Downregulation of extracellular matrix and cell adhesion molecules in cumulus cells of infertile polycystic ovary syndrome women with and without insulin resistance

Objective: The extracellular matrix [ECM] of the cumulus oocyte complex [COC] is composed of several molecules that have different roles during follicle development. This study aims to explore gene expression profiles for ECM and cell adhesion molecules in the cumulus cells of polycystic ovary syndrome [PCOS] patients based on their insulin sensitivity following controlled ovarian stimulation [COS]

Materials and Methods: In this prospective case-control study enrolled 23 women less than 36 years of age who participated in an intracytoplasmic sperm injection [ICSI] program. Patients were subdivided into 3 groups: control [n=8, fertile women with male infertility history], insulin resistant [IR] PCOS [n=7], and insulin sensitive [IS] PCOS [n=8]. We compared 84 ECM component and adhesion molecule gene expressions by quantitative real-time polymerase chain reaction array [qPCR-array] among the groups

Results: We noted that 21 of the 84 studied genes differentially expressed among the groups, from which 18 of these genes downregulated. Overall, comparison of PCOS cases with controls showed downregulation of extracellular matrix protein 1 [ECM1]; catenin [cadherin-associated protein], alpha 1 [CTNNA1]; integrin, alpha 5 [ITGA5]; laminin, alpha 3 [LAMA3]; laminin, beta 1 [LAMB1]; fibronectin 1 [FN1]; and integrin, alpha 7 [ITGA7]. In the IS group, there was upregulation of ADAM metallopeptidase with thrombospondin type 1 motif, 8 [ADAMTS8] and neural cell adhesion molecule 1 [NCAM1] compared with the controls [P<0.05]

Conclusion: Downregulation of ECM and cell adhesion molecules seem to be related to PCOS. Gene expression profile alterations in cumulus cells from both the IS and IR groups of PCOS patients seems to be involved in the composition and regulation of ECM during the ovulation process. This study highlights the association of ECM gene alteration as a viewpoint for additional understanding of the etiology of PCOS

Role of 5-HT[1] receptors of accumbens shell arena upon ACPA-induced anxiolytic-like behaviors in rat

Cannabinoids induce diverse responses on anxiolytic-like behaviors. Moreover some studies postulated that there is a close relationship between this system and serotonergic system upon cognitive process formation. Thus the aim of present study is investigation the possible role of 5-HT[1] receptor on anxiolytic-like behaviors induced by ACPA in the elevated plus maze task [EPM]. In the present study rats weighting 250-300g upon surgery bilateral guide cannulae were implanted to allow microinjection of ACPA [agonist CB1 receptor], CP94253 Hcl[agonist 5-HT[1] receptor] alone and them interaction in the AcbSh. The data showed pretest AcbSh infusion of ACPA at doses of0.0002, 0.002, 0.02 and 0.2 micro g/rat increased and decreased the percentage of open-arms time [%OAT] and percentage of Enclosed-arms time [%CAT], respectively as compared to control groups. Pretest AcbSh infusion ofCP94253 Hcl at doses of 5, 0.5 and 0.05 ng/rat, did not alter anxiety-like behaviors. In addition intra-AcbSh microinjection of subthreshold dose of CP94253 Hcl did not alter ACPA-induced anxiolytic-like behaviors. Our data suggest that activation of AcbSh 5-HT[1] receptor did not involve in ACPA-induced behaviors in the EPM task

Intrahippocampal injection of 3 alpha diol [a testosterone metabolite] and indomethacin [3 alpha -HSD blocker], impair acquisition of spatial learning and memory in adult male rats

Hippocampus is essentially involved in learning and memory processes, and is known to be a target for androgen actions. The high density of the androgen receptors in hippocampus shows that there must be some relationship between androgens and memory. Androgen effects on spatial memory are complex and contradictory. Some evidence suggests a positive correlation between androgens and spatial memory. While some other reports indicated an impairment effect. The present study was conducted to assess the effect of 3 alpha diol on spatial discrimination of rats. Adult male rats were bilaterally cannulated into CA1 region of hippocampus and then received 3 alpha diol [0.2, 1, 3 and 6 micro g/ 0.5 micro L/side], indomethacin [1.5, 3 and 6 micro g/ 0.5 micro L/side], indomethacin [3 micro g/ 0.5 micro L/side] + 3 alpha diol [1 micro g/ 0.5 micro L/side], 25-35 min before training in Morris Water Maze task. Our results showed that injection of 3 alpha diol [1, 3 and 6 micro g/ 0.5 micro L/side] and indomethacin [3 and 6 micro g/ 0.5 micro L/side] significantly increased the escape latency and traveled distance to find hidden platform. It is concluded that intra CA1 administration of 3 alpha diol and indomethacin could impair spatial learning and memory in acquisition stage. However, intra hippocampal injection of indomethacin plus 3 alpha diol could not change spatial learning and memory impairment effect of indomethacin or 3 alpha diol in Morris Water Maze task

Role of serotonergic system on modulation of depressogenic-like effects of silymarine

In the present study, we have investigated the effects of silymarine on depression and the possible role of serotonergic system in these effects. The rats were anesthetized intraperitoneally with ketamine hydrochloride and placed in a Stoelting stereotaxic instrument. A stainless steel guide cannula [22-gauge] was implanted in the third ventricular region. The third ventricular region was infused by means of an internal cannula [27-gauge], terminated 1 mm below the tip of the guide cannula. Forced swimming test was used for evaluating the depression. The results obtained from this study showed that oral administration of silymarin [35, 70, 140 and 280 mg/rat] for two weeks increased the immobility time in forced swimming test, indicating an increase in depression level of the treated rats. Intra-third-ventricle [Intra-TV] infusion of 5HT1A receptor agonist 8-OH-DPAT [25 and 10 ng/rat] decreased the immobility time indicating an anti-depression effect, while injection of 5HT1A receptor antagonist NAN190 [0.25, 0.5 and 1 microg/rat] had no significant effect on immobility time. An effective dose of 8-OH-DPAT [10 ng/rat] co-administered with silymarin [140 and 280 mg/rat] decreased the depressogenic effects of silymarin. These results showed that the depressogenic effects of silymarin may be modulated via 5HT1A receptor of serotonin

Cytotoxic effects of essential oils of some Iranian citrus peels

There have been efforts to overcome the problem in treatment of cancer using medicinal plants. It has been shown that Citrus essential oil of contains different terpens with antitumor activities. In this study we sought to determine the cytotoxicity of essential oils of Iranian Citrus limon [L.], C. medica [L.], C. sinsensis [L.] peels on cancer cell lines. Essential oils were prepared by hydrodistilation and characterized by GC-MS. The effects of C. limon [5-40 micro g/ml], C. medica and C. sinensis [0.25-10 micro g/ml] on two human tumor cell lines [MCF-7 and Hela] were determined. Different concentrations of essential oils were added to cultured cells and incubated for 72 h. Cell survival was evaluated using the MTT-based cytotoxicity assay. While limonene comprise about 98.4% and 98.8% of content of C. limon and C. sinensis essential oils respectively, its' percentage in C. medica was only 56.6%. In C. medica there was a considerable amount of beta-pinene, gamma-terpinene, alpha-terpinolene and trans-alpha-bergamotene. IC[50] of essential oil for MCF-7 cell line was: C. limon almost equal to 10 micro g/ml, C. medica almost equal to 1 micro g/ml and C. sinensis almost equal to 0.5 micro g/ml. For Hela cell line IC50 was: C. limon almost equal to 17 micro g/ml, C. medica almost equal to 1 micro g/ml and C. sinensis almost equal to 3 micro g/ml. Our findings revealed that C. limon and C. sinensis had a greater cytotoxic effect on MCF-7 than that on Hela cells. Also, comparing IC50, our findings indicated that C. medica and C. sinensis were more cytotoxic than C. limon. Comparison of the essential oil component of C. limon with C. medica, shows the presence of beta-pinene [16.3%], alpha-terpineol [11.3%], gamma-terpinene [4.4%], and trans- alpha-bergamotene [3.4%], which were not found in C. limon. Hence, it could be concluded that these components may have greater cytotoxic effects or they may also have synergistic effects with limonene