Restraint stress on female mice diminishes the developmental potential of oocytes: roles of chromatin configuration and histone modification in germinal vesicle stage oocytes.

The mechanisms by which restraint stress impairs oocyte developmental potential are unclear. Factors causing differences between the developmental potential of oocytes with surrounded nucleolus (SN) and that of oocytes with nonsurrounded nucleolus (NSN) are not fully characterized. Furthermore, the relationship between increased histone acetylation and methylation and the increased developmental competence in SN oocytes is particularly worth exploring using a system where the SN configuration can be uncoupled (dissociated) from increased histone modifications. In this study, female mice were subjected to restraint for 24 or 48 h or for 23 days before being examined for oocyte chromatin configuration, histone modification, and development in vitro and in vivo. Results showed that restraint for 48 h or 23 days impaired NSN-to-SN transition, histone acetylation and methylation in SN oocytes, and oocyte developmental potential. However, whereas the percentage of stressed SN oocytes returned to normal after a 48-h postrestraint recovery, neither histone acetylation/methylation in SN oocytes nor developmental competence recovered following postrestraint recovery with equine chorionic gonadotropin (eCG) injection. Priming unstressed mice with eCG expedited oocyte histone modification to an early completion. Contrary to the levels of acetylated and methylated histones, the level of phosphorylated H3S10 increased significantly in the stressed SN oocytes. Together, the results suggest that 1) restraint stress impaired oocyte potential with disturbed histone modifications; 2) SN configuration was uncoupled from increased histone acetylation/methylation in the restraint-stressed oocytes; and 3) the developmental potential of SN oocytes is more closely correlated with epigenetic histone modification than with chromatin configuration.

Antioxidant supplementation overcomes the deleterious effects of maternal restraint stress-induced oxidative stress on mouse oocytes.

In this study, using a mouse model, we tested the hypothesis that restraint stress would impair the developmental potential of oocytes by causing oxidative stress and that antioxidant supplementation could overcome the adverse effect of stress-induced oxidative stress. Female mice were subjected to restraint stress for 24 h starting 24 h after equine chorionic gonadotropin injection. At the end of stress exposure, mice were either killed to recover oocytes for in vitro maturation (IVM) or injected with human chorionic gonadotropin and caged with male mice to observe in vivo development. The effect of antioxidants was tested in vitro by adding them to IVM medium or in vivo by maternal injection immediately before restraint stress exposure. Assays carried out to determine total oxidant and antioxidant status, oxidative stress index, and reactive oxygen species (ROS) and glutathione levels indicated that restraint stress increased oxidative stress in mouse serum, ovaries, and oocytes. Whereas the percentage of blastocysts and number of cells per blastocyst decreased significantly in oocytes from restraint-stressed mice, addition of antioxidants to IVM medium significantly improved their blastocyst development. Supplementation of cystine and cysteamine to IVM medium reduced ROS levels and aneuploidy while increasing glutathione synthesis and improving pre- and postimplantation development of oocytes from restraint-stressed mice. Furthermore, injection of the antioxidant epigallocatechin gallate into restraint-stressed mice significantly improved the blastocyst formation and postimplantation development of their oocytes. In conclusion, restraint stress at the oocyte prematuration stage impaired the developmental potential of oocytes by increasing oxidative stress and addition of antioxidants to IVM medium or maternal antioxidant injection overcame the detrimental effect of stress-induced oxidative stress. The data reported herein are helpful when making attempts to increase the chances of a successful outcome in human IVF, because restraint was applied at a stage similar to the FSH stimulation period in a human IVF program.

Fracture liaison services combined with online home nursing care in fragility hip fracture: a comparative effectiveness pilot study.

Fracture liaison service (FLS) is a management system for osteoporotic fractures, its difficulty lies in long-term management. Through this pilot single-center study, we found that FLS combined with an internet-based follow-up service (online home nursing care) can economically and conveniently monitor patients, reduce falls and refractures, and improve care and medication adherence. INTRODUCTION: Among potential e-health platforms, mobile internet encompasses the largest user group of mobile instant messaging software in Asia and offers strong interaction, low cost, and fast speed. The online home nursing care model prevents unnecessary hospital admissions and readmissions. This study aims to explore the effects of a fracture liaison service (FLS) model combined with online home nursing care on patients with fragility hip fracture. METHODS: Patients discharged after November 2020 received FLS care combined with online home nursing care. Patients discharged from May 2020 to November 2020 received only routine discharge guidance and were classified as the control group. The Parker Mobility Score (PMS), Medical Outcomes Study 36-item short-form health survey (MOS SF-36), general medication adherence scale (GMAS), complication rate, and fall/refracture rates were used to evaluate the efficacy of the FLS combined with online home nursing care during the 52-week follow-up period. RESULTS: Eighty-nine patients with complete follow-up information were included in the analysis at the 52-week follow-up. The FLS combined with online home nursing care was associated with improved osteoporosis patient care, including increased medication adherence (64.58% in the control group and 90.24% in the observation group), improved mental quality of life, reduced fall/refracture rate (12.5% and 4.88%, respectively), and reduced rates of bedsores and joint stiffness; however, there was no effect on functional recovery within 1 year. CONCLUSIONS: We recommend the combination of FLS with online home nursing care, considering the local environment, to economically and conveniently monitor patients, reduce falls and refractures, and improve care and medication adherence.

Developmental potential of prepubertal mouse oocytes is compromised due mainly to their impaired synthesis of glutathione.

Although oocytes from prepubertal animals are found less competent than oocytes from adults, the underlying mechanisms are poorly understood. Using the mouse oocyte model, this paper has tested the hypothesis that the developmental potential of prepubertal oocytes is compromised due mainly to their impaired potential for glutathione synthesis. Oocytes from prepubertal and adult mice, primed with or without eCG, were matured in vitro and assessed for glutathione synthesis potential, oxidative stress, Ca(2+) reserves, fertilization and in vitro development potential. In unprimed mice, abilities for glutathione synthesis, activation, male pronuclear formation, blastocyst formation, cortical granule migration and polyspermic block were all compromised significantly in prepubertal compared to adult oocytes. Cysteamine and cystine supplementation to maturation medium significantly promoted oocyte glutathione synthesis and blastocyst development but difference due to maternal age remained. Whereas reactive oxygen species (ROS) levels increased, Ca(2+) storage decreased significantly in prepubertal oocytes. Levels of both catalytic and modifier subunits of the γ-glutamylcysteine ligase were significantly lower in prepubertal than in adult oocytes. Maternal eCG priming improved all the parameters and eliminated the age difference. Together, the results have confirmed our hypothesis by showing that prepubertal oocytes have a decreased ability to synthesize glutathione leading to an impaired potential to reduce ROS and to form male pronuclei and blastocysts. The resulting oxidative stress decreases the intracellular Ca(2+) store resulting in impaired activation at fertilization, and damages the microfilament network, which affects cortical granule redistribution leading to polyspermy.