvironment, disturbing follicular development and participating in various female reproductive disorders. However, the specific molecular pathological mechanisms underlying this process have not been fully elucidated. In this study, we found that 3-nitropropionic acid (3-NP) treatment led to significant IGF2BP1 downregulation via, at least partially, inducing ROS overproduction. IGF2BP1 regulates GCs viability, proliferation, cell cycle and cellular senescence by enhancing MDM2 mRNA stability in an m6A-dependant manner. IGF2BP1 overexpression partially rescued 3-NP induced GCs damages, while ectopically expressed MDM2 alleviated both 3-NP or IGF2BP1-knockdown induced GCs dysfunction. These results reveal an epigenetic molecular mechanism underlying OS-related GCs disorders, which may help to establish a novel potential clinical marker for predicting the GCs status as well as the follicular developmental potential.

The potential of Zishen Yutai pills to facilitate endometrial recovery and restore fertility after induced abortion in rats.

CONTEXT: Abortions damage the endometrium in women. Currently, therapeutic options for endometrial recovery are limited. Zishen Yutai Pill (ZYP) was found to promote endometrial blood supply as a traditional Chinese medicine. However, whether ZYP promotes endometrial recovery post-abortion has not yet been explored. OBJECTIVE: This study evaluated the role of ZYP in rat endometrial recovery after induced abortion and explored its mechanism of action. MATERIALS AND METHODS: Sprague-Dawley rats were divided into three groups: no-operation group, control group, and ZYP group. The rats in the control and ZYP group were induced abortion, and then treated with normal saline or ZYPs, respectively, for 1-3 oestrous cycles. Morphological changes in the endometrium were examined. Expression levels of the factors related to endometrial recovery were analyzed. The duration of this study was almost seven months. RESULTS: The endometrial thickness (7.3 ± 0.17 mm) and number of glands (5.5 ± 0.20) increased significantly in the ZYP group compared with those in the control group (5.5 ± 0.15 mm and 3.5 ± 0.18; p < 0.05). Fibrosis of the endometrium was ameliorated by ZYP administration (45 ± 6% vs. 58 ± 7%; p < 0.05). ZYPs treatment increased the expression of VEGF, ER, MMP-9, LIF, and HB-EGF, but decreased TGF-ß expression. Moreover, the average number of pups in the ZYP group (9.0 ± 1.5) was greater than that in the control (4 ± 1.3). DISCUSSION AND CONCLUSION: ZYPs accelerate endometrial recovery and restored fertility in rats, suggesting its potential to promote human endometrial repair.

Mitochondrial dysfunction during in vitro hepatocyte steatosis is reversed by omega-3 fatty acid-induced up-regulation of mitofusin 2.

We examined the effects and mechanisms of omega-3 polyunsaturated fatty acid (PUFA) administration on mitochondrial morphology and function in an in vitro steatotic hepatocyte model created using HepG2 cells. Reverse transcriptase polymerase chain reaction and Western blot analyses were performed to determine the expression levels of mitofusin 2 (Mfn2), and immunofluorescent MitoTracker Mitochondrion-Selective Probes were used to detect changes in mitochondrial morphology. Adenosine triphosphate (ATP) synthesis and reactive oxygen species (ROS) production were measured to assess mitochondrial function. Mitofusin 2 expression was significantly suppressed (P < .05), ATP levels were decreased (P < .05), ROS production was increased (P < .05), and the normal tubular network of mitochondria was fragmented into short rods or spheres. Model cells were incubated with eicosapentaenoic acid or docosahexaenoic acid at a final concentration of 50 µmol/L for 1 hour. Both eicosapentaenoic acid and docosahexaenoic acid increased the expression of Mfn2 (P < .01) and caused an increase in the length of mitochondrial tubules. The omega-3 PUFAs also increased the levels of ATP (P < .05) and decreased the ROS production (P < .05). However, these changes were not seen in Mfn2-depleted steatotic HepG2 cells, created by RNA interference before incubation with the omega-3 PUFAs. This study demonstrated that, in steatotic hepatocytes, omega-3 PUFAs may change mitochondrial morphology and have beneficial effects on recovery of mitochondrial function by increasing the expression of Mfn2.