Exposure to phenanthrene affects oocyte meiosis by inducing mitochondrial dysfunction and endoplasmic reticulum stress.

OBJECTIVES: Phenanthrene (PHE) is one of the most abundant polycyclic aromatic hydrocarbons (PAHs), which is a widespread environmental contaminant. Various studies showed that PHE has adverse impacts on animals and human health. It has been shown that PHE exposure induced follicular atresia and endocrine dyscrasia in female mice. However, the potential mechanism regarding how PHE affects female reproductive system especially the oocyte quality has not been elucidated. METHODS AND RESULTS: In this study, we set up PHE exposure model and found that PHE exposure compromised oocytes maturation competence by inhibiting spindle assembly and chromosomes alignment. Moreover, PHE exposure induced mitochondrial dysfunction and endoplasmic reticulum (ER) stress, leading to increased reactive oxygen species (ROS) and aberrant calcium levels in cytoplasm, eventually induced oxidative stress and DNA damage in oocytes. Furthermore, we found that oral administration of PHE caused the occurrence of oxidative stress and apoptosis in female ovary. In addition, the oocyte exhibited aberrant spindle morphology and failure of actin cap formation in metaphase II oocytes. CONCLUSIONS: Taken together, our study demonstrated that mitochondrial dysfunction and ER stress-induced oxidative stress and DNA damage are the major cause of poor oocyte quality after PHE exposure.

Melatonin protects against maternal diabetes-associated meiotic defects by maintaining mitochondrial function.

Maternal diabetes has been widely reported to adversely affect oocyte quality. Although various molecules and pathways may be involved in this process, strategies to prevent maternal diabetes-induced deterioration of oocyte quality remain unexplored. Melatonin is synthesized by the pineal gland and has been shown to have beneficial effects on oocyte quality owing to its antioxidative function. In the present study, we found that the exposure of oocytes of diabetic mice to melatonin, in vitro, alleviated aberrant oocyte maturation competence. Notably, melatonin supplementation attenuated defects in spindle organization and chromosome alignment by mediating the expression of TPX2 and pericentrin localization. Importantly, melatonin eliminated the accumulation of reactive oxygen species and increased the cytosolic Ca2+ levels in diabetic oocytes by maintaining mitochondrial function. Moreover, the occurrence of autophagy and apoptosis was reversed in diabetic oocytes after melatonin exposure via decreased LC3ß expression. Collectively, our findings provide evidence that melatonin supplementation can protect oocytes from maternal diabetes-related meiotic defects and poor egg quality, providing a potential strategy for improving oocyte quality in assisted reproductive technologies.

Perfluorooctanoic acid (PFOA) exposure affects early embryonic development and offspring oocyte quality via inducing mitochondrial dysfunction.

Perfluorooctanoic acid (PFOA) is a synthetic perfluorinated compound that is extensively used as an integral surfactant in commercial production. Owing to its hydrophilicity and persistence, PFOA can accumulate in living organisms and induce severe disease in animals and humans. It has been reported that PFOA exposure can affect ovarian function and induce reproductive toxicity; however, the effects and potential mechanism of PFOA exposure during gestation on early embryonic development and offspring remain unclear. This study found that PFOA exposure in vitro disrupted spindle assembly and chromosome alignment during the first cleavage of early mouse embryos, which impacted early embryonic cleavage and blastocyst formation. Moreover, PFOA exposure caused mitochondrial dysfunction and oxidative stress by inducing aberrant Ca2+ levels, liquid drops(LDs), and mitochondrial membrane potential in the 2-cell stage. Furthermore, we found that PFOA exposure resulted in DNA damage, autophagy, and apoptosis in 2-cell stage by inhibiting SOD2 function. Gestational exposure to PFOA significantly increased ovarian apoptosis and disrupted follicle development in F1 offspring. In addition, oocyte maturation competence was decreased in F1 offspring. Finally, single-cell transcriptome analysis revealed that PFOA-induced oocyte deterioration was caused by mitochondrial dysfunction and apoptosis in the F1 offspring. In summary, our results indicated that gestational exposure to PFOA had potential toxic effects on ovarian function and led to a higher incidence of meiotic defects in F1 female offspring.

Clinical features and surgical treatment of double elevator palsy in young children.

AIM: To describe the clinical features of congenital double elevator palsy (CDEP) and to evaluate various surgical outcomes between the standard Knapp and augmented Knapp procedures, based on improvements in primary eye position and ocular motility. METHODS: Twenty-two patients with CDEP at Shanghai Children's Hospital were enrolled from July 2014 to January 2018. The forced duction test (FDT) was negative in 21 patients, aged 8mo to 12y (mean 5.4y). Patients were divided into two treatment groups: 16 patients underwent the standard Knapp procedure (group A), with or without horizontal squint procedure; and 5 patients underwent the augmented Knapp procedure (Foster procedure; group B). One patient underwent inferior rectus recession in the affected eye and superior rectus recession in the sound eye because of a positive FDT. The pre- and postoperative vertical deviations in the primary position and ocular motility were compared in the two groups. RESULTS: Twenty-one eyes of the 22 patients (95%) were aligned within 10 prism diopters (PD), and all patients (100%) reached ≥25% elevation improvement after surgery. The average corrected vertical deviation in group B was statistically better than that of group A. For group A, the vertical deviation in the primary position decreased from 24.75Δ±8.35Δ to 4.56Δ±8.07Δ after surgery, for an improvement of 23.06Δ±6.51Δ (P<0.05). In group B, the decrease was from 35.00Δ±5.00Δ (range 30Δ-40Δ) to 1.00Δ±2.24Δ, for an improvement of 34.00Δ±4.18Δ (P<0.05). There were significant differences between the pre- and postoperative elevation in each group (group A, P<0.05; group B, P<0.05). The average scale of improved elevation in group B (1.80±0.45) was not significantly better than that of group A (1.69±0.87; Z=-0.732, P=0.548). The average follow-up periods lasted 21mo in group A and 18mo in group B. CONCLUSION: For vertical deviations <30Δ, the standard Knapp procedure can be chosen. For deviations greater than 30Δ-40Δ, the Foster procedure should be chosen. Because of our early interference, the inferior rectus (IR) muscle did not show mechanical restriction. Monocular elevation deficiency (MED) should be diagnosed early so that complications will be reduced and the procedure will be easier for the surgeon.

[Comparison of sedative effect of dexmedetomidine and midazolam for post-operative patients undergoing mechanical ventilation in surgical intensive care unit].

OBJECTIVE: To study sedative effect and safety of dexmedetomidine and midazolam for post-operative patients undergoing mechanical ventilation(MV) in surgical intensive care unit(SICU). METHODS: Two hundred cases of post-operative patients undergoing MV with tracheal intubation in SICU were enrolled and divided into two groups by random numerical table method. They were treated either with midazolam (98 cases) or dexmedetomidine (102 cases). In both groups fentanyl was given intravenously continually for analgesia. The amount of fentanyl was adjusted according to Prince-Henry analgesic score to keep on 1-2 analgesic score; the dose of sedation was regulated by Riker sedative and restless score (SAS) maintain 2-4 sedative score. During the course, parameters of the ventilator, electrocardiogram, heart rate(HR), blood pressure, respiratory rate, pulse oxygen saturation (SpO(2)), blood gas analysis were observed and registered continuously. The amount of the drug, duration of MV, and incidence of side-effects such as hypotension, bradycardia, delirium, nausea, etc. were recorded in two groups. RESULTS: In all the patients in two groups taking dexmedetomidine or midazolam expected sedative and analgesia scores were obtained. In the group with dexmedetomidine, the patients were aroused easier with adequate sedation, and when compared with the group with midazolam, dose of fentanyl (µg× kg(-1)×h(-1) ) was significantly smaller (0.23±0.13 vs. 0.41±0.12, P<0.01), duration of MV (hours) was clearly shorter (7.20±6.29 vs. 12.44±8.96, P<0.01), the rates of hypotension (27.45% vs. 11.22%) and bradycardia (24.51% vs. 10.20%) were significantly higher (both P<0.05), the rate of delirium was clearly lower (3.92% vs. 31.63%, P<0.01), the rate of nausea showed a slight decrease (9.80% vs. 11.22%, P>0.05). The patients in the group with dexmedetomidine were divided into two subgroups of hypotension and non-hypotension. The quantity of blood loss during operation (ml/kg), amount of fluid infusion during operation (ml× kg(-1)×h(-1) ), blood lactic acid concentration (mmol/L) on the day of surgical operation and the 1st day post-operative showed no significant difference between these subgroups (quantity of blood loss on the day of surgical operation: 12.79±12.13 vs. 13.52±11.62; amount of fluid infusion during surgical operation: 11.91±4.59 vs. 13.09±7.05;blood lactic acid concentration on the day of operation: 1.88±1.07 vs. 1.71±0.87, blood lactic acid concentration on the 1st day post-operative:1.43±0.98 vs. 1.37±0.79, all P>0.05). CONCLUSION: Sedative effect of dexmedetomidine is satisfactory for patients undergoing MV after operation, with the property of easier arousal, lower delirium rate, and it helps to shorten the duration of MV with reduction the dosage of fentanyl by 50%. However, it is necessary to enhance observation in order to prevent and control hypotension and bradycardia.

[Expression of IMP3 in osteosarcoma and its clinical significance].

AIM: To analyze the expressional variability of IMP3 between osteosarcoma and osteochondroma and explore its clinical significance. METHODS: Paraffin sections from 68 patients with osteosarcoma and 20 patients with osteochondroma were examined for the expression of IMP3 by SP immunohistochemistry. RESULTS: The negative, weak positive, moderate positive and strong positive expression rates of IMP3 in 68 patients with osteosarcoma were 4.41% (3/68), 22.06% (15/68), 22.74% (19/68), 45.59% (31/68), respectively, which were significantly higher than those in 20 cases of osteochondroma tissues (P<0.01). The positive expression of IMP3 in osteosarcoma was negative correlation with the 3-year survival rate of osteosarcoma patients after the operation (P<0.01). CONCLUSION: The results suggest that IMP3 plays important roles in the tumorigenesis, progress and prognosis of osteosarcoma, and the expression of IMP3 may be an important feature of osteosarcoma.