Risperidone Induced DNA Methylation Changes in Dopamine Receptor and Stathmin Genes in Mice Exposed to Social Defeat Stress

Objective@#Understanding complex epigenetic mechanisms is necessary to fully elucidate the effects of antipsychotic drug. This study investigated DNA methylation and mRNA expression levels of dopamine D2 and D1 receptor (Drd2 and Drd1, respectively), nuclear receptor subfamily 3, group C, member 1 (Nr3c1) and stathmin 1 (Stmn1) in brain regions of mice exposed to social defeat stress (SDS) and effects of risperidone on altered methylation and mRNA expression levels induced by SDS. @*Methods@#Following SDS for 10 days, risperidone (0.2 mg/kg) or vehicle was administered to adult mice for 7 days. Brain tissues from the prefrontal cortex (PFC), hippocampus (HIP) and amygdala (AMY) were processed to measure methylation and mRNA levels of Drd2, Drd1, Nr3c1 and Stmn1 using pyrosequencing and real time-polymerase chain reaction. @*Results@#We found altered methylation status of Nr3c1 and Stmn1 in the HIP and AMY of mice exposed to SDS. These changes were reversed by risperidone treatment. In addition, different methylation patterns of Drd2 and Drd1 in the PFC and AMY between defeated and control mice were identified with risperidone treatment. @*Conclusion@#These findings suggest that risperidone can cause epigenetic changes in Drd2, Drd1, Nr3c1 and Stmn1 in defeated mice. These changes could be epigenetic mechanisms underlying antipsychotic efficacy.

Impact of Social Defeat Stress on DNA Methylation in Drd2, Nr3c1, and Stmn1 in Wild-type and Stmn1 Knock-out Mice

Objective@#Epigenetic profiles can be modified by stress. Dopamine receptor D2 (Drd2), glucocorticoid receptor gene (Nr3c1) and Stathmin 1 (Stmn1) genes are all implicated in adaptation to stress. The aim of study is to investigate impact of social defeat on DNA methylation in Drd2, Nr3c1, and Stmn1 in wild-type (WT) and Stmn1 knock-out (KO) mice. @*Methods@#The WT and Stmn1 KO mice were subjected to chronic social defeat. Brain tissues of the prefrontal cortex (PFC), amygdala (AMY) and hippocampus (HIP) were obtained. We measured DNA methylation levels of the Drd2, Nr3c1, and Stmn1 genes in the PFC, AMY, and HIP using pyrosequencing. @*Results@#In WT mice, social defeat stress did not induce any changes in Drd2 methylation, whereas significant hypermethylation occurred in Nr3c1 and Stmn1 in the susceptible and unsusceptible groups, respectively, compared to the control group. The methylation responses in the Stmn1 KO mice differed from those seen in the WT mice, such that hypermethylation was evident in all three genes in the susceptible and unsusceptible groups compared to control group. Comparison of the Stmn1 KO and WT mice revealed the same pattern of hypermethylation for all three genes. @*Conclusion@#Social defeat stress induced different epigenetic modifications in three genes among control, unsusceptible, and susceptible groups of WT and Stmn1 KO mice. In particular, hypermethylation of Nr3c1 in the HIP of the susceptible group, and of Stmn1 in the AMY of the unsusceptible group in WT mice, could serve as epigenetic biomarkers of stress susceptibility and stress resilience, respectively.

Clinicopathologic Variables Related to Residual Neoplasia after Cervical Conization / 대한산부인과학회잡지

OBJECTIVE: To evaluate the clinicopathologic variables that are important for predicting residual disease after cervical conization in hysterectomy specimens. METHODS: We performed retrospective review of 125 patients who had undergone cervical conization and endocervical curettage followed by subsequent hysterectomy. Pathologic findings of the cone margins, endocervical curettage samples, and residual lesions in the postcone hysterectomy specimens were recorded for analysis. RESULTS: The prevalence rates of positive cone margins increased with higher severity of cervical neoplasia. There was a statistically significant difference in the prevalence of residual disease in hysterectomy specimens between patients with positive endocervical margins on cone biopsy(67.3%) and those with negative margins(11.8%) (p<0.01). Most residual lesions in the postcone hysterectomy specimens were similar to cone pathology, however the possibility of more advanced lesions in the uterus was present in patients with positive cone margins. Residual disease was significantly more frequently found in patients with positive endocervical curettage(82.4%)(p<0.01). Especially, when both the endocervical margin and endocervical curettage were positive, residual disease was present in 25 of 28 (89.3%) hysterectomy specimens. CONCLUSIONS: From these results, we concluded that the status of endocervical margin and endocervical curettage have significant predictive value with respect to the presence or absence of residual disease, and final decision in regard to subsequent management should be based on histologic finding of the cone margins and endocervical curettage as well as the patient's age and desire to retain reproductive capability.

Hysteroscopic management of intrauterine adhesion and their reproductive outcomes / 대한산부인과학회잡지

One hundred sixty three patients were hysteroscoped for various reasons at our department over 10 year period. Ninety eight patients out of 163 who were diagnosed and treated for their intrauterine adhesions(IUAs) by hysteroscopy were analysed retrospectively. Patients were classified as having mild, moderate or severe stage of IUAs according to American Fertility Society classification. Twenty nine patients(29.6%) had mild IUAs, 43 patients (43.9%) had moderate IUAs, and 26 patients(26.5%) were classified as having severe stage IUAs. The predisposing causal factors of IUAs were abortion, full-term delivery, H. mole, pelvic tuberculosis and myomectomy in order of frequency but in eight cases no cause was identified. After hysteroscopic surgery, although high rate(83.9%) of restoration of normal menstruation was attained but term pregnancy rate was only 53.3% and rather high rate (32%) of preterm or abortion were identified and those pregnancy outcomes were correlated with the stage of IUAs. Complications of surgery consisted of uterine or bladder perforation, pulmonary edema and hemorrhage.

Pathologic Changes in Uterine Leiomyomas Treated by GnRH Agonist Goserelin / 대한산부인과학회잡지

OBJECTIVE: To define the pathologic changes underlying the mechanism of shrinkage of uterine leimyoma in patients treated with goserelin. METHODS: Retrospective evaluation of pathologic changes seen in leiomyoma removed by hysterectomy or myomectomy in treated and untreated patients was done. Microscopic review of all cases was performed without knowledge of the therapeutic history. Each leiomyoma was assessed for hyalinization, hydropic change, lymphocytic infiltrate, nuclear atypia, and hypercellularity. RESULTS: Hyaline degeneration and hydropic changes were found significantly more frequent in patient treated with goserelin (P<0.05). The differences between treated and untreated groups in lymphocytic infiltrate, nuclear atypia, and hypercellularity were not statistically significant. The ultrastructural features of variable numbers of the treated muscle cells showed large vacuole, marked swelling of mitochondria, and compound lysosomal structures presumed to have been formed from damaged intracellular organelles. CONCLUSION: It appears that the rapid decrease in size of the leiomyoma treated with goserein occurs as the smooth muscle tissue undergoes hydropic change and hyaline degeneration. It seems that other cellular degenerative changes may be involved in the mechanism shrinkage of uterine leiomyoma.

The Use of Sonohysterography in Infertile Patients / 대한산부인과학회잡지

OBJECTIVE: The purpose of this study was to assess the usefulness of sonohysterography in the detection of abnormalities of the uterine cavity in infertile patients, compared with other diagnostic methods, such as transvaginal sonography, hysterosalpingography and hysteroscopy. METHODS: Three intrauterine pathologies including intrauterine synechiae, endometrial polyp and submucosal myoma, that could be possible causes of infertility were diagnosed. RESULTS: Transvaginal ultrasonography and hysterosalpingography were able to detect 41.7% and 83.3% of uterine pathologies respectively comparing with sonohysterography to detect all of the uterine pathologies. CONCLUSION: Our results show that sonohysterography is easy, inexpensive, well-tolerated and non-invasive technique with high sensitivity in the detection of uterine pathologies. Therefore the use of sonohysterography for the diagnosis of intrauterine pathologies in infertile patients is highly recommended.