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Sample records for rat ovary interactions

  1. Cryopreservation and orthotopic transplantation of rat ovaries.

    PubMed

    Dorsch, Martina; Wedekind, Dirk

    2010-01-01

    The number of rat strains increased considerably in the last decade and will increase continuously during the next years. This requires enough space for maintaining vital strains and techniques for cryobanking, which can be applied not only in specialised rat resource centres but also in regular animal houses. Here we describe an easy and fast method for the cryopreservation and transplantation of frozen-thawed ovaries of the rat. With dimethyl sulfoxide as cryoprotectant rat ovaries can be stored at -196 degrees C for unlimited time. For revitalisation thawed ovaries have to be orthotopically transplanted into appropriate ovarectomised recipients. Reestablishment of the reproductive cycle in the recipients can be confirmed by vaginal cytology shortly after transplantation. The recipients are able to produce 2-3 litters after mating with males of an appropriate strain. Cyropreservation of ovaries thus can be considered a reliable method to preserve scientifically and economically important stocks and strains of rats that are currently not required. PMID:20013242

  2. Circulating hormone concentrations in hypothyroid rats with induced polycystic ovaries.

    PubMed

    Lee, M T; Adams, W C; Bruot, B C

    1991-11-01

    The induction of polycystic ovaries in hypothyroid rats by human chorionic gonadotropin (hCG) has been studied for many years. A complete understanding of this phenomenon requires information regarding the circulating levels of the hormones of the hypophyseal-gonadal axis. In this study, serum prolactin (PRL), luteinizing hormone (LH), estradiol, testosterone, and progesterone were measured by radioimmunoassay at intervals during the 40-day period in which large ovarian cysts were induced in hypothyroid rats by daily injections of hCG. After 20 injections, ovaries increased in weight 10-fold, and well-developed ovarian cysts were present, accompanied by lutein tissue; cyst development continued for the subsequent 20 days of hCG. Both PRL and LH rose during the first 5 days of treatment and were maintained at high levels from day 20 on. The pattern of change of gonadal steroids showed greater increases with hCG in hypothyroid than in euthyroid rats. Levels of estradiol in hypothyroid, hCG-injected rats increased in parallel to ovarian hypertrophy, whereas progesterone was high in initial stages and then declined. Testosterone increased in both euthyroid and hypothyroid animals, with no clear pattern coincident with cyst formation. The data suggest that the formation of polycystic ovaries in the hypothyroid rat is associated with high levels of PRL and LH followed by elevations of estradiol, which may serve to maintain continuous PRL, as well as LH, stimulation of the ovary. PMID:1924408

  3. Dehydroepiandrosterone-induced polycystic ovaries and acyclicity in the rat.

    PubMed

    Knudsen, J F; Costoff, A; Mahesh, V B

    1975-08-01

    Administration of dehydroepiandrosterone (DHA) to the immature female rat resulted in one precocious ovulation followed by ovulatory failure. The animals exhibited either "constant-estrus" or "constant-diestrus" vaginal smears, and the ovaries were either polycystic or contained corpus luteum-like structures. Serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels showed an ovulatory type surge on day 30, at the time of the precocious ovulation. Thereafter, serum FSH levels were comparable to those of control rats, whereas the LH levels were very low. Serum prolactin was elevated significantly in DHA-treated animals. The ovaries of DHA-treated animals were responsive to gonadotropins and the pituitary was responsive to luteinizing hormone-releasing hormone. Withdrawal of androgen treatment resulted in restoration of cyclicity. This animal model demonstrates that an androgen insult can cause ovulatory failure and polycystic ovaries in spite of normal ovaries, adrenals, and hypothalamic-pituitary mechanisms. That such ovulatory failure is a result of the androgen administration is further substantiated by restoration of cyclicity after androgen withdrawal. This animal model in several ways is similar to the human polycystic ovary syndrome and has a potential application in the study of the mechanism of androgen-induced ovulatory failure. PMID:125663

  4. Downregulation of natriuretic peptide system and increased steroidogenesis in rat polycystic ovary.

    PubMed

    Pereira, Virginia M; Honorato-Sampaio, Kinulpe; Martins, Almir S; Reis, Fernando M; Reis, Adelina M

    2014-10-01

    Atrial natriuretic peptide (ANP) is known to regulate ovarian functions, such as follicular growth and steroid hormone production. The aim of the present study was to investigate the natriuretic peptide system in a rat model of chronic anovulation, the rat polycystic ovary. Adult female Wistar rats received a single subcutaneous injection of 2mg estradiol valerate to induce polycystic ovaries, while the control group received vehicle injection. Two months later, their ovaries were quickly removed and analyzed. Polycystic ovaries exhibited marked elevation of testosterone and estradiol levels compared to control ovaries. The levels of ANP and the expression of ANP mRNA were highly reduced in the polycystic ovaries compared to controls. By immunohistochemistry, polycystic ovaries showed weaker ANP staining in stroma, theca cells and oocytes compared to controls. Polycystic ovaries also had increased activity of neutral endopeptidase, the main proteolytic enzyme that degrades natriuretic peptides. ANP receptor C mRNA was reduced and ANP binding to this receptor was absent in polycystic ovaries. Collectively, these results indicate a downregulation of the natriuretic peptide system in rat polycystic ovary, an established experimental model of anovulation with high ovarian testosterone and estradiol levels. Together with previous evidence demonstrating that ANP inhibits ovarian steroidogenesis, these findings suggest that low ovarian ANP levels may contribute to the abnormal steroid hormone balance in polycystic ovaries. PMID:25111374

  5. Development of mouse and rat oocytes in chimeric reaggregated ovaries after interspecific exchange of somatic and germ cell components.

    PubMed

    Eppig, J J; Wigglesworth, K

    2000-10-01

    The germ cell and somatic cell compartments of newborn rat and mouse ovaries, which contain only primordial stage follicles, were completely exchanged and reaggregated to produce xenogeneic chimeric ovaries. The reaggregated ovaries were grafted beneath the renal capsules of ovariectomized SCID mice to develop for periods up to 21 days. Xenogeneic follicles developed with essentially normal morphological characteristics. Both rat and mouse oocytes with species-specific characteristics grew within follicles that were composed of somatic cells exclusively of the alternative species. Rat oocytes grown in mouse follicles became competent to resume meiosis, and progressed to metaphase II when they were removed from follicles and cultured. In addition, mouse oocytes grown in rat follicles underwent fertilization and preimplantation development in vitro, and developed to term after embryos were transferred to pseudopregnant mouse foster mothers. Therefore, despite an estimated 11 million years of divergent evolution, oocytes and somatic cells of rat and mouse ovaries can be exchanged and can produce functional oocytes. It is concluded that factors involved in oocyte-somatic cell interactions necessary to support oocyte development and appropriate differentiation of the oocyte-associated granulosa cells are conserved between rats and mice. Moreover, although granulosa cells play important roles in oocyte development, the development of species-specific characteristics of oocytes occurs without apparent modification by a xenogeneic follicular environment. PMID:10993822

  6. Trichloroethylene Metabolism in the Rat Ovary Reduces Oocyte Fertilizability

    PubMed Central

    Wu, Katherine Lily; Berger, Trish

    2007-01-01

    Exposure to trichloroethylene (TCE, an environmental toxicant) reduced oocyte fertilizability in the rat. In vivo, TCE may be metabolized by cytochrome P450 dependent oxidation or glutathione conjugation in the liver or kidneys, respectively. Cytochrome P450 dependent oxidation is the higher affinity pathway. The primary isoform of cytochrome P450 to metabolize TCE in the liver, cytochrome P450 2E1, is present in the rodent ovary. Ovarian metabolism of TCE by the oxidative pathway and the production of reactive oxygen species may occur given the presence of the metabolizing enzyme. The objectives of this study were to define the sensitive interval of oocyte growth to TCE exposure, and to determine if TCE exposure resulted in the formation of ovarian protein carbonyls, an indicator of oxidative damage. Rats were exposed to TCE in drinking water (0.45% TCE (v/v) in 3% Tween) or 3% Tween (vehicle-control) during three 4–5 day intervals of oocyte development preceding ovulation. Oocytes from TCE-exposed females were less fertilizable compared with vehicle-control oocytes. Immunohistochemical labeling of ovaries and Western blotting of ovarian proteins demonstrated TCE treatment induced a greater incidence of protein carbonyls compared with vehicle controls. Protein carbonyl formation in the ovary is consistent with TCE metabolism by the cytochrome P450 pathway. Oxidative damage following ovarian TCE metabolism or the presence of TCE metabolites may contribute to reduced oocyte fertilizability. In summary, these results indicate maturing oocytes are susceptible to very short in vivo exposures to TCE. PMID:17673192

  7. Heart Rate Changes in Electroacupuncture Treated Polycystic Ovary in Rats

    PubMed Central

    Ramadoss, Mukilan; Subbiah, Angelie Jessica; Natrajan, Chidambaranathan

    2016-01-01

    Introduction Polycystic Ovary Syndrome (PCOS) is a common metabolic disorder, it affects both humans and animals. It may induce coronary heart disease, obesity and hyperandrogenism. Previous studies show that Low frequency Electroacupuncture (EA) have an effect on PCOS, however the exact pathway is unclear. Aim To find the effect of EA on autonomic activity of the heart in Estradiol Valerate (EV) induced PCOS rats. Materials and Methods Heart rate variability (HRV) was assessed in 3 groups: 1) Control; 2) PCOS rats; and 3) PCOS rats after EA treatment (n=8 in each group). From the time domain analysis and frequency domain analysis (linear measures) HRV analysis was done. EA stimulation was given at low frequency of 2Hz for 15 min on alternate days for 4-5 weeks. Collected data were statistically analysed using One-Way Analysis of Variance with the application of multiple comparisons of Tukey test. Results EA treatment group shows significant reduction in Heart Rate (HR) and low frequency, high frequency ratio (LF/HF); and increase in RR interval, Total Power (TP) when compared to PCOS group. Conclusion The study concludes that EA treatment has a significant effect on reducing sympathetic tone and decreasing HR in PCOS. PMID:27134868

  8. Expression of SIRT1 in the ovaries of rats with polycystic ovary syndrome before and after therapeutic intervention with exenatide

    PubMed Central

    Tao, Xin; Zhang, Xiao; Ge, Shu-Qi; Zhang, Er-Hong; Zhang, Bin

    2015-01-01

    Aim: To investigate the expression of silent information regulator 1 (SIRT1) in rats with polycystic ovary syndrome (PCOS) and its alteration after exenatide treatment. Methods: PCOS rat model was established by dehydroepiandrosterone induction. The animals were randomly divided into exenatide treatment group (EX group, n = 10), metformin treatment group (MF group, n = 10), PCOS group (PCOS group, n = 9) and normal control group (NC group, n = 10). Histological changes of the ovarian tissues were examined by HE staining. SIRT1 expression in the ovarian tissue was detected by RT-PCR and immunohistochemistry. Results: Rats in the PCOS group lost their estrous cycle. Histological observation of the ovary showed saccular dilatation of the follicle, decreased number of corpora lutea, fewer layers of granulosa cells aligned loosely, and thickened layer of theca cells. The changes in reproductive hormones and the development of insulin resistance suggested the successful establishment of the animal models. Immunohistochemistry and Q-PCR detected the mRNA and protein expressions of SIRT1 in the ovary tissues of rats in the normal control group. The SIRT1 expression was significantly lower in PCOS group than in control group (P < 0.05); after drug intervention, the SIRT1 expression significantly increased in EX and MF groups (compared with the PCOS group), whereas no significant difference was noted between the EX group and MF group. Conclusions: The SIRT1 expression in the ovary tissue decreases in PCOS rats (compare with the normal rats) but can be up-regulated after Ex or MF treatment. These drugs may affect the process and development of PCOS by regulating the SIRT1 expression. Exenatide may be therapeutic for PCOS by up-regulating the SITR1 expression. PMID:26339397

  9. Differential Expression of microRNAs in the Ovaries from Letrozole-Induced Rat Model of Polycystic Ovary Syndrome.

    PubMed

    Li, Dandan; Li, Chunjin; Xu, Ying; Xu, Duo; Li, Hongjiao; Gao, Liwei; Chen, Shuxiong; Fu, Lulu; Xu, Xin; Liu, Yongzheng; Zhang, Xueying; Zhang, Jingshun; Ming, Hao; Zheng, Lianwen

    2016-04-01

    Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disorder. To understand the pathogenesis of PCOS, we established rat models of PCOS induced by letrozole and employed deep sequencing to screen the differential expression of microRNAs (miRNAs) in PCOS rats and control rats. We observed vaginal smear and detected ovarian pathological alteration and hormone level changes in PCOS rats. Deep sequencing showed that a total of 129 miRNAs were differentially expressed in the ovaries from letrozole-induced rat model compared with the control, including 49 miRNAs upregulated and 80 miRNAs downregulated. Furthermore, the differential expression of miR-201-5p, miR-34b-5p, miR-141-3p, and miR-200a-3p were confirmed by real-time polymerase chain reaction. Bioinformatic analysis revealed that these four miRNAs were predicted to target a large set of genes with different functions. Pathway analysis supported that the miRNAs regulate oocyte meiosis, mitogen-activated protein kinase (MAPK) signaling, phosphoinositide 3-kinase/Akt (PI3K-Akt) signaling, Rap1 signaling, and Notch signaling. These data indicate that miRNAs are differentially expressed in rat PCOS model and the differentially expressed miRNA are involved in the etiology and pathophysiology of PCOS. Our findings will help identify miRNAs as novel diagnostic markers and therapeutic targets for PCOS. PMID:26745201

  10. Hyberbaric oxygen increases atresia in normal & steroid induced PCO rat ovaries

    PubMed Central

    2012-01-01

    Background In this study, we investigated the effect of hyperbaric oxygen therapy (HBOT) on the morphology of estradiol valerate (EV) induced polycystic ovary (PCO) to find a new treatment modality for improvement of PCO. Methods The rats were divided into four groups. Group1, control; group 2, PCO group; group 3, PCO with HBOT group and group 4, normal ovary with HBOT. PCO was induced by a single intramuscular injection of 4 mg EV in adult cycling rats. Other rats with normal ovaries had oil injection as placebo. HBOT was applied to third and fourth groups for six weeks. Histopathologic evaluation of ovaries of all groups were performed & compared. Results Six weeks of HBOT was resulted in increase in follicular atresia, decrease in the number of primary, secondary, tertiary follicles and decrease in the number of fresh corpus luteum in normal rat ovary. HBOT on polycystic rat ovary, resulted in significant increase in atretic follicles which were already present. Conclusions HBOT of six weeks itself, changed ovarian morphology in favor of atresia both in PCO group and control group. This result of aggravated follicular atresia after HBOT on EV induced PCO may be due to long-term exposure in our protocol which with this state seems to be inapplicable in the improvement of PCO morphology. PMID:22309835

  11. Regulation of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase expression and activity in the hypophysectomized rat ovary: Interactions between the stimulatory effect of human chorionic gonadotropin and the luteolytic effect of prolactin

    SciTech Connect

    Martel, C.; Labrie, C.; Dupont, E.; Couet, J.; Trudel, C.; Rheaume, E.; Simard, J.; Luu-The, V.; Pelletier, G.; Labrie, F. )

    1990-12-01

    The enzyme 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) catalyzes an obligatory step in the conversion of pregnenolone and other 5-ene-3 beta-hydroxysteroids into progesterone as well as precursors of all androgens and estrogens in the ovary. Since 3 beta-HSD is likely to be an important target for regulation by pituitary hormones, we have studied the effect of chronic treatment with LH (hCG), FSH, and PRL on ovarian 3 beta-HSD expression and activity in hypophysectomized adult female rats. Human CG (hCG) (10 IU, twice a day (bid)), ovine FSH (0.5 microgram, bid), and ovine PRL (1 mg, bid) were administered, singly or in combination, for a period of 10 days starting 15 days after hypophysectomy. In hypophysectomized rats, PRL exerted a potent inhibitory effect on all the parameters studied. In fact, PRL caused a 81% decrease in ovarian 3 beta-HSD mRNA content accompanied by a similar decrease in 3 beta-HSD activity and protein levels. In addition, ovarian weight decreased by 40% whereas serum progesterone fell dramatically from 1.92 nmol/liter to undetectable levels after treatment with PRL. Whereas hCG alone had only slight stimulatory effects on 3 beta-HSD mRNA, protein content and activity levels, treatment with the gonadotropin partially or completely reversed the potent inhibitory effects of oPRL on all the parameters measured. FSH, on the other hand, had no significant effect on 3 beta-HSD expression and activity. In situ hybridization experiments using the 35S-labeled rat ovary 3 beta-HSD cDNA probe show that the inhibitory effect of PRL is exerted primarily on luteal cell 3 beta-HSD expression and activity. On the other hand, it can be seen that hCG stimulates 3 beta-HSD mRNA accumulation in interstitial cells.

  12. Stereological study of the effects of letrozole and estradiol valerate treatment on the ovary of rats

    PubMed Central

    Noorafshan, Ali; Ahmadi, Maryam; Mesbah, Seyed-Fakhroddin

    2013-01-01

    Objective Letrozole and estradiol valerate are used to treat some hormonally-responsive symptoms and also in modeling of the polycystic ovary syndrome. However, the stereological analysis of the ovary has received less attention. Estimation of the whole ovary volume using the Cavalieri method can be applied in any orientation desired, but estimation of the mean volume of the oocytes requires isotropic uniform random sectioning. Here, a combined method was developed for estimating the parameters. To our knowledge, no comparison has been made of the effects of letrozole and estradiol on the ovary. Methods Sixty rats were divided into 4 groups receiving estradiol (4 mg/kg), olive oil, letrozole (1 mg/kg), or normal saline. After 21 days, their ovaries were studied. Results Relative to the control group, the total volume of the ovary and the cortex increased in the letrozole-treated and estradiol-treated rats. In addition, the number of the preantral, antral, and granulosa cells decreased by 43% to 56% in the letrozole- and estradiol-treated rats. On average, a 19% increase was observed in the atretic oocytes of the letrozole-treated and estradiol-treated rats, but the mean oocyte volume decreased by 29% to 44% in letrozole- and estradiol-treated rats. Furthermore, the letrozole-treated rats showed a 5-fold and 7-fold increase in the volume of the cysts and corpus luteum, respectively. A 3-fold increase was found in the volume of both the cysts and corpus luteum in the estradiol group. Conclusion The structural changes of the ovary were most pronounced in the letrozole-treated animals. PMID:24179868

  13. Tributyltin increases the expression of apoptosis- and adipogenesis-related genes in rat ovaries

    PubMed Central

    Lee, Hyojin; Lim, Sojeong; Yun, Sujin; Yoon, Ayoung; Park, Gayoung

    2012-01-01

    Objective Tributyltin (TBT), an endocrine disrupting chemical, has been reported to decrease ovarian function by causing apoptosis in the ovary, but the mechanism is not fully understood. Therefore, we examined whether TBT increases the expression of adipogenesis-related genes in the ovary and the increased expression of these genes is associated with apoptosis induction. Methods Three-week-old Sprague-Dawley rats were orally administered TBT (1 or 10 mg/kg body weight) or sesame oil as a control for 7 days. The ovaries were obtained and weighed on day 8, and then they were fixed for terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) or frozen for RNA extraction. Using the total RNA of the ovaries, adipogenesis- and apoptosis-related genes were analyzed by real-time polymerase chain reaction (PCR). Results The ovarian weight was significantly decreased in rats administered 10 mg/kg TBT compared to that in control rats. As determined by the TUNEL assay, the number of apoptotic follicles in ovary was significantly increased in rats administered 10 mg/kg TBT. The real-time PCR results showed that the expression of adipogenesis-related genes such as PPARγ, aP2, CD36, and PEPCK was increased after TBT administration. In addition, apoptosis-related genes such as TNFα and TNFR1 were expressed more in the TBT-administered rats compared with the control rats. Conclusion The present study demonstrates that TBT induces the expression of adipogenesis- and apoptosis-related genes in the ovary leading to apoptosis in the ovarian follicles. These results suggest that the increased expression of adipogenesis-related genes in the ovary by TBT exposure might induce apoptosis resulting in a loss of ovarian function. PMID:22563546

  14. Lateralization of the connections of the ovary to the celiac ganglia in juvenile rats

    PubMed Central

    Morán, Carolina; Zarate, Fabiola; Morán, José Luis; Handal, Anabella; Domínguez, Roberto

    2009-01-01

    During the development of the female rat, a maturing process of the factors that regulate the functioning of the ovaries takes place, resulting in different responses according to the age of the animal. Studies show that peripheral innervation is one relevant factor involved. In the present study we analyzed the anatomical relationship between the neurons in the celiac-superior mesenteric ganglia (CSMG), and the right or left ovary in 24 or 28 days old female pre-pubertal rats. The participation of the superior ovarian nerve (SON) in the communication between the CSMG and the ovaries was analyzed in animals with unilateral section of the SON, previous to injecting true blue (TB) into the ovarian bursa. The animals were killed seven days after treatment. TB stained neurons were quantified at the superior mesenteric-celiac ganglia. The number of labeled neurons in the CSMG of rats treated at 28 days of age was significantly higher than those treated on day 24. At age 24 days, injecting TB into the right ovary resulted in neuron stains on both sides of the celiac ganglia; whereas, injecting the left side the stains were exclusively ipsilateral. Such asymmetry was not observed when the rats were treated at age of 28 days. In younger rats, sectioning the left SON resulted in significantly lower number of stained neurons in the left ganglia while sectioning the right SON did not modify the number of stained neurons. When sectioning of the SON was performed to 28 days old rats, no staining was observed. Present results show that the number and connectivity of post-ganglionic neurons of the CSMG connected to the ovary of juvenile female rats change as the animal mature; that the SON plays a role in this communication process as puberty approaches; and that this maturing process is different for the right or the left ovary. PMID:19460167

  15. Histological evaluation of rat larynx in experimental polycystic ovary syndrome model.

    PubMed

    Deveci, Hande Senem; Deveci, Ildem; Habesoglu, Mehmet; Sürmeli, Mehmet; Kınıs, Vefa; Eriman, Murat; Gunes, Pembegul; Yekrek, Murat; Egeli, Erol

    2012-08-01

    This study aimed at studying the histopathological effects of hyperandrogenemia and estrogen deficiency on larynx mucosa in experimentally designed polycystic ovary syndrome of female rats. Two groups of experimental polycystic ovary syndrome model were composed in healthy female rats by per oral letrozole administration of for 21 and 42 days. Also a control group which only took vehicle (saline) for 42 days was designed. Laryngeal mucosa and ovaries of all animals were examined histopathologically by light microscopy and the serum hormone levels were analyzed using a solid-phase, two-site chemiluminescent enzyme immunometric assay. Statistically significant edema, vascular engorgement, inflammation, cilia loss and differentiation of goblet cell distribution were observed when the control group and study groups were compared (p < 0.01). In serum hormonal analysis there was a significant increase in levels of androgens and decrease in levels of estrogens. In addition, polycystic appearance of ovaries in letrozole-administered groups and normal appearance of ovaries in control group have been proven histopathologically. Polycystic ovary syndrome which causes estrogen deficiency and hyperandrogenemia in fertile ages resulted in histopathological changes in laryngeal mucosa. PMID:22407189

  16. Unilateral or bilateral vagotomy induces ovulation in both ovaries of rats with polycystic ovarian syndrome

    PubMed Central

    2013-01-01

    Background Injecting estradiol valerate (EV) to pre-pubertal or adult female rat results in effects similar to those observed in women with polycystic ovarian syndrome (PCOS). One of the mechanisms involved in PCOS development is the hyperactivity of the sympathetic nervous system. In EV-induced PCOS rats, the unilateral sectioning of the superior ovarian nerve (SON) restores ovulation of the innervated ovary. This suggests that, in addition to the sympathetic innervation, other neural mechanisms are involved in the development/maintenance of PCOS. The aims of present study were analyze if the vagus nerve is one of the neural pathways participating in PCOS development. Methods Ten-day old rats were injected with EV dissolved in corn oil. At 24-days of age sham-surgery, unilateral, or bilateral sectioning of the vagus nerve (vagotomy) was performed on these rats. The animals were sacrificed at 90–92 days of age, when they presented vaginal estrous preceded by a pro-estrus smear. Results In EV-induced PCOS rats, unilateral or bilateral vagotomy restored ovulation in both ovaries. Follicle-stimulating hormone (FSH) levels in PCOS rats with unilateral or bilateral vagotomy were lower than in control rats. Conclusions This result suggests that in EV-induced PCOS rats the vagus nerve is a neural pathway participating in maintaining PCOS. The vagus nerve innervates the ovaries directly and indirectly through its synapsis in the celiac-superior-mesenteric ganglion, where the somas of neurons originating in the SON are located. Then, it is possible that vagotomy effects in EV-induced PCOS rats may be explained as a lack of communication between the central nervous system and the ovaries. PMID:23866168

  17. A neuroimmune regulation at peripheral level on the steroidogenesis of polycystic ovary in rats.

    PubMed

    Forneris, M L; Aguado, L I; Oliveros, L B

    2003-09-01

    It is known that noradrenergic sympathetic nerve fibers connect the ovary and the spleen from the celiac ganglion. The modulation of the ovarian steroidogenesis in rats with polycystic ovary (PCO) by secretions of culture splenocytes from control (non PCO), PCO and PCO rats with superior ovarian nerve transection (PCO+SON-t) is investigated. Splenocytes from PCO rats increased progesterone (P) and decreasing estradiol (E) and androstenedione (A) release, a steroidogenic response different from that obtained with splenocytes of control rats. PCO also decreased the number of splenocyte beta-adrenergic receptors (betaR). SON transection reverted the effect of PCO on splenocytes betaR numbers and secretions of these splenocytes also reverted the stimulatory effect of PCO on P release, while norepinephrine (NE) treatment to PCO+SON-t splenocytes decreased their betaR number and their secretions restored the stimulation on progesterone release. Inversely, PCO+SON-t splenocyte secretions intensified the inhibition in estradiol with no effect on A. Treatment of PCO+SON-t splenocytes with NE or neuropeptide Y partially reverted the effects of PCO and SON-t The P and E-A response of PCO ovary might be differentially regulated by the splenocyte secretions through the neural connection involving ovary, SON, celiac ganglion and spleen and the neurotransmitter NE. PMID:14656055

  18. Evidence that FOXO3a is involved in oocyte apoptosis in the neonatal rat ovary.

    PubMed

    Sui, Xu-Xia; Luo, Li-Li; Xu, Jin-Jie; Fu, Yu-Cai

    2010-08-01

    Previous studies have proposed that the forkhead transcription factor FOXO3a is involved in cell cycle arrest and apoptosis and that it may also repress follicular development by inducing cell cycle arrest in ovaries. We have recently demonstrated that FOXO3a induces oocyte apoptosis of neonatal rat ovaries under in vitro conditions. In the present study, we evaluated the role of FOXO3a in oocyte apoptosis under in vivo conditions. Ovaries from rats were obtained from newborns on postnatal day (PD) 1, 2, 3, and 4. TUNEL assay results showed that oocyte apoptosis occurred mainly on PD 1 and 2. Immunohistochemical staining of FOXO3a, Bim, Fas ligand (FasL), p27KIP1, caspase-8, and caspase-3 showed that they were all expressed mainly in naked oocytes on PD 1 and 2. The percentage of positive FOXO3a staining of oocytes reached peak levels in the ovaries of 2-day-old rats, which was consistent with the rate of the apoptotic profiles determined by TUNEL. The percentage between TUNEL-positive and FOXO3a-positive oocytes in the nucleus showed no statistical differences within the 4-day-old rat ovaries. Furthermore, the positive oocyte percentage of the target factors of FOXO3a (Bim, p27KIP1, and FasL) and pro-apoptotic proteins (caspase-3 and caspase-8) also reached peak levels in the ovaries of 2-day-old rats, which was similar to the rate of FOXO3a-positive oocytes. These results suggest that FOXO3a in the oocyte nucleus is involved in oocyte apoptosis; that is, FOXO3a-positive oocytes may be the apoptotic cells. To verify this, rat oocytes were subjected to TUNEL and immunofluorescent double-labeling assays. We found that TUNEL-positive cells were also FOXO3a-, Bim-, or FasL-positive. To identify the downstream target of FOXO3a, double immunofluorescent staining with antibodies to Bim and FasL was performed. We found that FOXO3a-positive cells were also Bim- and FasL-positive. We conclude that the overexpression of FOXO3a in the oocyte nucleus of neonatal rat ovaries

  19. Role of macrophage secretions on rat polycystic ovary: its effect on apoptosis.

    PubMed

    Figueroa, Florencia; Motta, Alicia; Acosta, Mariano; Mohamed, Fabian; Oliveros, Liliana; Forneris, Myriam

    2015-11-01

    Polycystic ovarian syndrome is the most common endocrine disorder among women of reproductive age. Little is known about its etiology, although the evidence suggests an intrinsic ovarian abnormality in which endocrine, metabolic, neural and immune factors would be involved. In this work, the effects of macrophage (MO) secretion on ovarian apoptosis in a polycystic ovary syndrome rat model (PCO rat) induced by estradiol valerate are studied. Spleen MO secretions were used to stimulate ovaries and ovarian interstitial and granulosa cells from both PCO and control rats. Ovarian hormones and prostaglandin E2 (PGE2) were measured by RIA; ovarian mRNA levels of Bax, Bcl2 and NFkB by RT-PCR; and ovarian inducible nitric oxide synthase (iNOS) by western blot. The number of apoptotic cells was evaluated by TUNEL. In the PCO ovary, the MO secretions from PCO rats increased the Bax and NFkB mRNA expressions and increased TUNEL staining in both granulosa and theca cells. In addition, the PCO MO secretions produced a decrease of nitric oxide release, iNOS protein level and PGE2 content in the PCO ovary, and it also induced an increase of androstenedione production by PCO interstitial cells, in comparison with control MO secretions. Considering these results and knowing that testosterone stimulates tumour necrosis factor-α production by PCO MO modifying ovarian response by increasing androstenedione, it is reasonable to suggest that the increase of androgens stimulated in ovarian cells by PCO MO secretions could in turn stimulate the cytokine production from MO, thus maintaining an apoptotic vicious cycle in the PCO ovary. PMID:26264225

  20. The effect of gonadotropin on glucose transport and apoptosis in rat ovary.

    PubMed

    Zhang, Cheng; Niu, Wanbao; Wang, Zhengpin; Wang, Xiaoxia; Xia, Guoliang

    2012-01-01

    Although the effects of Gonadotropin on ovarian physiology have been known for many decades, its action on glucose uptake in the rat ovary remained poorly understood. Evidence also suggests that glucose uptake is mediated by a number of glucose transporter proteins (Glut). Therefore, we examined the rat ovary for the presence of Glut1-4 and blood glucose level after eCG (equine chorionic gonadotropin) and anti-eCG antiserum treatment. All of the glucose transports were present in the ovarian oocyte, granulosa cells and theca cells in different stage follicles. The expression of Glut in ovary was up-regulated by eCG, however, anti-eCG antiserum reversed eCG action. Western blot analysis also demonstrated the content of Glut1 was higher in eCG treatment group compared with anti-eCG antiserum and control group. The same tendency was shown in other glut isoforms. Moreover, there were no significant difference between the anti-eCG antiserum and control group. In additional, the level of serum glucose in eCG treatment group was significantly higher than others, which is similar with glut expression pattern. High glucose level in blood is correlated with increased expression of glucose transporter proteins in rat ovary. Meanwhile, anti-eCG antiserum increased granulosa cell apoptosis in antral follicle compared with those in eCG group. Our observations provide potential explanation for the effects of Glut on follicular development in rat ovary and a role for eCG in the regulation of ovarian glucose uptake. PMID:22870326

  1. The Effect of Gonadotropin on Glucose Transport and Apoptosis in Rat Ovary

    PubMed Central

    Zhang, Cheng; Niu, Wanbao; Wang, Zhengpin; Wang, Xiaoxia; Xia, Guoliang

    2012-01-01

    Although the effects of Gonadotropin on ovarian physiology have been known for many decades, its action on glucose uptake in the rat ovary remained poorly understood. Evidence also suggests that glucose uptake is mediated by a number of glucose transporter proteins (Glut). Therefore, we examined the rat ovary for the presence of Glut1–4 and blood glucose level after eCG (equine chorionic gonadotropin) and anti-eCG antiserum treatment. All of the glucose transports were present in the ovarian oocyte, granulosa cells and theca cells in different stage follicles. The expression of Glut in ovary was up-regulated by eCG, however, anti-eCG antiserum reversed eCG action. Western blot analysis also demonstrated the content of Glut1 was higher in eCG treatment group compared with anti-eCG antiserum and control group. The same tendency was shown in other glut isoforms. Moreover, there were no significant difference between the anti-eCG antiserum and control group. In additional, the level of serum glucose in eCG treatment group was significantly higher than others, which is similar with glut expression pattern. High glucose level in blood is correlated with increased expression of glucose transporter proteins in rat ovary. Meanwhile, anti-eCG antiserum increased granulosa cell apoptosis in antral follicle compared with those in eCG group. Our observations provide potential explanation for the effects of Glut on follicular development in rat ovary and a role for eCG in the regulation of ovarian glucose uptake. PMID:22870326

  2. STEROIDOGENIC ASSESSMENT USING OVARY CULTURE IN CYCLING RATS: EFFECTS OF BIS(2-DIETHYLHEXYL) PHTHALATE ON OVARIAN STEROID PRODUCTION

    EPA Science Inventory

    In vitro whole-ovary culture in rats was used to characterize ovarian steroidogenesis and to evaluate changes produced by In vivo exposure to bis (2-diethylhexyl) phthalate (DEHP). Steroidogenic profiles [progesterone (P4), estradiol (E2), and testosterone (T)] from minced ovary ...

  3. Neonatal exposure to bisphenol A reduces the pool of primordial follicles in the rat ovary.

    PubMed

    Rodríguez, Horacio A; Santambrosio, Noelia; Santamaría, Clarisa G; Muñoz-de-Toro, Mónica; Luque, Enrique H

    2010-12-01

    We evaluated whether exposure to bisphenol A (BPA) disrupts neonatal follicle development in rats. From postnatal day 1 (PND1) to PND7, pups received corn oil (control), diethylstilbestrol (DES20: 20 μg/kg-d, DES0.2: 0.2 μg/kg-d), or BPA (BPA20: 20mg/kg-d, BPA0.05: 0.05 mg/kg-d). We examined follicular dynamics, multioocyte follicles (MOFs) incidence, proliferation and apoptosis rates, expression of steroid receptors (ERα, ERβ, PR, AR) and cyclin-dependent kinase inhibitor 1B (p27) in PND8 ovaries. DES20, DES0.2 and BPA20-ovaries showed fewer primordial follicles and increased growing follicles. DES20-ovaries exhibited increased incidence of MOFs. Oocyte survival, AR, PR and apoptosis were not changed. Primordial and recruited follicles from BPA20-ovaries showed higher p27, whereas ERβ and proliferation were both increased in recruited follicles. ERα positive primary follicles increased in BPA 20-ovaries. Results show that BPA reduces the primordial follicle pool by stimulating the neonatal initial recruitment, associated with an increased proliferation rate likely mediated by an estrogenic pathway. PMID:20692330

  4. Investigation of the effects of Aloe barbadensis on rat ovaries: a preliminary study.

    PubMed

    Kosif, Rengin; Aktas, R Gülhan

    2009-12-01

    Effects of Aloe barbadensis, a type of Aloe vera, on ovaries were investigated during pregnancy. A. vera gel, a commercial and nontherapeutic form of A. barbadensis, was used for this purpose. Three groups (one control and two test groups) of female Wistar albino rats with no prior births were studied. Group I was administered 25 mg (140 mg/kg) of A. barbadensis/day both orally and through gavage. A. barbadensis was contained in capsules with 500 mg of soybean oil; therefore Group II was administered 500 mg of soybean oil. Group III was the control group. All three groups were given normal food and water ad libitum. The substance had been administered for 20 days until birth. Ovaries were examined histologically. Vascular increase and the hyperemic form of ovary in the group administered A. barbadensis were notable. Decrease in primary follicle numbers, increase in secondary follicle numbers, and diminishment of secondary follicle diameters occurred in ovaries. The histological changes imply an angiogenesis effect of A. barbadensis and an effect like that of follicle-stimulating hormone in ovaries. PMID:20041799

  5. A new rat model exhibiting both ovarian and metabolic characteristics of polycystic ovary syndrome.

    PubMed

    Mannerås, Louise; Cajander, Stefan; Holmäng, Agneta; Seleskovic, Zamira; Lystig, Theodore; Lönn, Malin; Stener-Victorin, Elisabet

    2007-08-01

    Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, abdominal obesity, and insulin resistance. However, its etiology is unclear, and its management is often unsatisfactory or requires a diversified approach. Here, we describe a new rat PCOS model, the first to exhibit both ovarian and metabolic characteristics of the syndrome. Female rats received the nonaromatizable androgen dihydrotestosterone (DHT) or the aromatase inhibitor letrozole by continuous administration, beginning before puberty, to activate androgen receptors. Adult DHT rats had irregular cycles, polycystic ovaries characterized by cysts formed from atretic follicles, and a diminished granulosa layer. They also displayed metabolic features, including increased body weight, increased body fat, and enlarged mesenteric adipocytes, as well as elevated leptin levels and insulin resistance. All letrozole rats were anovulatory and developed polycystic ovaries with structural changes strikingly similar to those in human PCOS. Our findings suggest that the formation of a "hyperplastic" theca interna reflects the inclusion of luteinized granulosa cells in the cyst wall rather than true hyperplasia. We conclude that the letrozole model is suitable for studies of the ovarian features of human PCOS, while the DHT model is suitable for studies of both ovarian and metabolic features of the syndrome. PMID:17495003

  6. The endogenous inhibitor of protein kinase-C in the rat ovary is a protein phosphatase.

    PubMed

    Eyster, K M; Waller, M S; Miller, T L; Miller, C J; Johnson, M J; Persing, J S

    1993-09-01

    Calcium- and lipid-dependent protein kinase (PKC) activity in the ovary of the pseudopregnant rat is masked by an endogenous inhibitor of PKC. These studies were undertaken to examine the mechanism of action of the endogenous inhibitor of PKC in the rat ovary. The addition of the phosphatase inhibitors calyculin-A (0.09 nM), microcystin-LR (6.4 nM), and okadaic acid (10 nM) resulted in the loss of PKC inhibitory activity and an increase in basal PKC activity in rat ovarian cytosol. In phosphatase assays, significant dephosphorylation of histone-III-S or myelin basic protein that had been phosphorylated by PKC occurred within 4 min after the addition of ovarian cytosol from the pseudopregnant rat. This dephosphorylation was prevented from the pseudopregnant rat. This dephosphorylation was prevented by the addition of calyculin-A (0.73 nM) and was removed by fractionation of ovarian cytosol on diethylaminoethyl cellulose. No inhibition of PKC activity was observed when the PKC-specific peptides AcMBP-(4-14) and [Ser25]PKC-(19-31) were used as the substrate for phosphorylation. In addition, rat ovarian cytosol did not exhibit phosphatase activity when the peptide AcMBP-(4-14) was used as the substrate. Addition of ovarian cytosol resulted in dephosphorylation of phosphorylase-alpha phosphorylated by phosphorylase kinase, but not dephosphorylation of histone-II-A or histone-VIII-S phosphorylated by PKA. The data suggest that the endogenous inhibitor of PKC in the rat ovary is a protein phosphatase. PMID:7689949

  7. Inhibition of serotonin reuptake in the prepubertal rat ovary by fluoxetine and effects on ovarian functions.

    PubMed

    Romero-Reyes, Jessica; Cárdenas, Mario; Damián-Matsumura, Pablo; Domínguez, Roberto; Ayala, María Elena

    2016-01-01

    Fluoxetine (FLX), a selective serotonin reuptake inhibitor is an antidepressant in the treatment of mood disorders. Its impact on reproductive processes is incompletely known. The present study analyzed the reproductive effects of FLX in prepubertal female rats. Two experiments were conducted. First (acute administration), 30-day-old female rats were injected intraperitoneally with 5mg/kg of fluoxetine-hydrochloride, and were terminated 24, 48 or 72h after the treatment. Second (subchronic administration), FLX was injected on days 30-33 of age, and the animals were terminated the day of first estrus. In acute treatment estradiol concentration increased to 72h. In subchronic treatment increased serotonin concentration in ovaries and decreased the number of ova shed. An increase in number of atretic follicles and oocyte fragmentation was observed in these animals. The results suggest that FLX acts on the ovary or hypothalamus-pituitary axis resulting in modifications of the follicular development and ovulation. PMID:26746107

  8. [Mechanism of the development of permanent estrus in rats after transplantation of the ovaries into a low temperature medium].

    PubMed

    Vunder, P A; Smetanina, M D

    1983-03-01

    Autotransplantation of the ovaries to the ears of adult rats induces permanent estrus following 5-7 days. Autotransplantation of the ovaries beneath the renal capsules makes the sexual cycle return to normal after the same period. Autotransplantation of the ovaries to the ears of infantile rats brings about pubertas precox followed by normal sexual cycle. Permanent estrus ensues only after 4 months. Transplantation of the ovaries from infantile rats to adult ones and vice versa has shown that age-related differences in the alterations seen in the sexual cycle in response to gonadal transplantation to the ears are caused by age-related differences in the recipients, precisely by those in the cyclic center. PMID:6681996

  9. Locus coeruleus mediates cold stress-induced polycystic ovary in rats.

    PubMed

    Bernuci, Marcelo P; Szawka, Raphael E; Helena, Cleyde V V; Leite, Cristiane M; Lara, Hernán E; Anselmo-Franci, Janete A

    2008-06-01

    Previous reports about the rat ovary have shown that cold stress promotes ovarian morphological alterations related to a polycystic ovary (PCO) condition through activation of the ovarian sympathetic nerves. Because the noradrenergic nucleus locus coeruleus (LC) is activated by cold stress and synaptically connected to the preganglionic cell bodies of the ovarian sympathetic pathway, this study aimed to evaluate the LC's role in cold stress-induced PCO in rats. Ovarian morphology and endocrine and sympathetic functions were evaluated after 8 wk of chronic intermittent cold stress (4 C, 3 h/d) in rats with or without LC lesion. The effect of acute and chronic cold stress upon the LC neuron activity was confirmed by Fos protein expression in tyrosine hydroxylase-immunoreactive neurons. Cold stress induced the formation of follicular cysts, type III follicles, and follicles with hyperthecosis alongside increased plasma estradiol and testosterone levels, irregular estrous cyclicity, and reduced ovulation. Considering estradiol release in vitro, cold stress potentiated the ovarian response to human chorionic gonadotropin. Ovarian norepinephrine (NE) was not altered after 8 wk of stress. However, LC lesion reduced NE activity in the ovary of cold-stressed rats, but not in controls, and prevented all the cold stress effects evaluated. Cold stress increased the number of Fos/tyrosine hydroxylase-immunoreactive neurons in the LC, but this effect was more pronounced for acute stress as compared with chronic stress. These results show that cold stress promotes PCO in rats, which apparently depends on ovarian NE activity that, under this condition, is regulated by the noradrenergic nucleus LC. PMID:18308852

  10. Recovery of ovary function impaired by chemotherapy using Chinese herbal medicine in a rat model.

    PubMed

    Xia, Tian; Fu, Yu; Gao, Hui; Zhao, Zhimei; Zhao, Liying; Han, Bing

    2014-10-01

    The ovary is not only involved in female germ cell development and maturation, but also adjusts female endocrinology. Its function is severely impaired during chemotherapy, and premature ovarian failure may be induced. Chinese herbal medicine (CHM) has displayed significant potential in the treatment of female endocrine disorders; however, it is unknown whether it can recover ovarian function impaired by chemotherapy. In the present study, CHM was used to treat rat models of ovarian dysfunction impaired by chemotherapeutic drugs. Three groups were included in this study: a prevention group, a treatment group, and a prevention-treatment group. Routine gonadotropin-releasing hormone agonists (GnRHa) treatment was used as a control. The results showed that body weight, fertility, estrus days, hormone levels, and ovary weight were restored when CHM was administered in these rat models. Moreover, in the prevention-treatment group, the number of follicles at each developmental stage significantly increased compared with the prevention or treatment group. Furthermore, the number of apoptotic cells significantly decreased, and the relative mRNA expression of caspase-3 significantly decreased, in the prevention-treatment group. The results of gene expression analysis indicated that the expression of anti-Müllerianhormone (AMH) which indicates ovarian preservation was significantly up-regulated in the prevention-treatment group and was similar to normal rats. The expression of growth differentiation factor 9 (GDF9) was significantly enhanced in both the prevention-treatment group and the GnRHa group, which suggested that the oocytes were of better quality. Finally, we found that there were no differences in body weight and fertility in the offspring conceived by the drug-treated rats, which partly indicated the safety of the medicine. In conclusion, Chinese herbal medicine showed a beneficial role in the recovery of ovary function in these rat models and has significant

  11. Dual protective role for Glutathione S-transferase class pi against VCD-induced ovotoxicity in the rat ovary

    SciTech Connect

    Keating, Aileen F.; Sen, Nivedita; Sipes, I. Glenn; Hoyer, Patricia B.

    2010-09-01

    The occupational chemical 4-vinylcyclohexene diepoxide (VCD) selectively destroys ovarian small pre-antral follicles in rats and mice via apoptosis. Detoxification of VCD can occur through glutathione conjugation, catalyzed by glutathione S-transferase (GST) enzymes. Further, GST class pi (GSTp) can negatively regulate JNK activity through protein:protein interactions in extra-ovarian tissues. Dissociation of this protein complex in the face of chemical exposure releases the inhibition of pro-apoptotic JNK. Increased JNK activity during VCD-induced ovotoxicity has been shown in isolated ovarian small pre-antral follicles following in vivo dosing of rats (80 mg/kg/day; 15 days, i.p.). The present study investigated the pattern of ovarian GSTp expression during VCD exposure. Additionally, the effect of VCD on an ovarian GSTp:JNK protein complex was investigated. PND4 F344 rat ovaries were incubated in control medium {+-} VCD (30 {mu}M) for 2-8 days. VCD increased ovarian GSTp mRNA (P < 0.05) relative to control on d4-d8; whereas GSTp protein was increased (P < 0.05) on d6-d8. A GSTp:JNK protein complex was detected by immunoprecipitation and Western blotting in ovarian tissues. Relative to control, the amount of GSTp-bound JNK was increased (P = 0.09), while unbound JNK was decreased (P < 0.05) on d6 of VCD exposure. The VCD-induced decrease in unbound JNK was preceded by a decrease in phosphorylated c-Jun which occurred on d4. These findings are in support of a possible dual protective role for GSTp in the rat ovary, consisting of metabolism of VCD and inhibition of JNK-initiated apoptosis.

  12. Dual protective role for glutathione S-transferase class pi against VCD-induced ovotoxicity in the rat ovary.

    PubMed

    Keating, Aileen F; Sen, Nivedita; Sipes, I Glenn; Hoyer, Patricia B

    2010-09-01

    The occupational chemical 4-vinylcyclohexene diepoxide (VCD) selectively destroys ovarian small pre-antral follicles in rats and mice via apoptosis. Detoxification of VCD can occur through glutathione conjugation, catalyzed by glutathione S-transferase (GST) enzymes. Further, GST class pi (GSTp) can negatively regulate JNK activity through protein:protein interactions in extra-ovarian tissues. Dissociation of this protein complex in the face of chemical exposure releases the inhibition of pro-apoptotic JNK. Increased JNK activity during VCD-induced ovotoxicity has been shown in isolated ovarian small pre-antral follicles following in vivo dosing of rats (80mg/kg/day; 15days, i.p.). The present study investigated the pattern of ovarian GSTp expression during VCD exposure. Additionally, the effect of VCD on an ovarian GSTp:JNK protein complex was investigated. PND4 F344 rat ovaries were incubated in control medium+/-VCD (30muM) for 2-8days. VCD increased ovarian GSTp mRNA (P <0.05) relative to control on d4-d8; whereas GSTp protein was increased (P<0.05) on d6-d8. A GSTp:JNK protein complex was detected by immunoprecipitation and Western blotting in ovarian tissues. Relative to control, the amount of GSTp-bound JNK was increased (P=0.09), while unbound JNK was decreased (P<0.05) on d6 of VCD exposure. The VCD-induced decrease in unbound JNK was preceded by a decrease in phosphorylated c-Jun which occurred on d4. These findings are in support of a possible dual protective role for GSTp in the rat ovary, consisting of metabolism of VCD and inhibition of JNK-initiated apoptosis. PMID:20542051

  13. Studies on gonadotropin receptor of rat ovary and testis

    SciTech Connect

    Zhang, Q.

    1989-01-01

    The subunit structure of the testicular LH/hCG receptor was studied by a chemical cross-linking technique. Leydig cells isolated from rat testis were incubated with {sup 125}I-hCG, following which the bound {sup 125}I-hCG was covalently cross-linked to the receptor on the cell surface with a cleavable or a non-cleavable cross-linking reagent. The hormone-receptor complex was extracted and then either subjected to gel permeation chromatography under nondenaturing conditions, or resolved by SDS-polyacrylamide gel electrophoresis, followed by autoradiographic analysis. The ovarian LH/hCG receptor was studied with luteal cells from pseudopregnant rats. Purification of the receptor was achieved by ligand affinity chromatography following detergent solubilization of the plasma membrane. The purified hCG receptor displayed properties identical to the membrane bound receptor with regard to binding specificity and affinity, and exhibited a molecular weight of approximately 130,000 dalton.

  14. The Characterization of Obese Polycystic Ovary Syndrome Rat Model Suitable for Exercise Intervention

    PubMed Central

    Qiu, Shuwei; Jiang, Zhongli

    2014-01-01

    Objective To develop a new polycystic ovary syndrome (PCOS) rat model suitable for exercise intervention. Method Thirty six rats were randomly divided into three experimental groups: PCOS rats with high-fat diet (PF, n = 24), PCOS rats with ordinary diet (PO, n = 6), and control rats with ordinary diet (CO, n = 6). Two kinds of PCOS rat model were made by adjustment diet structure and testosterone injection for 28 days. After a successful animal model, PF model rats were randomly assigned to three groups: exercise with a continuation of high-fat diet (PF-EF, n = 6), sedentary with a continuation of high-fat diet (PF-SF, n = 6), exercise with an ordinary diet (PF-EO, n = 6). Fasting blood glucose (FBG) and insulin (FINS), estrogen (E2), progesterone (P), and testosterone (T) in serum were determined by RIA, and ovarian morphology was evaluated by Image-Pro plus 6.0. Results Body weight, Lee index, FINS increased significantly in PF rat model. Serum levels of E2 and T were significantly higher in PF and PO than in CO. Ovary organ index and ovarian areas were significant lower in PF than in CO. After intervention for 2 weeks, the levels of 1 h postprandial blood glucose (PBG1), 2 h postprandial blood glucose (PBG2), FINS and the serum levels of T decreased significantly in PF-EF rats and PF-EO rats. The ratio of FBG/FINS was significant higher in PF-EO rats than in PF-SF rats. Ovarian morphology showed that the numbers of preantral follicles and atretic follicles decreased significantly, and the numbers of antral follicles and corpora lutea increased significantly in the rats of PF-EF and PF-EO. Conclusion By combination of high-fat diet and testosterone injection, the obese PCOS rat model is conformable with the lifestyle habits of fatty foods and insufficient exercise, and has metabolic and reproductive characteristics of human PCOS. This model can be applied to study exercise intervention. PMID:24905232

  15. Changes in cyclic GMP level and phosphodiesterase activity during follicular development in the rat ovary.

    PubMed

    Fu, C Q; Shi, F X; Zhang, Z H; Li, J R; Huang, X H; Wang, Z C

    2014-01-01

    Guanosine 3',5'-cyclic monophosphate (cGMP), as a second messenger, plays potential roles in ovarian functions. To elucidate the role of phosphodiesterase (PDE) in cGMP signaling during ovarian follicular development, the present study was conducted to investigate ovarian cGMP level and cGMP-PDE activity by radioimmunoassay (RIA) in postnatal rats, immature rats during gonadotropin-primed follicular development, ovulation and luteinization, adult rats during normal estrous cycle, and aged rats that spontaneously developed persistent estrus (PE). All four rat models were confirmed by histological examination of one ovary, and the other ovary was used for RIA. In postnatal rats, cGMP level was high at birth and decreased dramatically by Day 5, and then, it increased maximally at Day 10 and declined at Day 21. However, cGMP-PDE activity did not significantly change during Days 1 to 10, but increased significantly on Day 21. In immature female rats, cGMP level markedly decreased upon treatment with equine chorionic gonadotropin (eCG), while cGMP-PDE activity did not show any significant changes; however, ovarian cGMP level and cGMP-PDE activity increased after injection of an ovulatory dose of human chorionic gonadotropin (hCG) for induction of ovulation and luteinization. In adult rats during normal estrous cycle, cGMP level was high on proestrus and metestrus days, while cGMP-PDE activity was high on estrus day. In PE rats, ovarian cGMP level was similar to that in adult rats on estrus and diestrus days but lower than that on proestrus and metestrus days; ovarian cGMP-PDE activity was lower than that on estrus days but similar as the other estrous cycle days. In addition, there was a significant negative correlation between ovarian cGMP level and cGMP-PDE activity during normal estrous cycles in the adult rat (r = -0.7715, N = 16, P < 0.05), but not in the postnatal rat (r = -0.1055, N = 20, P > 0.05). Together, the results of our present study indicated that ovarian

  16. Steroidogenesis-related gene expression in the rat ovary exposed to melatonin supplementation

    PubMed Central

    Lima, Gisele Negro; Maganhin, Carla Cristina; Simões, Ricardo Santos; Baracat, Maria Cândida Pinheiro; da Silva Sasso, Gisela Rodrigues; Fuchs, Luiz Fernando Portugal; de Jesus Simões, Manuel; Baracat, Edmund Chada; Júnior, José Maria Soares

    2015-01-01

    OBJECTIVE: To analyze steroidogenesis-related gene expression in the rat ovary exposed to melatonin supplementation. METHODS: Thirty-two virgin adult female rats were randomized to two groups as follows: the control group GI received vehicle and the experimental group GII received melatonin supplementation (10 µg/night per animal) for 60 consecutive days. After the treatment, animals were anesthetized and the collected ovaries were immediately placed in liquid nitrogen for complementary deoxyribonucleic acid microarray analyses. A GeneChip® Kit Rat Genome 230 2.0 Affymetrix Array was used for gene analysis and the experiment was repeated three times for each group. The results were normalized with the GeneChip® Operating Software program and confirmed through analysis with the secondary deoxyribonucleic acid-Chip Analyzer (dChip) software. The data were confirmed by real-time reverse transcription polymerase chain reaction analysis. Genes related to ovarian function were further confirmed by immunohistochemistry. RESULTS: We found the upregulation of the type 9 adenylate cyclase and inhibin beta B genes and the downregulation of the cyclic adenosine monophosphate response element modulator and cytochrome P450 family 17a1 genes in the ovarian tissue of GII compared to those of the control group. CONCLUSION: Our data suggest that melatonin supplementation decreases gene expression of cyclic adenosine monophosphate, which changes ovarian steroidogenesis. PMID:25789524

  17. Effect of prenatal and neonatal exposure to lead on gonadotropin receptors and steroidogenesis in rat ovaries

    SciTech Connect

    Wiebe, J.P.; Barr, K.J.; Buckingham, K.D.

    1988-01-01

    Sprague-Dawley rats were treated with lead chloride (20 or 200 ppm) or sodium chloride (controls) in their drinking water, either prior to pregnancy or during pregnancy and lactation, and female offspring were examined at weaning (21 d) or at 150 d. Other female rats were treated from d 21 to 35. Tissue (blood, kidney, bone) lead levels, body, ovary, and uterus weights, ovarian steroidogenesis, and gonadotropin (luteinizing hormone and follicle-stimulating hormone) levels, and gonadotropin-receptor binding were determined. Prenatal and/or postnatal exposure to lead at these levels (20 and 200 ppm) did not affect tissue weights but did cause a significant decrease in gonadotropin-receptor binding in the prepubertal, pubertal and adult females. Conversion of progesterone to androstenedione and dihydrotestosterone was significantly decreased in 21-d-old rats; in 150-d-old females, the prenatal and/or postnatal exposure to lead resulted in significantly increased conversion to the 5-alpha-reduced steroid, normally high during puberty. The results demonstrate that lead exposure prior to mating may affect gonadotropin-receptor binding in the offspring and that lead exposure (in utero, via mother's milk, or post weaning) may significantly alter steroid production and gonadotropin binding in ovaries of the prepubertal, pubertal, and adult female.

  18. The Effect of Mirtazapine on Cisplatin-Induced Oxidative Damage and Infertility in Rat Ovaries

    PubMed Central

    Altuner, Durdu; Gulaboglu, Mine; Yapca, Omer Erkan; Cetin, Nihal

    2013-01-01

    Cisplatin causes infertility due to ovarian toxicity. The toxicity mechanism is unknown, but evidence suggests oxidative stress. In this study, the effect of mirtazapine on cisplatin-induced infertility and oxidative stress in rats was investigated. 64 female rats were divided into 4 groups of 16. Except for the controls that received physiologic saline only, all were administered with cisplatin (5 mg/kg i.p.) and mirtazapine (15 mg/kg p.o.) or mirtazapine (30 mg/kg p.o.) for 10 days. After this period, six rats from each group were randomly selected, and malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NO), total gluthatione (tGSH), gluthatione peroxidase (GPx), superoxide dismutase (SOD), and 8-hydroxy-2 deoxyguanine (8-OH Gua) levels were measured in their ovarian tissues. Reproductive functions of the remaining rats were examined for 6 months. The MDA, MPO, NO groups and 8-OH Gua levels were higher in the cisplatin-treated groups than the controls, which was not observed in the mirtazapine and cisplatin groups. GSH, GPx, and SOD levels were reduced by cisplatin, which was prevented by mirtazapine. Cisplatin caused infertility by 70%. The infertility rates were, respectively, 40% and 10% for the 15 and 30 mg/kg mirtazapine administered groups. In conclusion, oxidative stress induced by cisplatin in the rat ovary tissue causes infertility in the female rats. Mirtazapine reverses this in a dose-dependent manner. PMID:23737712

  19. Protective effects of honokiol on ischemia/reperfusion injury of rat ovary: an experimental study

    PubMed Central

    Yaman Tunc, Senem; Agacayak, Elif; Goruk, Neval Yaman; Icen, Mehmet Sait; Turgut, Abdulkadir; Alabalik, Ulas; Togrul, Cihan; Ekinci, Cenap; Ekinci, Aysun; Gul, Talip

    2016-01-01

    Aim The purpose of this study was to investigate the protective effect of honokiol on experimental ischemia/reperfusion injury of rat ovary. Materials and methods A total of 40 female Wistar albino rats were used in this study. The rats were divided into five groups as follows: sham (Group I), torsion (Group II), torsion + detorsion (Group III), torsion + detorsion + saline (Group IV), and torsion + detorsion + honokiol (Group V). Bilateral adnexa in all the rats except for those in the sham group were exposed to torsion for 3 hours. The rats in Group IV were administered saline, whereas the rats in Group V were administered honokiol by intraperitoneal route 30 minutes before detorsion. Tissue and plasma concentrations of malondialdehyde and nitric oxide were determined. Ovarian tissue was histologically evaluated. Data analyses were performed by means of Kruskal–Wallis test and Mann–Whitney U-test (Bonferroni correction) in SPSS 15.0 (Statistical Package for Social Sciences; SPSS Inc., Chicago, IL, USA). Results The torsion and detorsion groups had higher scores in vascular congestion, hemorrhage, and inflammatory cell infiltration compared with the sham group (P<0.005). In addition, total histopathological scores were significantly higher in the torsion and detorsion groups compared with the sham group (P<0.005). A significant reduction was observed in hemorrhage, inflammatory cell infiltration, and cellular degeneration scores, of all histopathological scores, in the honokiol group (P<0.005). Ovarian tissue concentrations of malondialdehyde were significantly higher in the torsion and detorsion groups compared with the sham and honokiol groups (P<0.005). Ovarian tissue concentrations of nitric oxide, on the other hand, were significantly higher in the torsion group compared with the sham, saline, and honokiol groups (P<0.005). Conclusion Honokiol has a beneficial effect on ovarian torsion-related ischemia/reperfusion injury. PMID:27022246

  20. Tamoxifen prevents apoptosis and follicle loss from cyclophosphamide in cultured rat ovaries.

    PubMed

    Piasecka-Srader, Joanna; Blanco, Fernando F; Delman, Devora H; Dixon, Dan A; Geiser, James L; Ciereszko, Renata E; Petroff, Brian K

    2015-05-01

    Recent studies documented that the selective estrogen receptor modulator tamoxifen prevents follicle loss and promotes fertility following in vivo exposure of rodents to irradiation or ovotoxic cancer drugs, cyclophosphamide and doxorubicin. In an effort to characterize the ovarian-sparing mechanisms of tamoxifen in preantral follicle classes, cultured neonatal rat ovaries (Day 4, Sprague Dawley) were treated for 1-7 days with active metabolites of cyclophosphamide (i.e., 4-hydroxycyclophosphamide; CTX) (0, 1, and 10 μM) and tamoxifen (i.e., 4-hydroxytamoxifen; TAM) (0 and 10 μM) in vitro, and both apoptosis and follicle numbers were measured. CTX caused marked follicular apoptosis and follicular loss. TAM treatment decreased follicular loss and apoptosis from CTX in vitro. TAM alone had no effect on these parameters. IGF-1 and IGF-1 receptor were assessed in ovarian tissue showing no impact of TAM or CTX on these endpoints. Targeted mRNA analysis during follicular rescue by TAM revealed decreased expression of multiple genes related to inflammation, including mediators of lipoxygenase and prostaglandin production and signaling (Alox5, Pla2g1b, Ptgfr), cytokine binding (Il1r1, Il2rg ), apoptosis (Tnfrsf1a), second messenger signaling (Mapk1, Mapk14, Plcg1), as well as tissue remodeling and vasodilation (Bdkrb2, Klk15). The results suggest that TAM protects the ovary from CTX-mediated toxicity through direct ovarian actions that oppose follicular loss. PMID:25833159

  1. Tamoxifen Prevents Apoptosis and Follicle Loss from Cyclophosphamide in Cultured Rat Ovaries1

    PubMed Central

    Piasecka-Srader, Joanna; Blanco, Fernando F.; Delman, Devora H.; Dixon, Dan A.; Geiser, James L.; Ciereszko, Renata E.; Petroff, Brian K.

    2015-01-01

    Recent studies documented that the selective estrogen receptor modulator tamoxifen prevents follicle loss and promotes fertility following in vivo exposure of rodents to irradiation or ovotoxic cancer drugs, cyclophosphamide and doxorubicin. In an effort to characterize the ovarian-sparing mechanisms of tamoxifen in preantral follicle classes, cultured neonatal rat ovaries (Day 4, Sprague Dawley) were treated for 1–7 days with active metabolites of cyclophosphamide (i.e., 4-hydroxycyclophosphamide; CTX) (0, 1, and 10 μM) and tamoxifen (i.e., 4-hydroxytamoxifen; TAM) (0 and 10 μM) in vitro, and both apoptosis and follicle numbers were measured. CTX caused marked follicular apoptosis and follicular loss. TAM treatment decreased follicular loss and apoptosis from CTX in vitro. TAM alone had no effect on these parameters. IGF-1 and IGF-1 receptor were assessed in ovarian tissue showing no impact of TAM or CTX on these endpoints. Targeted mRNA analysis during follicular rescue by TAM revealed decreased expression of multiple genes related to inflammation, including mediators of lipoxygenase and prostaglandin production and signaling (Alox5, Pla2g1b, Ptgfr), cytokine binding (Il1r1, Il2rg ), apoptosis (Tnfrsf1a), second messenger signaling (Mapk1, Mapk14, Plcg1), as well as tissue remodeling and vasodilation (Bdkrb2, Klk15). The results suggest that TAM protects the ovary from CTX-mediated toxicity through direct ovarian actions that oppose follicular loss. PMID:25833159

  2. Morphometry and immunohistochemistry of follicles growth and steroidogenesis in saharian wild sand rat, Psammomys obesus, ovary.

    PubMed

    Boubekri, Amina; Gernigon-Spychalowicz, Thérese; Khammar, Farida; Exbrayat, Jean-Marie

    2009-01-01

    The sand rat (Psammomys obesus) constitutes a model to study seasonal changes and several metabolic disorders. In order to perform breeding laboratory conditions, the reproductive function of this species living in North Occidental Algerian Sahara was studied. The aim of this work was to investigate the follicular growth changes and the steroidogenic associated aspects. The study was performed using morphometrical and immunohistochemical methods. From primordial to preantral states, the follicle diameter increased progressively from 17-20 mum to 192-225 mum. The preovulatory follicles reached about 500 mum in diameter. Immunoreactivity to progesterone, androstenediol and estradiol, varied in the different parts of the ovary and follicular cells. The progesterone antibody appeared clearly labelled in the theca interna of the growing follicle and increased in the granulosa; the androgen antibody was continuously weak and diffuses in all follicles; the estradiol labelling appeared weak and diffuse in preantral follicles then increased in antral follicles in both theca and granulosa or only in granulosa. In antral follicles, estradiol label was clearly localized in granulosa cells and totally devoid in theca cells. In Psammomys ovary, labels of hormone were diffuse or localized, weak or intense in the theca and or in the granulosa according to the follicle size. PMID:20067896

  3. Expression and regulation of scavenger receptor class B type 1 in the rat ovary and uterus during the estrous cycle.

    PubMed

    Wang, Yalei; Meng, Chenling; Wei, Quanwei; Shi, Fangxiong; Mao, Dagan

    2015-04-01

    Scavenger receptor class B type 1 (SR-B1) preferentially mediates the selective uptake of high density lipoprotein-cholesterol ester and the delivery of cholesterol for steroidogenesis. Although multiple analyses have investigated the function of SR-B1 in the liver, adrenal and ovary, its expression in rat ovary and uterus during the estrous cycle is lacking. In the present study, real-time PCR, western blot and immunohistochemistry (IHC) were used to investigate SR-B1 expression in the rat ovary and uterus during the estrous cycle. The results demonstrated that ovarian SR-B1 expression was in a stage-dependent manner, continuously increased from proestrus and kept elevated during metoestrus, while uterine SR-B1 expression decreased from proestrus to diestrus. To determine whether ovarian and uterine SR-B1 expression were affected by sex steroid hormones, immature rats were treated with 17 β-estradiol (E2), progesterone (P4), or their antagonists from postnatal days 24-26. Results showed that the levels of SR-B1 mRNA and protein were significantly up-regulated by E2 in both the ovary and uterus. IHC results showed that SR-B1 was primarily localized in the oocytes, theca internal cells (T-I) of follicles, interstitial cells (IC) as well as corpus luteum (CL), but not granulosa cells (GC) in the ovary during the estrous cycle. Uterine SR-B1 was highly expressed in the endometrial luminal epithelial cells (LEC) and glandular epithelial cells (GEC) as well as in the circular muscle (CM) cells, and weak staining in stromal cells (SC) through estrous cycle. Taken together, SR-B1 expression in the ovary and uterus across the estrous cycle demonstrate that SR-B1 may be involved in uterine function, follicular development as well as luteal function. PMID:25817199

  4. Metformin regulates ovarian angiogenesis and follicular development in a female polycystic ovary syndrome rat model.

    PubMed

    Di Pietro, Mariana; Parborell, Fernanda; Irusta, Griselda; Pascuali, Natalia; Bas, Diana; Bianchi, María Silvia; Tesone, Marta; Abramovich, Dalhia

    2015-04-01

    Polycystic ovary syndrome (PCOS) is a frequent pathology that affects more than 5% of women of reproductive age. Among other heterogeneous symptoms, PCOS is characterized by abnormalities in angiogenesis. Metformin has been introduced in the treatment of PCOS to manage insulin resistance and hyperglycemia. Besides its metabolic effects, metformin has been shown to improve ovulation, pregnancy and live birth rates in PCOS patients. In the present study, we used a dehydroepiandrosterone-induced PCOS rat model to analyze the effect of metformin administration on ovarian angiogenesis. We found that metformin was able to restore the increased levels of vascular endothelial growth factor, angiopoietin (ANGPT)1, and ANGPT1/ANGPT2 ratio and the decreased levels of platelet-derived growth factor B and platelet-derived growth factor D observed in the dehydroepiandrosterone-treated rats. These effects could take place, at least in part, through a decrease in the levels of serum insulin. We also found an improvement in follicular development, with a lower percentage of small follicles and cysts and a higher percentage of antral follicles and corpora lutea after metformin administration. The improvement in ovarian angiogenesis is likely to restore the accumulation of small follicles observed in PCOS rats and to reduce cyst formation, thus improving follicular development and the percentage of corpora lutea. These results open new insights into the study of metformin action not only in glucose metabolism but also in ovarian dysfunction in PCOS women. PMID:25590243

  5. ALTERED STEROIDOGENESIS IN WHOLE-OVARY AND ADRENAL CULTURE IN CYCLING RATS

    EPA Science Inventory

    Cultures of minced, whole-ovary (whole-ovary culture) were used to determine if three selected chemicals altered steroidogenic profiles. irst, phenolaulfonthalein (PST), when used in culture medium, was tested for its influence on in vitro steroidogenesis. ext, aminoglutethimide ...

  6. Multidrug resistance gene expression correlates with progesterone production in dehydroepiandrosterone-induced polycystic and equine chorionic gonadotropin-stimulated ovaries of prepubertal rats.

    PubMed

    Lee, G Y; Croop, J M; Anderson, E

    1998-02-01

    Polycystic ovaries (PCO) can be induced in prepubertal rats by daily injection of dehydroepiandrosterone (DHEA). There are high levels of progesterone, androgens, and estrogens in the cystic fluid of DHEA-treated rat ovaries. The purpose of this study was to investigate whether high levels of steroids in the PCO correlate with the expression of multidrug resistance gene product P-glycoprotein (Pgp). Using C219, a monoclonal antibody that recognizes the 170-kDa ATP-dependent transmembrane pump, we localized Pgp on the plasma membrane of granulosa cells in cystic follicles but not of oocytes or thecal/interstitial cells. In normal prepubertal rats, Pgp was localized in progesterone-producing granulosa cells of the preovulatory follicles and in cells of the corpora lutea after eCG/hCG stimulation, but not in growing follicles, oocytes, or thecal/interstitial cells. Northern analysis of these tissues indicated strong expression of Pgp mRNA in the preovulatory follicles, cystic follicles, and corpora lutea. From these findings it seems that progesterone produced by the granulosa cells may act in an autocrine manner to induce the expression of Pgp. It may be possible that progesterone interacts with the Pgp of these granulosa cells to modulate steroid efflux. PMID:9475386

  7. Delayed healing and induction of secretory leukocyte protease inhibitor in polycystic ovary syndrome rat skin wounds.

    PubMed

    Jeong, Soon-Jeong; Kim, Sung-Shin; Bae, Chun-Sik; Park, Jin-Ju; Choi, Baik-Dong; Wang, Guanlin; Jung, Myung-Ju; Jang, Hyun-Sun; Kim, Byung-Ock; Lim, Do-Seon; Cho, Young-Sik; Jeong, Moon-Jin

    2012-02-01

    Secretory leukocyte protease inhibitor (SLPI) and estrogen promote wound healing through a decrease in the excessive inflammatory response, accelerating re-epithelialization and increasing the amount of collagen deposition. The excessive administration of estradiol valerate (EV) using hormonal therapy decreases the concentration of estrogen abruptly and induces the polycystic ovary syndrome (PCOS). In this study, the PCOS rat skin wound area was wider than that of the normal groups and the rate of keratinocyte migration in PCOS was lower than the normal group. The numbers of inflammatory cells and macrophages recruited in the PCOS group were larger than that of the normal group. More collagen was deposited in the healing area of the normal group than in the PCOS group. The level of SLPI expression was higher in the PCOS group than the normal group after wounding, with the exception of the epithelium. On the other hand, mRNA and protein expression levels of transforming growth factor-β1 (TGF-β1) were lower in the PCOS group than in the normal group. Matrix metalloproteinase-2 (MMP-2) and MMP-9 levels in the PCOS group were significantly lower than that of the normal group. Therefore, increased SLPI in PCOS skin wounds may help prevent an excessive inflammatory response and aberrant collagen deposition but not are sufficient to accelerate PCOS skin wound healing, suggesting that SLPI may act as a local rather than a systemic modulating molecule in PCOS rat skin wounds. PMID:22020578

  8. Increase of kisspeptin-positive cells in the hypothalamus of a rat model of polycystic ovary syndrome.

    PubMed

    Kondo, Mika; Osuka, Satoko; Iwase, Akira; Nakahara, Tatsuo; Saito, Ai; Bayasula; Nakamura, Tomoko; Goto, Maki; Kotani, Tomomi; Kikkawa, Fumitaka

    2016-06-01

    Kisspeptin, a hypothalamic neuropeptide, is expressed in the arcuate nucleus (ARC) that is considered as the center of the gonadotropin-releasing hormone (GnRH)-pulse generator. We hypothesized that kisspeptin expressed in the ARC is implicated in the disturbance of the hypothalamus-pituitary-ovary axis observed in polycystic ovary syndrome (PCOS). To test this hypothesis, we evaluated the hormonal profiles, luteinizing hormone (LH) pulse, and ARC kisspeptin immunoreactivity in a PCOS rat model using the anti-progestin RU486. We found an alteration of the LH pulse, including a trend towards an increased mean LH concentration and area under the curve, and a significant upregulation of the mean LH pulse amplitude. Additionally, a higher number of kisspeptin-positive cells was observed in the ARC of RU486-treated rats than in the ARC of intact rats. These results suggest the possible involvement of hypothalamic kisspeptin in the hypothalamus-pituitary-ovary axis and therefore, in PCOS pathophysiology. PMID:26864582

  9. Modulation of Cx43 and Gap Junctional Intercellular Communication by Androstenedione in Rat Polycystic Ovary and Granulosa Cells in vitro

    PubMed Central

    Talhouk, Rabih; Tarraf, Charbel; Kobrossy, Laila; Shaito, Abdallah; Bazzi, Samer; Bazzoun, Dana; El-Sabban, Marwan

    2012-01-01

    Background Gap-junctional intercellular communication (GJIC) is implicated in physicological processes and it is vitally important for granulosa cell (GC) differentiation and oocyte growth. We investigated the expression of connexin 43 (Cx43), a gap junctional protein, in normal and androstenedione-induced polycystic ovary (PCO), the effects of androstenedione on Cx43 expression, GJIC and progesterone production in granulosa cells in vitro. Methods Isolated GCs from rat ovary were supplemented with FSH and dripped with EHS-matrix (EHS-drip) in culture media, were treated with physiological (10−7 M) or pathological (10−5 M) androstenedione concentrations to induce differentiation. Cx43 protein levels were assessed by Western blotting. Immunohistochemistry was also used to determine the localization of Cx43 in GCs and corpus luteum (CL) of controls and PCOs. Differentiation of GCs was determined by progesterone assay and Lucifer yellow dye transfer for GJIC status. The degree of significance of variations between the results was analyzed by ANOVA using SPSS (version 11.5; 2002). Results Cx43 localized in the GC layer of both the control and PCOs. Its protein levels were upregulated in PCO rat ovaries. GCs in culture with or without androstenedione had a punctate membranous distribution of Cx43. However, androstenedione increased GJIC and upregulated progesterone and Cx43 protein levels. Inhibiting GJIC by 18-α GA in androstenedione-treated GCs caused partial inhibition of progesterone production, suggesting a possible role of GJIC in mediating the action of androstenedione on GC differentiation. Conclusion This study presented a suitable culture model for polycystic ovary syndrome and showed that Cx43 and GJIC might contribute to the pathogenesis of polycystic ovary syndrome. PMID:23926521

  10. Effects of Spirulina on Cyclophosphamide-Induced Ovarian Toxicity in Rats: Biochemical and Histomorphometric Evaluation of the Ovary

    PubMed Central

    Yener, Nese Arzu; Sinanoglu, Orhun; Ilter, Erdin; Celik, Aygen; Sezgin, Gulbuz; Midi, Ahmet; Aksungar, Fehime

    2013-01-01

    Cyclophosphamide (Cyc) is known to cause ovotoxicity and infertility in women. Our aim is to investigate the possible ovotoxic effects of Cyc and possible antioxidant and protective effects of blue-green algae, Spirulina (Sp), in rat ovaries. Eighteen rats were given: group I (n = 6, control); group II (n = 6, CP), a single dose Cyc; group III (n = 6, Sp+Cyc), 7 days Sp+single dose Cyc. Tissue malondialdehyde (MDA) levels, superoxide dismutase (SOD), and catalase (CAT) activities are assessed biochemically. Normal and atretic primordial and primary follicle counts for all sections obtained for each ovary are calculated. Mean number of follicle counts for each group are compared. In Sp+Cyc group, tissue MDA levels were significantly lower than those in the CP and higher than those in the C group (CP > Sp+Cyc > C). Tissue SOD activity was significantly higher in Sp+Cyc group than that in the CP group and lower than that in the C group (C > Sp+Cyc > C). No statistically significant difference was found between the ovarian CAT activities in any group. Histomorphometrically, there was also no significant difference between the mean numbers of normal and atretic small follicle counts. Our results suggest that single dose Cyc has adverse effects on oxidant status of the ovaries and Sp has protective effects in Cyc-induced ovotoxicity. PMID:23762559

  11. Disruption in the expression and immunolocalisation of steroid receptors and steroidogenic enzymes in letrozole-induced polycystic ovaries in rat.

    PubMed

    Zurvarra, Francisco M; Salvetti, Natalia R; Mason, J Ian; Velazquez, Melisa M L; Alfaro, Natalia S; Ortega, Hugo H

    2009-01-01

    The objective of the present study was to characterise the expression and tissue distribution of steroid receptors (oestrogen receptor-alpha and -beta (ERalpha, ERbeta), androgen receptor (AR) and progesterone receptor (PR)) and steroidogenic enzymes (P450 aromatase (P450arom), 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and steroidogenic acute regulatory protein (StAR)) in letrozole-induced polycystic ovaries of rats. Changes in serum hormone levels, protein expression in whole ovaries by western blot analysis and protein localisation by immunohistochemistry were determined in female rats treated with the aromatase inhibitor letrozole and compared with controls in proestrous and diestrous rats. Increases in the serum LH, FSH and testosterone concentrations were observed in letrozole-treated rats whereas serum oestradiol and progesterone levels were reduced. Protein expression as analysed by western immunoblot was consistent with the immunohistochemical data. Letrozole treatment induced an increase in the expression of AR, StAR and 3beta-HSD and a decrease in ERbeta. ERalpha, PR and P450arom showed partial changes in relation to some cycle stages. These results indicate that cystogenesis in this experimental model is characterised by changes in steroid receptors and steroidogenic enzyme expression that may be essential to proper ovarian functioning and are in agreement with similar changes observed in women with PCOS. PMID:19698287

  12. Transcutaneous electrical acupoint stimulation alleviates the hyperandrogenism of polycystic ovarian syndrome rats by regulating the expression of P450arom and CTGF in the ovaries

    PubMed Central

    Qu, Fan; Liang, Yi; Zhou, Jue; Ma, Rui-Jie; Zhou, Jie; Wang, Fang-Fang; Wu, Yan; Fang, Jian-Qiao

    2015-01-01

    The present study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) in alleviating the hyperandrogenism of polycystic ovarian syndrome (PCOS) model rats induced by testosterone propionate and the possible underlying mechanism. Thirty-six female Sprague-Dawley rats were randomly divided into normal control, PCOS model and TEAS groups with twelve rats in each group. The PCOS model rats were established by single injection of testosterone propionate at 9th day after birth, and the status of estrous cyclicity for each rat was observed. When the 8-week TEAS treatment completed, the weight of body, uterus and ovaries of the rats were respectively measured. The serum levels of total testosterone (TT), sex hormone binding globulin (SHBG), androstenedione, luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E2) were detected. The mRNA and protein expression levels of aromatase cytochrome P450 (P450arom) and connective tissue growth factor (CTGF) in the ovaries of the rats were respectively measured with real-time quantitative PCR and immunohistochemistry. The TEAS treatment significantly improved the estrous cycles of the PCOS rats and the TEAS group displayed significantly lower average body and ovaries weights than the PCOS model group (P < 0.05). TEAS significantly decreased the serum TT, free androgen index (FAI), androstenedione and LH/FSH levels, and increased the serum FSH levels of the PCOS rats (P < 0.05). The TEAS treatment significantly increased the P450arom mRNA as well as protein expression levels and significantly decreased the CTGF mRNA as well as protein expression levels in the ovaries of the PCOS rats (P < 0.05). We concluded that it is through regulating the P450arom and CTGF expression levels in the ovaries that TEAS significantly alleviates the hyperandrogenism of PCOS rats induced by testosterone propionate. PMID:26221326

  13. Transitory activation of the central and ovarian norepinephrine systems during cold stress-induced polycystic ovary in rats.

    PubMed

    Bernuci, M P; Leite, C M; Barros, P; Kalil, B; Leoni, G B; Del Bianco-Borges, B; Franci, C R; Szawka, R E; Lara, H E; Anselmo-Franci, J A

    2013-01-01

    Cold stress-induced ovarian sympathetic activation is associated with the development of ovarian cysts in rats. Although we have hypothesised that polycystic ovary (PCO) features induced by cold stress, as prevented by lesion of the noradrenergic nucleus locus coeruleus (LC), were a result of the increased activity of the ovarian norepinephrine (NE) system, this was not evident after 8 weeks of stress. In the present study, we investigated the temporal changes in LC and ovarian NE activities and steroid secretion in rats exposed to single (SS) or repeated (RS) cold stress. SS and 4 week (4W)-RS but not 8 week (8W)-RS increased c-Fos expression in the LC and ovarian NE release. Plasma oestradiol, testosterone and progesterone levels tended to increase in 4W-RS and were elevated in 8W-RS rats, which displayed PCO morphology. β-adrenergic receptor agonist increased steroid hormone release from the ovary of unstressed (US) but not from 8W-RS rats. To determine whether increased activity of noradrenergic system during the initial 4 weeks of RS would be sufficient to promote PCO, rats were exposed to 4 weeks of cold stress and kept in ambient temperature for the next 4 weeks (4W-RS/4W-US). Accordingly, PCO morphology, increased steroid secretion and decreased ovulation rate were found in 4W-RS/4W-US rats, strengthening the hypothesis that the initial increase in NE release triggers the development of PCO. The correlated activity of LC neurones and ovarian noradrenergic terminals and the induction of PCO in 4W-RS/4W-US rats provide functional evidence for a major role of NE in disrupting follicular development and causing the long-lasting endocrine abnormalities found in stress-induced PCO. PMID:22882492

  14. Steroid hormone production in testis, ovary, and adrenal gland of immature rats irradiated in utero with /sup 60/Co

    SciTech Connect

    Inano, H.; Suzuki, K.; Ishii-Ohba, H.; Imada, Y.; Kumagai, R.; Kurihara, S.; Sato, A.

    1989-02-01

    Pregnant rats received whole-body irradiation at 20 days of gestation with 2.6 Gy lambda rays from a 60Co source. Endocrinological effects before maturation were studied using testes and adrenal glands obtained from male offspring and ovaries from female offspring irradiated in utero. Seminiferous tubules of the irradiated male offspring were remarkably atrophied with free germinal epithelium and containing only Sertoli cells. Female offspring also had atrophied ovaries. Testicular tissue obtained from intact and 60Co-irradiated rats was incubated with 14C-labeled pregnenolone, progesterone, 17 alpha-hydroxyprogesterone, and androstenedione as a substrate. Intermediates for androgen production and catabolic metabolites were isolated after the incubation. The amounts of these metabolites produced by the irradiated testes were low in comparison with the control. The activities of delta 5-3 beta-hydroxysteroid dehydrogenase, 17 alpha-hydroxylase, C17,20-lyase, and delta 4-5 alpha-reductase in the irradiated testes were 30-40% of those in nonirradiated testes. Also, the activities of 17 beta- and 20 alpha-hydroxysteroid dehydrogenases were 72 and 52% of the control, respectively. In adrenal glands, the 21-hydroxylase activity of the irradiated animals was 38% of the control, but the delta 5-3 beta-hydroxysteroid dehydrogenase activity was comparable to that of the control. On the other hand, the activity of delta 5-3 beta-hydroxysteroid dehydrogenase of the irradiated ovary was only 19% of the control. These results suggest that 60Co irradiation of the fetus in utero markedly affects the production of steroid hormones in testes, ovaries, and adrenal glands after birth.

  15. Analysis of the effects of increasing doses of ionizing radiation to the exteriorized rat ovary on follicular development, atresia, and serum gonadotropin levels

    SciTech Connect

    Jarrell, J.; YoungLai, E.V.; Barr, R.; O'Connell, G.; Belbeck, L.; McMahon, A.

    1986-02-01

    There is increasing interest in the effects of environmental and therapeutic agents on the reproductive system, in particular, the ovary. To study the effects of controlled doses of ionizing radiation to the ovary, Sprague-Dawley rats had their ovaries exteriorized and subjected to increasing doses of radiation. There was a significant increase in ovarian follicular atresia, a significant increase in serum follicle-stimulating hormone levels, but no change in serum luteinizing hormone levels. This experimental protocol may facilitate the testing putative radioprotectants.

  16. Systems pharmacology to investigate the interaction of berberine and other drugs in treating polycystic ovary syndrome.

    PubMed

    Wang, Yu; Fu, Xin; Xu, Jing; Wang, Qiuhong; Kuang, Haixue

    2016-01-01

    Polycystic ovary syndrome (PCOS) is a common multifactorial endocrine disorder among women of childbearing age. PCOS has various and heterogeneous clinical features apart from its indefinite pathogenesis and mechanism. Clinical drugs for PCOS are multifarious because it only treats separate symptoms. Berberine is an isoquinoline plant alkaloid with numerous biological activities, and it was testified to improve some diseases related to PCOS in animal models and in humans. Systems pharmacology was utilized to predict the potential targets of berberine related to PCOS and the potential drug-drug interaction base on the disease network. In conclusion, berberine is a promising polypharmacological drug for treating PCOS, and for enhancing the efficacy of clinical drugs. PMID:27306862

  17. Systems pharmacology to investigate the interaction of berberine and other drugs in treating polycystic ovary syndrome

    PubMed Central

    Wang, Yu; Fu, Xin; Xu, Jing; Wang, Qiuhong; Kuang, Haixue

    2016-01-01

    Polycystic ovary syndrome (PCOS) is a common multifactorial endocrine disorder among women of childbearing age. PCOS has various and heterogeneous clinical features apart from its indefinite pathogenesis and mechanism. Clinical drugs for PCOS are multifarious because it only treats separate symptoms. Berberine is an isoquinoline plant alkaloid with numerous biological activities, and it was testified to improve some diseases related to PCOS in animal models and in humans. Systems pharmacology was utilized to predict the potential targets of berberine related to PCOS and the potential drug-drug interaction base on the disease network. In conclusion, berberine is a promising polypharmacological drug for treating PCOS, and for enhancing the efficacy of clinical drugs. PMID:27306862

  18. Exposure of Female Rats to an Environmentally Relevant Mixture of Brominated Flame Retardants Targets the Ovary, Affecting Folliculogenesis and Steroidogenesis.

    PubMed

    Lefèvre, Pavine L C; Berger, Robert G; Ernest, Sheila R; Gaertner, Dean W; Rawn, Dorothea F K; Wade, Michael G; Robaire, Bernard; Hales, Barbara F

    2016-01-01

    Brominated flame retardants (BFRs) are incorporated into various consumer products to prevent flame propagation. These compounds leach into the domestic environment, resulting in chronic exposure and contamination. Pregnancy failure is associated with high levels of BFRs in human follicular fluid, raising serious questions regarding their impact on female reproductive health. The goal of this study is to elucidate the effects of an environmentally relevant BFR mixture on female rat ovarian functions (i.e., folliculogenesis and steroidogenesis). A BFR dietary mixture formulated to mimic the relative BFR congener levels in North American house dust was administered to adult female Sprague-Dawley rats from 2 to 3 wk before mating until Gestational Day 20; these diets were designed to deliver nominal doses of 0, 0.06, 20, or 60 mg/kg/day of the BFR mixture. Exposure to BFRs triggered an approximately 50% increase in the numbers of preantral and antral follicles and an enlargement of the antral follicles in the ovaries of the dams. A significant reduction in the expression of catalase, an antioxidant enzyme, and downregulation of the expression of insulin-like factor 3 (Insl3) and 17alpha-hydroxylase (Cyp17a1) were observed in the ovary. In addition, BFR exposure affected steroidogenesis; we observed a significant decrease in circulating 17-hydroxypregnenolone and an increase in testosterone concentrations in BFR-exposed dams. Thus, BFRs target ovarian function in the rat, adversely affecting both folliculogenesis and steroidogenesis. PMID:26607716

  19. Homing and restorative effects of bone marrow-derived mesenchymal stem cells on cisplatin injured ovaries in rats.

    PubMed

    Liu, Jiabin; Zhang, Haiying; Zhang, Yun; Li, Nan; Wen, Yuku; Cao, Fanglei; Ai, Hao; Xue, Xiaoou

    2014-12-31

    Premature ovarian failure (POF) is a long-term adverse effect of chemotherapy treatment. However, current available treatment regimens are not optimal. Emerging evidence suggests that bone marrow-derived mesenchymal stem cells (BMSCs) could restore the structure and function of injured tissues, but the homing and restorative effects of BMSCs on chemotherapy injured ovaries are still not clear. In this study, we found that granulosa cell (GC) apoptosis induced by cisplatin was reduced when BMSCs were migrated to granulosa cells (GCs) in vitro. Chemotherapy-induced POF was induced by intraperitoneal injection of cisplatin in rats. BMSCs labeled with enhanced green fluorescent protein (EGFP) were injected into the rats via the tail vein to investigate the homing and distribution of BMSCs in vivo. The number of BMSCs in the ovarian hilum and medulla was greater than in the cortex, but no BMSCs were found in the follicles and corpus lutea. In addition, the BMSCs treatment group's antral follicle count and estradiol levels increased after 30 days, compared with the POF group. Hence, our study demonstrates that intravenously delivered BMSCs can home to the ovaries, and restore its structure and function in POF model rats. PMID:25410907

  20. Ample Evidence: Dehydroepiandrosterone (DHEA) Conversion into Activated Steroid Hormones Occurs in Adrenal and Ovary in Female Rat

    PubMed Central

    Zhou, Yingqiao; Kang, Jian; Chen, Di; Han, Ningning; Ma, Haitian

    2015-01-01

    Dehydroepiandrosterone (DHEA) is important for human health, especially for women. All estrogens and practically half of androgens are synthesized from DHEA in peripheral tissues. However, the mechanism and exact target tissues of DHEA biotransformation in the female are not fully clear. The present study showed that maximal content of androstenedione (AD) and testosterone (T) were observed at 3h after DHEA administration in female rats, which was 264% and 8000% above the control, respectively. Estradiol (E2) content significantly increased at 6h after DHEA administration, which was 113% higher than that in control group. Gavage with DHEA could significantly reduce 3β-hydroxysteroid dehydrogenase (3β-HSD) mRNA level at 3-12h and 17β-hydroxysteroid dehydrogenase (17β-HSD) mRNA level at 12h in ovary, while increasing aromatase mRNA levels at 6, 24, and 48h. It is interesting that administration of DHEA caused a significant increase of 17β-HSD, 3β-HSD and aromatase mRNA levels in adrenal. The AD and T contents also markedly increased by 537% and 2737% after DHEA administration in ovariectomised rats, in company with a significant increase in 17β-HSD and 3β-HSD mRNA levels and decreased aromatase mRNA level in adrenal. However, DHEA administration did not restore the decreased E2, estrone (E1), and progesterone (P) caused by the removal of the ovaries in females. These results clearly illustrated that exogenous DHEA is preferentially converted into androgens in adrenal, while its conversion to estrogens mainly happens in the ovary through steroidogenic enzyme in female rats. PMID:25962158

  1. Stereological study on the effect of vitamin C in preventing the adverse effects of bisphenol A on rat ovary

    PubMed Central

    Soleimani Mehranjani, Malek; Mansoori, Tayebeh

    2016-01-01

    Background: Bisphenol A (BPA), an environmental pollutant, can generate free radicals which damages the reproductive system. Vitamin C is an antioxidant which may prevent the adverse effects of free radicals. Objective: The aim was to investigate the effect of vitamin C on the ovary tissue in rats treated with BPA. Materials and Methods: In this experimental study, 24 female Wistar rats (200±20 gr) were randomly divided into 4 groups (n=6): control, BPA (60 µg/Kg/day), vitamin C (150 mg/Kg/day) and BPA + vitamin C and orally treated for 20 days. The left ovaries were taken out, fixed for tissue processing and studied using stereological methods. Data were analyzed with SPSS using one-way ANOVA, and the means were considered significantly different at (p<0.05). Results: The total volume of ovary and cortex (p<0.01), medulla (p<0.05), the volume of corpus luteum (p<0.001) and the mean number of antral follicles (p<0.001) significantly reduced in BPA group compared with control, while the number of atretic follicles increased (p<0.05). The volume of oocyte (p<0.01) and its nucleus (p<0.001) in the antral follicles and the thickness of zona pellucida (ZP) in the secondary (p<0.05) and antral (p<0.001) follicles significantly decreased in BPA group compared with controls. The above parameters in the BPA + vitamin C group were compensated to control level. Conclusion: Vitamin C can be used as a potential antioxidant in the case of BPA toxication PMID:27525324

  2. FOXO3a is involved in the apoptosis of naked oocytes and oocytes of primordial follicles from neonatal rat ovaries.

    PubMed

    Liu, Hong; Luo, Li-Li; Qian, Yuan-Shu; Fu, Yu-Cai; Sui, Xu-Xia; Geng, Yi-Jie; Huang, Da-Na; Gao, Shi-Tong; Zhang, Ren-Li

    2009-04-17

    Inhibition of the forkhead transcription factor, FOXO3a, can promote the transition from primordial to primary follicle and subsequent follicle development in mammalian ovaries. Stem cell factor (SCF) initiates anti-apoptotic signaling from its membrane receptor, c-kit, to Bcl-2 family members through PI3K/AKT in oocytes of primordial follicles. However, whether FOXO3a mediates the apoptosis of naked oocytes and oocytes of primordial follicles remains unknown. In the present study, oocytes from nests and primordial follicles from neonatal rat ovaries were cultured, and oocyte apoptosis was examined using the TUNEL technique. The pro-apoptotic action of FOXO3a and the potential signal transduction pathways were investigated using RT-PCR, Western blot, and immunocytochemistry. Culturing oocytes in the presence of SCF did not affect the level of total FOXO3a protein, but rapidly elevated the level of phosphorylated FOXO3a (indicating functional suppression). As phosphorylated FOXO3a increased, oocyte apoptosis was inhibited. The specific PI3K/Akt inhibitor, LY 294002, abolished the phosphorylation of FOXO3a and the anti-apoptotic action of SCF. SCF down-regulated the expression of p27KIP1 and pro-apoptotic factors such as Bim, Bad, and Bax, and this activity was reversed by LY 294002. SCF up-regulated the expression of MnSOD, which was also inhibited by LY 294002. However, SCF had no effect on Bcl-2 protein. These results suggest that FOXO3a is involved in oocyte apoptosis in the neonatal rat ovary, and the SCF-PI3K/Akt-FOXO3a signaling pathway mediates oocyte apoptosis and primordial follicle formation. PMID:19258007

  3. Vasoactive intestinal peptide enhanced aromatase activity in the neonatal rat ovary before development of primary follicles or responsiveness to follicle-stimulating hormone

    SciTech Connect

    George, F.W.; Ojeda, S.R.

    1987-08-01

    The authors have investigated the factors that regulate aromatase activity in fetal-neonatal rat ovaries. Ovarian aromatase activity (assessed by measuring the amount of /sup 3/H/sub 2/O formed from (1..beta..-/sup 3/H)testosterone) is low prior to birth and increases to values greater than 30 pmol/hr per mg of protein between days 8 and 12 after birth. The appearance of ovarian aromatase coincides with the development of primordial follicles. Fetal-neonatal ovaries maintained in serum-free organ culture do not develop aromatase activity at the expected time. Ovine follicle-stimulating hormone, ovine luteinizing hormone, or their combination failed to induce the enzyme activity in cultured fetal ovaries, whereas follicle-stimulating hormone is effective in preventing the decline in aromatase activity when postnatal day 8 ovaries are placed in culture. In contrast to follicle-stimulating hormone, dibutyryl-cAMP markedly enhances ovarian aromatase in cultured fetal ovaries. Likewise, enhancement of endogenouse cAMP formation with forskolin or cholera toxin caused an increase in enzyme activity within 24 hr. Vasoactive intestinal peptide, a peptide known to occur in ovarian nerves, caused a dose-dependent increase in aromatase activity in fetal ovaries prior to folliculogenesis. Of related peptides tested, only the peptide having N-terminal histidine and C-terminal isoleucine amide was capable of inducing aromatase activity in fetal ovaries. The fact that VIP can induce aromatase activity in fetal rat ovaries prior to follicle formation and prior to responsiveness to follicle-stimulating hormone suggests that this neuropeptide may play a critical role in ovarian differentiation.

  4. Trace glucose and lipid metabolism in high androgen and high-fat diet induced polycystic ovary syndrome rats

    PubMed Central

    2012-01-01

    Background There is a high prevalence of diabetes mellitus (DM) and dyslipidemia in women with polycystic ovary syndrome (PCOS). The purpose of this study was to investigate the role of different metabolic pathways in the development of diabetes mellitus in high-androgen female mice fed with a high-fat diet. Methods Female Sprague-Dawley rats were divided into 3 groups: the control group(C), n = 10; the andronate-treated group (Andronate), n = 10 (treated with andronate, 1 mg/100 g body weight/day for 8 weeks); and the andronate-treated and high-fat diet group (Andronate+HFD), n = 10. The rate of glucose appearance (Ra of glucose), gluconeogenesis (GNG), and the rate of glycerol appearance (Ra of glycerol) were assessed with a stable isotope tracer. The serum sex hormone levels, insulin levels, glucose concentration, and the lipid profile were also measured. Results Compared with control group, both andronate-treated groups exhibited obesity with higher insulin concentrations (P < 0.05) but similar blood glucose concentrations. Of the two andronate-treated groups, the andronate+HFD group had the most serious insulin resistance (IR). Estrus cycles were completely acyclic, with polycystic ovaries and elevated serum lipid profiles in the andronate+HFD group (P < 0.05). Ra of glucose and GNG increased significantly in the andronate+HFD rats. However, the Ra of glycerol was similar in the three groups. Conclusions Andronate with HFD rat model showed ovarian and metabolic features of PCOS, significant increase in glucose Ra, GNG, and lipid profiles, as well as normal blood glucose levels. Therefore, aberrant IR, increased glucose Ra, GNG, and lipid metabolism may represent the early-stage of glucose and lipid kinetics disorder, thereby might be used as potential early-stage treatment targets for PCOS. PMID:22276997

  5. Role of oxidative stress and low-grade inflammation in letrozole-induced polycystic ovary syndrome in the rat.

    PubMed

    Pandey, Vivek; Singh, Anusha; Singh, Ajit; Krishna, Amitabh; Pandey, Uma; Tripathi, Yamini Bhusan

    2016-03-01

    The aims of the current study were to examine the effects of temporal changes in oxidative stress (OS) and low-grade inflammation in letrozole-treated rats and to correlate these changes with the development of polycystic ovary syndrome (PCOS)-like features. Rats were treated with letrozole for 7, 15 and 21 days to induce PCOS. On day 7 of the treatment, a significant increase in serum testosterone and high sensitive C-reactive protein (hsCRP), the low-grade inflammatory marker, was found in the letrozole treated rats compared to control rats. Moreover, a decreased immunoexpression of insulin receptor coincided with increased body weight. The strong correlation between the levels of hsCRP and lipid peroxidation (LPO) suggests simultaneous development of low-grade inflammation and OS in response to hyperandrogenism, and the role of OS in a formation of cystic follicles in the letrozole animal PCOS model. Therefore, the results of the present study suggest that OS and low-grade inflammation (hsCRP) are the major causes of PCOS induction in this model. PMID:26952756

  6. Effects of hypophysectomy and administration of pituitary hormones on luteal function and uptake of high density lipoproteins by luteinized ovaries and adrenals of the rat

    SciTech Connect

    Murphy, B.D.; Rajkumar, K.; McKibbin, P.E.; Macdonald, G.J.; Buhr, M.M.; Grinwich, D.L.

    1985-04-01

    The role of plasma lipoproteins and hypophyseal hormones in the maintenance of progesterone secretion by the rat corpus luteum was investigated. In the first experiment, rats were treated daily from days 1-6 of pregnancy with 5 mg/kg 4-aminopyrozolopyramidine (4APP), a blocker of hepatic lipoprotein secretion, or with 5 mg/kg 4APP and 1 or 2 mg ovine PRL or 0.1 ml 0.5% phosphoric acid (4APP vehicle). The administration of 4APP reduced serum cholesterol and progesterone levels on days 2-6 of pregnancy and ovarian progesterone on day 6. The reduced progesterone secretion had no effect on embryo implantation. PRL, in the doses used, was incapable of abrogating the effects of 4APP on circulating or ovarian progesterone levels. Ovaries and adrenals, but not kidneys, of pseudopregnant rats exhibited specific and saturable uptake of porcine high density lipoprotein (HDL). Time-course studies indicated that the uptake of HDL was rapid in ovaries compared to that in adrenals. Ovaries from rats not only exhibited uptake of porcine HDL, but also were capable of using it for progesterone synthesis. Treatment with 4APP increased the adrenal uptake of HDL, but ovarian uptake was not different from that in the control group. Hypophysectomy reduced both adrenal and ovarian uptake of HDL. In adrenals only ACTH at the dose employed ameliorated reduction of HDL uptake induced by hypophysectomy, while in the ovaries, both PRL and LH reversed the effect of hypophysectomy. The effect of PRL on uptake was specific to (/sup 125/I)HDL and did not alter (/sup 125/I)albumin uptake. It is concluded that: 1) hypophysectomy reduces HDL uptake in the luteinized rat ovary; and 2) PRL and LH replacement therapy maintain ovarian uptake of HDL, suggesting a direct effect of these luteotropins on lipoprotein uptake.

  7. 20-alpha-Hydroxysteroid dehydrogenase from pseudopregnant rat ovary: obtention and characterization of a monoclonal antibody against the enzyme activity.

    PubMed

    De La Llosa-Hermier, M P; Nocart, M; Paly, J; Hermier, C

    1992-12-01

    The enzyme 20-alpha-hydroxysteroid dehydrogenase (20-alpha-HSD) was purified from pseudopregnant rat ovaries and used as antigen for the development of a monoclonal antibody by the hybridoma technique. Spleen cells of BALB/c mice immunized with purified 20-alpha-HSD were fused with SP2/0 mouse myeloma cells. Among the colonies of hybrid cells, one (designated mAb-HSD 11) was found to be secreting antibodies (IgM) able to inhibit 20-alpha-HSD activity. The antibody-secreting hybridome was amplified by ascitic fluid production and the monoclonal antibody purified by Bakerbond ABx procedure. Purified mAb-HSD 11 was able to inhibit 20-alpha-HSD activity in a dose-dependent manner. Studies of Michaelis constants of 20-alpha-HSD indicate that this monoclonal antibody increases the Km for 20-alpha-dihydroprogesterone and decreases the Vmax. PMID:1292619

  8. Use of Aroclor 1254-induced rat liver homogenate in the assaying of promutagens in Chinese hamster ovary cells

    SciTech Connect

    Li, A.P.

    1984-01-01

    Seven promutagens belonging to two chemical classes - polycyclic aromatic hydrocarbons (PAHs) and alkyl nitrosamines - were studied in Chinese hamster ovary (CHO) cells. Findings of practical importance in the use of Aroclor 1254-induced rat liver homogenate (S9) in the CHO/hypoxanthine-guanine phosphoribosyl transferase (HGPRT) mutation assay were made. Novel findings are (1) the inclusion of CaCl/sub 2/ in the S9 cofactor mixture dramatically decreased the cytotoxicity of S9, and (2) different S9 optimum concentrations were observed for struturally similar promutagens. The inclusion of CaCl/sub 2/ in the S9 cofactor mixture and the testing of each chemical of unknown S9 requirement at several S9 concentrations are therefore recommended for assaying promutagens in the CHO/HGPRT mutation assay.

  9. The Bombyx ovary-derived cell line endogenously expresses PIWI/PIWI-interacting RNA complexes.

    PubMed

    Kawaoka, Shinpei; Hayashi, Nobumitsu; Suzuki, Yutaka; Abe, Hiroaki; Sugano, Sumio; Tomari, Yukihide; Shimada, Toru; Katsuma, Susumu

    2009-07-01

    Genetic studies and large-scale sequencing experiments have revealed that the PIWI subfamily proteins and PIWI-interacting RNAs (piRNAs) play an important role in germ line development and transposon control. Biochemical studies in vitro have greatly contributed to the understanding of small interfering RNA (siRNA) and microRNA (miRNA) pathways. However, in vitro analyses of the piRNA pathway have been thus far quite challenging, because their expression is largely restricted to the germ line. Here we report that Bombyx mori ovary-derived cultured cell line, BmN4, endogenously expresses two PIWI subfamily proteins, silkworm Piwi (Siwi) and Ago3 (BmAgo3), and piRNAs associated with them. Siwi-bound piRNAs have a strong bias for uridine at their 5' end and BmAgo3-bound piRNAs are enriched for adenine at position 10. In addition, Siwi preferentially binds antisense piRNAs, whereas BmAgo3 binds sense piRNAs. Moreover, we identified many pairs in which Siwi-bound antisense and BmAgo3-bound sense piRNAs are overlapped by precisely 10 nt at their 5' ends. These signatures are known to be important for secondary piRNA biogenesis in other organisms. Taken together, BmN4 is a unique cell line in which both primary and secondary steps of piRNA biogenesis pathways are active. This cell line would provide useful tools for analysis of piRNA biogenesis and function. PMID:19460866

  10. Effects of different cryoprotectant combinations on primordial follicle survivability and apoptosis incidence after vitrification of whole rat ovary.

    PubMed

    Fathi, R; Valojerdi, M R; Salehnia, M

    2013-01-01

    This study was aimed at obtaining best vitrification conditions for preservation of primordial follicles after vitrification of whole ovarian tissue of rats. Ovaries of prepubertal ~5-week old female Wistar rats were divided randomly into 7 groups: Control (non-vitrified), V1 (EG+DMSO), V2 (EG+PROH), V3 (DMSO+PROH), V4 (EG+DMSO+Sucrose), V5 (EG+PROH+Sucrose) and V6 (DMSO+PROH+Sucrose). Control and vitrified-warmed samples were sectioned serially and stained either with HE or anti and pro active caspase-3 kit. The number of intact follicles in different stages of development was lower and the number of atretic and apoptotic follicles was higher in vitrification groups than those of the control group. Cryoprotectant combinations in V4 group showed better follicular preservation especially for primordial follicle. V3, V4 and V5 were best cryoprotectant mixtures, after the control group, according to the number of atretic follicles but the incidence of apoptotic primordial follicles was lowest in V3, V4 and V6. Incidence of apoptosis and the number of atretic follicles were lowest in V3 and V4 groups, and there was better primordial follicle preservation and survivability in VIV group. Thus, the combination of EG + DMSO with sucrose appears to be better suited for vitrification of whole ovarian tissue of rats. PMID:23812312

  11. Initiation of delayed ovotoxicity by in vitro and in vivo exposures of rat ovaries to 4-vinylcyclohexene diepoxide.

    PubMed

    Devine, Patrick J; Sipes, I Glenn; Hoyer, Patricia B

    2004-11-01

    Repeated daily dosing of rats with the ovotoxic, occupational chemical 4-vinylcyclohexene diepoxide (VCD, 80 mg/kg, i.p.) selectively depletes primordial and primary ovarian follicles. This study was designed to investigate whether follicle loss can be achieved following a single, acute exposure to VCD. Ovaries removed from postnatal-day-4 female Fischer 344 rats were cultured in the absence or presence of VCD for 15 days. Continuous in vitro exposure to VCD (15 days) caused concentration-dependent loss of primordial and small primary follicles. A single exposure to VCD in vitro (30 microM, 24 h) also caused significant losses of primordial and primary follicles 14 days later. Additionally, 28-day-old female rats were given a single injection of VCD (40-320 mg/kg, i.p.). A single dose at 320 mg/kg resulted in substantial loss of all follicle stages beginning 6 days later. Overall, these results demonstrate that an acute exposure to high concentrations/doses of VCD is sufficient to cause subsequent delayed loss of follicles. PMID:15336714

  12. 7,12-Dimethylbenz[a]anthracene exposure induces the DNA repair response in neonatal rat ovaries

    PubMed Central

    Ganesan, Shanthi; Bhattacharya, Poulomi; Keating, Aileen F.

    2013-01-01

    7,12-Dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles at all stages of development. This study investigated DMBA-induced DNA double strand break (DSB) formation with subsequent activation of the ovarian DNA repair response in models of pre-antral or pre-ovulatory follicle loss. Postnatal day (PND) 4 Fisher 344 (F344) rat ovaries were cultured for 4 days followed by single exposures of vehicle control (1% DMSO) or DMBA (12.5 nM or 75 nM) and maintained in culture for 4 or 8 days. Alternately, PND4 F344 rat ovaries were exposed to 1 µM DMBA at the start of culture for 2 days. Total RNA or protein was isolated, followed by qPCR or Western blotting to quantify mRNA or protein level, respectively. γH2AX and phosphorylated ATM were localized and quantified using immunofluorescence staining. DMBA exposure increased caspase 3 and γH2AX protein. Additionally, DMBA (12.5 nM and 1 µM) increased levels of mRNA encoding Atm, Xrcc6, Brca1 and Rad51. In contrast, Parp1 mRNA was decreased on d4 and increased on d8 of DMBA exposure, while PARP1 protein increased after 8 days of DMBA exposure. Total ATM increased in a concentration-dependent temporal pattern (75 nMd4; 12.5 nMd8), while pATM was localized in large primary and secondary follicles and increased after 8 days of 75 nM DMBA exposure compared to both control and 12.5 nM DMBA. These findings support that, despite some concentration effects, DMBA induces ovarian DNA damage and that DNA repair mechanisms are induced as a potential mechanism to prevent follicle loss. PMID:23969067

  13. Predominant role of the hypothalamic-pituitary axis, not the ovary, in different types of abnormal cycle induction by postnatal exposure to high dose p-tert-octylphenol in rats.

    PubMed

    Yoshida, Midori; Katashima, Sayumi; Tahahashi, Miwa; Ichimura, Ryohei; Inoue, Kaoru; Taya, Kazuyoshi; Watanabe, Gen

    2015-11-01

    To determine whether it is the hypothalamic-pituitary axis or the ovary that plays the predominant role in abnormal estrous cycling induction by postnatal exposure to estrogenic compounds, female rats were subcutaneously injected with 100mg/kg p-tert-octylphenol or vehicle for 5 or 15 days after birth (OP-PND5, OP-PND15 or control). Ovaries were exchanged between control and treated groups on PND28. Controls receiving control or OP-PND5 ovaries showed normal cycles within 4 weeks after the exchange, and corpora lutea were detected in transplanted ovaries. Controls receiving OP-PND15 ovaries consistently increased persistent estrus (PE). OP-PND15 rats receiving control or OP-PND15 ovaries immediately descended into PE, and transplanted ovaries were atrophic with cystic follicles, indicating anovulation. OP-PND5 rats receiving control or OP-PND5 ovaries showed early onset of PE after normal cycling. The hypothalamic-pituitary axis is predominant in abnormal cycling induction by postnatal exposure to OP. OP-PND15 ovaries were impaired compared to other groups. PMID:25975844

  14. 7,12-Dimethylbenz[a]anthracene exposure induces the DNA repair response in neonatal rat ovaries

    SciTech Connect

    Ganesan, Shanthi Bhattacharya, Poulomi Keating, Aileen F.

    2013-11-01

    7,12-Dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles at all stages of development. This study investigated DMBA-induced DNA double strand break (DSB) formation with subsequent activation of the ovarian DNA repair response in models of pre-antral or pre-ovulatory follicle loss. Postnatal day (PND) 4 Fisher 344 (F344) rat ovaries were cultured for 4 days followed by single exposures of vehicle control (1% DMSO) or DMBA (12.5 nM or 75 nM) and maintained in culture for 4 or 8 days. Alternately, PND4 F344 rat ovaries were exposed to 1 μM DMBA at the start of culture for 2 days. Total RNA or protein was isolated, followed by qPCR or Western blotting to quantify mRNA or protein level, respectively. γH2AX and phosphorylated ATM were localized and quantified using immunofluorescence staining. DMBA exposure increased caspase 3 and γH2AX protein. Additionally, DMBA (12.5 nM and 1 μM) increased levels of mRNA encoding Atm, Xrcc6, Brca1 and Rad51. In contrast, Parp1 mRNA was decreased on d4 and increased on d8 of DMBA exposure, while PARP1 protein increased after 8 days of DMBA exposure. Total ATM increased in a concentration-dependent temporal pattern (75 nM d4; 12.5 nM d8), while pATM was localized in large primary and secondary follicles and increased after 8 days of 75 nM DMBA exposure compared to both control and 12.5 nM DMBA. These findings support that, despite some concentration effects, DMBA induces ovarian DNA damage and that DNA repair mechanisms are induced as a potential mechanism to prevent follicle loss. - Highlights: • DMBA exposure increases ovarian caspase-3 protein expression. • DMBA exposure increases the γH2AX protein in oocytes. • DMBA exposure activates a DNA repair response in the ovary.

  15. Impact of 7,12-dimethylbenz[a]anthracene exposure on connexin gap junction proteins in cultured rat ovaries

    PubMed Central

    Ganesan, Shanthi; Keating, Aileen F.

    2014-01-01

    7,12-dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles in a concentration-dependent manner. The impact of DMBA on connexin (CX) proteins that mediate communication between follicular cell types along with pro-apoptotic factors p53 and Bax were investigated. Postnatal day (PND) 4 Fisher 344 rat ovaries were cultured for 4 days in vehicle medium (1% DMSO) followed by a single exposure to vehicle control (1% DMSO) or DMBA (12.5 nM or 75 nM) and cultured for 4 or 8 days. RT-PCR was performed to quantify Cx37, Cx43, p53 and Bax mRNA level. Western blotting and immunofluorescence staining were performed to determine CX37 or CX43 level and/or localization. Cx37 mRNA and protein increased (P < 0.05) at 4 days of 12.5 nM DMBA exposure. Relative to vehicle control-treated ovaries, mRNA encoding Cx43 decreased (P < 0.05) but CX43 protein increased (P < 0.05) at 4 days by both DMBA exposures. mRNA expression of pro-apoptotic p53 was decreased (P < 0.05) but no changes in Bax expression were observed after 4 days of DMBA exposures. In contrast, after 8 days, DMBA decreased Cx37 and Cx43 mRNA and protein but increased both p53 and Bax mRNA levels. CX43 protein was located between granulosa cells, while CX37 was located at the oocyte cell surface of all follicle stages. These findings support that DMBA exposure impacts ovarian Cx37 and Cx43 mRNA and protein prior to both observed changes in pro-apoptotic p53 and Bax and follicle loss. It is possible that such interference in follicular cell communication is detrimental to follicle viability, and may play a role in DMBA-induced follicular atresia. PMID:24269759

  16. Hormonal and metabolic effects of polyunsaturated fatty acid (omega-3) on polycystic ovary syndrome induced rats under diet

    PubMed Central

    Ouladsahebmadarek, Elaheh; Khaki, Arash; Khanahmadi, Sharareh; Ahmadi Ashtiani, Hamidreza; Paknejad, Pooya; Ayubi, Mohammad Reza

    2014-01-01

    Objective(s): PCOS (polycystic ovary syndrome) produces symptoms in approximately 5% to 10% of women of reproductive age (12–45 years old). It is thought to be one of the leading causes of female subfertility. This study aimed to confirm the role of nutrition containing omega-3 (polyunsaturated fatty acid) on control of experimental PCO induced by estradiol-valerat in rats. Materials and Methods: Wistar female rats (n=40) were allocated into control (n=10) and test groups (n= 30), test group was subdivided into 3 groups: G1, received omega-3 (240 mg/kg/orally/daily); G2 and G3 groups were induced PCO by single injection of estradiol-valerate (16 mg/kg/IM). Group 3 received omega-3 (240 mg/kg/orally/daily) and low carbohydrate feeding for 60 subsequent days; on sixtieth day 5 ml blood samples and ovarian tissues of all rats in the group were removed and prepared for biochemical and hormonal analysis. Results: Catalase, GPX (Glutathione peroxidase), SOD (Superoxide dismutase) in groups that received omega-3 showed higher levels, but MDA (malondialdehyde) level was significantly decreased (P<0.05) in comparison with other experimental groups. Ovarian weights in both experimental and control groups were similar (P<0.05). Level of serum FSH (follicle stimulating hormone) was decreased, but level of testosterone was significantly increased (P<0.05) in PCO group in comparison with control and omega-3 groups. Conclusion: Results revealed that administration of omega-3 plus lower carbohydrate food significantly controlled   PCO syndrome and balanced FSH and testosterone. PMID:24711896

  17. Central leptin resistance and hypothalamic inflammation are involved in letrozole-induced polycystic ovary syndrome rats.

    PubMed

    Lian, Yuling; Zhao, Fangui; Wang, Wenjun

    2016-08-01

    Accumulating evidence indicates that leptin acts as an important mediator in energy homeostasis and reproduction. Since dysfunction of reproduction and metabolism are major characteristics of polycystic ovarian syndrome (PCOS), the role of leptin in pathogenesis of PCOS needs further research. Many studies have shown that central leptin resistance existed in obesity rats through leptin intracerebroventricular (icv) injection; however, central leptin resistance in PCOS rats has not been reported. This study aimed to investigate whether there was a state of central leptin resistance in PCOS rats, as well as explore the possible association of hypothalamic inflammation with central leptin resistance. First, letrozole was used to induce the PCOS model, 24 h food intake, 24 h body weight changes and the expression of p-STAT3 were determined following leptin or artificial cerebrospinal fluid (aCSF) icv injection in rats. Second, we further evaluated the expressions of IL-1β, IL-6, TNF-α, p-IKKβ, NF-κB, p-NF-κB, IκBα, p-IκBα and SOCS3 in hypothalamus. The results showed that 24 h food intake and body weight were decreased, while the expression of p-STAT3 was increased in control group rats following leptin icv injection compared with aCSF icv injection; however, both of them showed no significant difference in PCOS rats. Furthermore, inflammatory markers were upregulated in the hypothalami of PCOS rats. Taken together, our data indicated that there was a state of chronic low-grade inflammation in hypothalamus which might be the possible mechanism for central leptin resistance in PCOS rats. PMID:27233601

  18. [Influence of stimulation and blockade of α4β2 nicotinic acetylcholine receptors on learning of female rats in basic phases of ovary cycle].

    PubMed

    Fedotova, Iu O

    2014-03-01

    The present work was devoted to the comparative analysis of α4β2 nicotinic acetylcholine receptors (nAChRs) in learning/memory processes during ovary cycle in the adult female rats. RJR-2403 (1.0 mg/kg, i. p.), α4β2 nAChRs agonist and mecamylamine (1.0 mg/kg, i. p.), α4β2 nAChRs antagonist were injected chronically during 14 days. The processes of learning/memory were assessed in different models of learning: passive avoidance performance and Morris water maze. Chronic RJR-2403 administration to females improved the passive avoidance performance in proestrous and estrous as compared to the control animals. Also, RJR-2403 restored spatial learning of rats during proestrous phases in Morris water maze, and stimulated the dynamics of spatial learning during estrous phases. On the contrary, the chronic mecamylamine administration impaired non-spatial, and especially, spatial learning in females during key phases of ovary cycle. The results of the study suggest positive effect of α4β2 nAChRs stimulation in learning/memory processes during ovary cycle in the adult female rats. PMID:25464732

  19. Metabolic, Behavioral and Reproductive Effects of Vertical Sleeve Gastrectomy in an Obese Rat Model of Polycystic Ovary Syndrome

    PubMed Central

    Ressler, Ilana B.; Grayson, Bernadette E.; Seeley, Randy J.

    2014-01-01

    Introduction Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age. Its clinical expression is diverse, including metabolic, behavioral and reproductive effects, with many affected by obesity and decreased quality of life. Women with PCOS who have undergone surgically-induced weight loss have reported tremendous benefit, not only with weight loss, but also improvement of hyperandrogenism and menstrual cyclicity. Methods In a rat model of PCOS achieved via chronic administration of dihydrotestosterone (DHT) exposure, we investigated the ability of bariatric surgery, specifically vertical sleeve gastrectomy (VSG), to ameliorate the metabolic, behavioral and reproductive abnormalities invoked by this PCOS model. Results We found that DHT-treatment combined with exposure to a high-fat diet resulted in increased body weight and body fat, impaired fasting glucose, hirsutism, anxiety and irregular cycles. VSG resulted in reduced food intake, body weight and adiposity with improved fasting glucose and triglycerides. VSG induced lower basal corticosterone levels and attenuated stress responsivity. Once the DHT levels decreased to normal, regular estrous cyclicity was also restored. Conclusion VSG, therefore, improved PCOS manifestations in a comprehensive manner and may represent a potential therapeutic approach for specific aspects of PCOS. PMID:24408363

  20. Regulation of NGFI-B/Nur77 gene expression in the rat ovary and in leydig tumor cells MA-10.

    PubMed

    Inaoka, Yoshihiko; Yazawa, Takashi; Uesaka, Miki; Mizutani, Tetsuya; Yamada, Kazuya; Miyamoto, Kaoru

    2008-05-01

    NR4A1, also called NGFI-B in the rat, Nur77 in the mouse and TR3 in humans, belongs to the orphan nuclear steroid hormone receptor superfamily and is one of the immediate-early genes. In the endocrine organs, including the gonads, NGFI-B/Nur77 gene expression is rapidly induced by pituitary hormones. NGFI-B/Nur77 expression was found to be rapidly reduced by an estrogenic endocrine disrupter, diethylstilbestrol (DES) in theca interna cells of immature rat ovaries. DES treatment also triggered a rapid decrease of serum luteinizing hormone (LH) levels, suggesting that DES acts on the hypothalamo-pituitary axis to suppress LH secretion from the pituitary. The transcriptional regulation of NGFI-B/Nur77 by LH/human chorionic gonadotropin (hCG) or 8-bromoadenosine 3'-5'-cyclic monophosphate (8 Br-cAMP) was examined in mouse Leydig tumor cells MA-10. Luciferase assays using NGFI-B/Nur77 promoter constructs and electric mobility shift assays (EMSA) showed that NGFI-B/Nur77 gene expression was mediated through three of the four activator protein-1 (AP-1)-like sites, namely the -233 AP-1, -213 AP-1 and -69 AP-1 sites adjacent to the transcription start site of the NGFI-B/Nur77 promoter. We also demonstrated here that both the Jun family and cAMP-responsive element binding (CREB) proteins bind to the -233 AP-1 site, whereas the main binding protein to the -213 AP-1 site was CREB, and Jun family protein to the -69 AP-1 site, respectively. The rapid induction of NGFI-B/Nur77 gene expression by LH/hCG in MA-10 cells appears to be mediated by both CREB and Jun family proteins through the cAMP-protein kinase A (PKA) pathway. PMID:18163434

  1. Protective effect of vitamin E on cypermethrin-induced follicular atresia in rat ovary: Evidence for energy dependent mechanism.

    PubMed

    Molavi, Morteza; Razi, Mazdak; Cheraghi, Hadi; Khorramjouy, Mona; Ostadi, Araz; Gholirad, Safa

    2016-01-01

    It has been shown that chronic exposure to cypermethrin (CPM), a pyrethroid pesticide, results in follicular atresia via pathologically affecting angiogenesis, disrupting endocrine potential and enhancing oxidative stress. This study was aimed to uncover the CPM-exposed energy dependent follicular cells apoptosis and to estimate protective effect of vitamin E (VitE) as a potent antioxidant. Thirty six Wistar rats were divided into six groups (n = 6 rats for each group) including; control-sham, CPM-received (CPM, 75 mg kg(-1), intraperitoneally), and CPM and VitE-treated (VitE, 150 mg kg(-1), orally) for 14 and 24 days. The protein biosynthesis of glucose transporter-1 (GLUT-1) and caspase-3 in follicles were estimated by using immuno-histochemical staining at preantral and antral stages. Moreover, the periodic acid Schiff (PAS) staining was performed in order to evaluate the intracytoplasmic carbohydrate ratio in follicular cells and oocyte. Percentages of follicles with GLUT-1, Caspase-3 and PAS-positive cells were compared between groups. Immunohistochemical analyses showed that, VitE significantly up-regulated the GLUT-1 expression and improved the intracytoplasmic carbohydrate supplementation especially at preantral follicles. The cross sections from the CPM-exposed ovaries represented remarkable elevation in percentage of atretic preantral and antral follicles with caspase-3 biosynthesis, which was remarkably (p < 0.05) diminished in VitE co-treated groups. In conclusion, our data showed that VitE by up-regulating of the GLUT-1 biosynthesis improved glucose uptake at follicular cells and oocyte levels that in turn inhibited pro-apoptotic protein caspase-3 biosynthesis. PMID:27482357

  2. Evidence for monomeric and oligomeric hormone-binding domains in affinity-purified gonadotropin receptor from rat ovary

    SciTech Connect

    Zhang, Q.Y.; Menon, K.M.J. )

    1989-11-01

    Rat ovarian lutropin/choriogonadotropin receptor was purified from a Triton X-100-solubilized membrane preparation by affinity chromatography with Affi-Gel 10 coupled to purified human choriogonadotropin. The affinity-purified receptor preparations contained a single class of high-affinity binding sites for {sup 125}I-labeled human choriogonadotropin, with an equilibrium dissociation constant (K{sub d}) of 2.5 {times} 10{sup {minus}9} M, which is comparable to the K{sub d} values for membrane-bound and solubilized receptors. The purified receptor appeared as two dominant bands with molecular weights of 135,000 and 92,000 after sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) under nonreducing conditions. When the individual affinity-purified receptor bands were electroeluted from the gel and analyzed again by SDS/PAGE under nonreducing conditions, both the M{sub r} 92,000 and the 135,000 proteins retained their original molecular form even when 8 M urea was included in the gel. However, when the electrophoretically purified M{sub r} 92,000 and 135,000 bands were subjected to SDS/PAGE under reducing conditions, the M{sub r} 135,000 species was almost completely converted to a M{sub r} 92,000 band, but the M{sub r} 92,000 species did not undergo any alteration in molecular weight. The results suggest that the lutropin/choriogonadotropin receptor from rat ovary exists in two molecular forms, and the higher molecular weight form appears to be composed of disulfide-linked M{sup r} 92,000 subunit, which comprises the hormone-binding domain.

  3. Protective effect of vitamin E on cypermethrin-induced follicular atresia in rat ovary: Evidence for energy dependent mechanism

    PubMed Central

    Molavi, Morteza; Razi, Mazdak; Cheraghi, Hadi; Khorramjouy, Mona; Ostadi, Araz; Gholirad, Safa

    2016-01-01

    It has been shown that chronic exposure to cypermethrin (CPM), a pyrethroid pesticide, results in follicular atresia via pathologically affecting angiogenesis, disrupting endocrine potential and enhancing oxidative stress. This study was aimed to uncover the CPM-exposed energy dependent follicular cells apoptosis and to estimate protective effect of vitamin E (VitE) as a potent antioxidant. Thirty six Wistar rats were divided into six groups (n = 6 rats for each group) including; control-sham, CPM-received (CPM, 75 mg kg-1, intraperitoneally), and CPM and VitE-treated (VitE, 150 mg kg-1, orally) for 14 and 24 days. The protein biosynthesis of glucose transporter-1 (GLUT-1) and caspase-3 in follicles were estimated by using immuno-histochemical staining at preantral and antral stages. Moreover, the periodic acid Schiff (PAS) staining was performed in order to evaluate the intracytoplasmic carbohydrate ratio in follicular cells and oocyte. Percentages of follicles with GLUT-1, Caspase-3 and PAS-positive cells were compared between groups. Immunohistochemical analyses showed that, VitE significantly up-regulated the GLUT-1 expression and improved the intracytoplasmic carbohydrate supplementation especially at preantral follicles. The cross sections from the CPM-exposed ovaries represented remarkable elevation in percentage of atretic preantral and antral follicles with caspase-3 biosynthesis, which was remarkably (p < 0.05) diminished in VitE co-treated groups. In conclusion, our data showed that VitE by up-regulating of the GLUT-1 biosynthesis improved glucose uptake at follicular cells and oocyte levels that in turn inhibited pro-apoptotic protein caspase-3 biosynthesis. PMID:27482357

  4. Roles of thyroid hormones in follicular development in the ovary of neonatal and immature rats.

    PubMed

    Fedail, Jaafar Sulieman; Zheng, Kaizhi; Wei, Quanwei; Kong, Lingfa; Shi, Fangxiong

    2014-08-01

    Thyroid hormones (TH) play a critical role in ovarian follicular development, maturation and the maintenance of various endocrine functions. However, whether TH can affect ovarian follicular development in neonatal and immature rats remains unclear. Therefore, the aim of the present study was to elucidate the effect of TH on ovarian follicular development in neonatal and immature rats. Thirty female post-lactation mothers of Sprague-Dawley rat pups were randomly divided into three groups: control, hyperthyroid (hyper), and hypothyroid (hypo). On postnatal days (PND) 10 and 21, body weights, serum hormones, ovarian histologic changes, and immunohistochemistry of thyroid hormone receptor alpha 1 (TRα1) and nitric oxide synthase types (NOS), and NOS activities, were determined. The data showed that body weights significantly decreased in both hyper and hypo groups compared with the control group (P < 0.05). In addition, the hyper group had increased serum concentrations of T3, T4, and E2; whereas the hypo group manifested reduced serum concentrations of T3, T4, and E2 on PND 10 and 21. The hyper and hypo groups showed significantly reduced total number of primordial, primary and secondary follicles on PND 10 and 21 compared with the control group (P < 0.05). Similarly, antral follicle numbers in the hyper and hypo groups were significantly decreased on PND 21 compared with the control group (P < 0.05). Immunostaining indicated that TRα1 and NOS were expressed in ovarian surface epithelium and oocytes of growing and antral follicles, with strong staining of the granulosa and theca cells of follicles. NOS activities were significantly augmented in the hyper, but diminished in the hypo groups on PND 10 and 21. In summary, our findings suggest that TH play important roles in ovarian functions and in the regulation of NOS activity. Our results also indicate that a relationship exists between the TH and NO signaling pathways during the process of ovarian follicular

  5. Impact of 7,12-dimethylbenz[a]anthracene exposure on connexin gap junction proteins in cultured rat ovaries

    SciTech Connect

    Ganesan, Shanthi Keating, Aileen F.

    2014-01-15

    7,12-Dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles in a concentration-dependent manner. The impact of DMBA on connexin (CX) proteins that mediate communication between follicular cell types along with pro-apoptotic factors p53 and Bax were investigated. Postnatal day (PND) 4 Fisher 344 rat ovaries were cultured for 4 days in vehicle medium (1% DMSO) followed by a single exposure to vehicle control (1% DMSO) or DMBA (12.5 nM or 75 nM) and cultured for 4 or 8 days. RT-PCR was performed to quantify Cx37, Cx43, p53 and Bax mRNA level. Western blotting and immunofluorescence staining were performed to determine CX37 or CX43 level and/or localization. Cx37 mRNA and protein increased (P < 0.05) at 4 days of 12.5 nM DMBA exposure. Relative to vehicle control-treated ovaries, mRNA encoding Cx43 decreased (P < 0.05) but CX43 protein increased (P < 0.05) at 4 days by both DMBA exposures. mRNA expression of pro-apoptotic p53 was decreased (P < 0.05) but no changes in Bax expression were observed after 4 days of DMBA exposures. In contrast, after 8 days, DMBA decreased Cx37 and Cx43 mRNA and protein but increased both p53 and Bax mRNA levels. CX43 protein was located between granulosa cells, while CX37 was located at the oocyte cell surface of all follicle stages. These findings support that DMBA exposure impacts ovarian Cx37 and Cx43 mRNA and protein prior to both observed changes in pro-apoptotic p53 and Bax and follicle loss. It is possible that such interference in follicular cell communication is detrimental to follicle viability, and may play a role in DMBA-induced follicular atresia. - Highlights: • DMBA increases Cx37 and Cx43 expression prior to follicle loss. • During follicle loss both Cx37 and Cx43 expressions are reduced. • CX43 protein is absent in follicle remnants lacking an oocyte.

  6. Effect of 4-vinylcyclohexene diepoxide dosing in rats on GSH levels in liver and ovaries.

    PubMed

    Devine, P J; Sipes, I G; Hoyer, P B

    2001-08-01

    Repeated daily dosing of rats with the occupational chemical 4- vinylcyclohexene or its diepoxide metabolite (VCD) for 15 days destroys the smallest ovarian follicles. VCD acutely reduced hepatic levels of the antioxidant, glutathione (GSH); therefore, these studies were designed to evaluate whether GSH concentrations mediate VCD-induced ovotoxicity. Immature female Fischer 344 rats were dosed once or daily for 15 days with VCD (0.57 mmol/kg, ip) or the GSH synthesis inhibitor buthionine sulfoximine (BSO, 2 mmol/kg, ip). Animals were euthanized 2, 6, or 26 h following a single dose, and 2 or 26 h following 15 days of daily dosing. Reduced (p < 0.05) hepatic GSH was seen within 2 h of a single dose of either VCD (51 +/- 5% of control) or BSO (42 +/- 9%), but only BSO reduced ovarian GSH (71 +/- 5% at 6 h, p = 0.05) as measured by HPLC. Within 26 h, GSH levels had returned to control levels with either treatment. Hepatic GSH levels were reduced (< 0.05) 2 h after 15 daily doses with BSO (42 +/- 5%) or VCD (70 +/- 4%), but only BSO decreased ovarian GSH (64 +/- 3%). GSH levels in 15-day tissues were similar to controls 26 h after the final dose. Neither BSO nor VCD increased hepatic or ovarian concentrations of the oxidized dimer of GSH (GSSG) or thiobarbituric acid-reactive substances (TBARS), indicators of oxidative stress. These results suggest these treatments did not cause an oxidative stress. Histological counts of ovarian small follicle numbers were reduced (p < 0.05) in 15-day VCD-treated rats, whereas BSO did not affect follicle numbers, even though BSO reduced ovarian GSH content. These results support the conclusion that alterations in ovarian GSH levels are not involved in VCD-induced ovotoxicity. PMID:11452144

  7. Behavior modulation of rats to a robotic rat in multi-rat interaction.

    PubMed

    Shi, Qing; Ishii, Hiroyuki; Tanaka, Katsuaki; Sugahara, Yusuke; Takanishi, Atsuo; Okabayashi, Satoshi; Huang, Qiang; Fukuda, Toshio

    2015-10-01

    In this paper, we study the behavioral response of rats to a robotic rat during multi-rat interaction. Experiments are conducted in an open-field where a robotic rat called WR-5 is put together with three laboratory rats. WR-5 is following one rat (target), while avoiding the other two rats (outside observers) during interaction. The behavioral characteristics of each target rat is evaluated by scoring its locomotor activity and frequencies of performing rearing, body grooming and mounting actions. Additionally, the frequency of being mounted by other rats is also measured. Experimental results show that the target becomes more active after interaction. The rat species, with more active behavioral characteristics, is more susceptible to being adjusted by the robot. The increased time spent by the outside observers in the vicinity of the robot indicates that a biomimetic robot has the promise for modulating rat behavior even without direct interaction. Thus, this study provide a novel approach to shaping the sociality of animals living in groups. PMID:26414400

  8. Neonatal exposure to estradiol-17β modulates tumour necrosis factor alpha and cyclooxygenase-2 expression in brain and also in ovaries of adult female rats.

    PubMed

    Shridharan, Radhika Nagamangalam; Krishnagiri, Harshini; Govindaraj, Vijayakumar; Sarangi, SitiKantha; Rao, Addicam Jagannadha

    2016-02-01

    The sexually dimorphic organization in perinatal rat brain is influenced by steroid hormones. Exposure to high levels of estrogen or endocrine-disrupting compounds during perinatal period may perturb this process, resulting in compromised reproductive physiology and behavior as observed in adult In our recent observation neonatal exposure of the female rats to estradiol-17β resulted in down-regulation of TNF-α, up-regulation of COX-2 and increase in SDN-POA size in pre-optic area in the adulthood. It is known that the control of reproductive performance in female involves a complex interplay of the hypothalamus, pituitary, and ovary. The present study was undertaken to understand the possible molecular mechanism involved in changes observed in the ovarian morphology and expression of selected genes in the ovary. Administration of estradiol-17β (100 μg) on day 2 and 3 after birth revealed up-regulation of ER-α, ER-β, COX-2 and down-regulation of TNF-α expression. Also the decrease in the ovarian weight, altered ovarian morphology and changes in the 2D protein profiles were also seen. This is apparently the first report documenting that neonatal estradiol exposure modulates TNF-α and COX-2 expression in the ovary as seen during adult stage. Our results permit us to suggest that cues originating from the modified brain structure due to neonatal exposure of estradiol-17β remodel the ovary at the molecular level in such a way that there is a disharmony in the reproductive function during adulthood and these changes are perennial and can lead to infertility and changes of reproductive behavior. PMID:26872318

  9. Inhibitory effect of leptin on the rat ovary during the ovulatory process.

    PubMed

    Ricci, A G; Di Yorio, M P; Faletti, A G

    2006-11-01

    The aims of this study were to investigate the negative action of leptin on some intraovarian ovulatory mediators during the ovulatory process and to assess whether leptin is able to alter the expression of its ovarian receptors. Immature rats primed with gonadotrophins were used to induce ovulation. Serum leptin concentration was diminished 4 h after human chorionic gonadotrophin (hCG) administration, whereas the ovarian expression of leptin receptors, measured by western blot, was increased by the gonadotrophin treatment. Serum progesterone level, ovulation rate and ovarian prostaglandin E (PGE) content were reduced in rats primed with equine chorionic gonadotrophin (eCG)/hCG and treated with acute doses of leptin (five doses of 5 mug each). These inhibitory effects were confirmed by in vitro studies, where the presence of leptin reduced the concentrations of progesterone, PGE and nitrites in the media of both ovarian explants and preovulatory follicle cultures. We also investigated whether these negative effects were mediated by changes in the expression of the ovarian leptin receptors. Since leptin treatment did not alter the expression of ovarian leptin receptor, the inhibitory effect of leptin on the ovulatory process may not be mediated by changes in the expression of its receptors at ovarian level, at least at the concentrations assayed. In summary, the ovulatory process was significantly inhibited in response to an acute treatment with leptin, and this effect may be due, at least in part, to the direct or indirect impairment of some ovarian factors, such as prostaglandins and nitric oxide. PMID:17071778

  10. Effect of electro-acupuncture on ovarian expression of α (1)- and β (2)-adrenoceptors, and p75 neurotrophin receptors in rats with steroid-induced polycystic ovaries

    PubMed Central

    Manni, Luigi; Lundeberg, Thomas; Holmäng, Agneta; Aloe, Luigi; Stener-Victorin, Elisabet

    2005-01-01

    Background Estradiol valerate (EV)-induced polycystic ovaries (PCO) in rats is associated with an increase in ovarian sympathetic outflow. Low-frequency (2 Hz) electro-acupuncture (EA) has been shown to modulate sympathetic markers as well as ovarian blood flow as a reflex response via the ovarian sympathetic nerves, in rats with EV-induced PCO. Methods In the present study, we further tested the hypothesis that repeated 2 Hz EA treatments modulate ovarian sympathetic outflow in rats with PCO, induced by a single i.m. injection of EV, by investigating the mRNA expression, the amount and distribution of proteins of α1a-, α1b-, α1d-, and β2-adrenoceptors (ARs), as well as the low-affinity neurotrophin receptor (p75NTR). Results It was found that EV injection results in significantly higher mRNA expression of ovarian α1b- and α1d-AR in PCO rats compared to control rats. The p75NTR and β2-ARs mRNA expression were unchanged in the PCO ovary. Low-frequency EA resulted in a significantly lower expression of β2-ARs mRNA expression in PCO rats. The p75NTR mRNA was unaffected in both PCO and control rats. PCO ovaries displayed significantly higher amount of protein of α1a-, α1b- and α1d-ARs, and of p75NTR, compared to control rats, that were all counteracted by repeated low-frequency EA treatments, except for α1b-AR. Conclusion The present study shows that EA normalizes most of the EV-induced changes in ovarian ARs. Furthermore, EA was able to prevent the EV-induced up regulation of p75NTR, probably by normalizing the sympathetic ovarian response to NGF action. Our data indicate a possible role of EA in the regulation of ovarian responsiveness to sympathetic inputs and depict a possible complementary therapeutic approach to overcoming sympathetic-related anovulation in women with PCOS. PMID:15941472

  11. HemoHIM improves ovarian morphology and decreases expression of nerve growth factor in rats with steroid-induced polycystic ovaries.

    PubMed

    Kim, Sung Ho; Lee, Hae June; Kim, Joong Sun; Moon, Changjong; Kim, Jong Choon; Bae, Chun Sik; Park, Hae Ran; Jung, Uhee; Jo, Sung Kee

    2009-12-01

    Estradiol valerate (EV)-induced polycystic ovaries (PCOs) in rats cause the anovulation and cystic ovarian morphology. We investigated whether treatment with HemoHIM influences the ovarian morphology and the expression of nerve growth factor (NGF) in an EV-induced PCO rat model. PCO was induced by a single intramuscular injection of EV (4 mg, dissolved in sesame oil) in adult cycling rats. HemoHIM was either administered orally (100 mg/kg of body weight/day) for 35 consecutive days or injected intraperitoneally (50 mg/kg of body weight) every other day after EV injection. Ovarian morphology was almost normalized, and NGF was normalized in the PCO + HemoHIM group. HemoHIM lowered the high numbers of antral follicles and increased the number of corpora lutea in PCOs. The results are consistent with a beneficial effect of HemoHIM in the prevention and treatment of PCO syndrome. PMID:20041792

  12. An imbalance between apoptosis and proliferation contributes to follicular persistence in polycystic ovaries in rats

    PubMed Central

    Salvetti, Natalia R; Panzani, Carolina G; Gimeno, Eduardo J; Neme, Leandro G; Alfaro, Natalia S; Ortega, Hugo H

    2009-01-01

    Background Cystic ovarian disease is an important cause of infertility that affects bovine, ovine, caprine and porcine species and even human beings. Alterations in the ovarian micro-environment of females with follicular cysts could alter the normal processes of proliferation and programmed cell death in ovarian cells. Thus, our objective was to evaluate apoptosis and proliferation in ovarian cystic follicles in rats in order to investigate the cause of cystic follicle formation and persistence. Methods We compared the number of in situ apoptotic cells by TUNEL assay, expression of active caspase-3 and members of Bcl-2 family by immunohistochemistry; and cell proliferation by the expression of the proliferation markers: PCNA and Ki-67. Results The proliferation index was low in granulosa of tertiary and cystic follicles of light exposed rats when compared with tertiary follicles of control animals, while in theca interna only cystic follicles presented low proliferation index when compared with tertiary follicles (p < 0.05). The granulosa of cysts exhibited a similar cell DNA fragmentation to early atretic follicles. In the granulosa and theca interna, active caspase-3 shown similar immunostaining levels in tertiary and cystic follicles (p < 0.05). The granulosa cells presented high expression of Bcl-2, Bcl-xL and Bcl-w in the tertiary and cystic follicles with diminishing intensity in the atretic follicles, except with Bcl-w where the intensity was maintained in the atretic follicles (p < 0.05). The expression of Bax was weak in the healthy and cystic follicles. In the theca interna, Bcl-2 expression was the same as the pattern found in the granulosa; no differences were found between tertiary and cystic follicles from both groups for Bcl-xL and Bcl-w. The expression of Bax in this layer was higher in the tertiary follicles of the treated animals (p < 0.05) while the values for cystic follicles were similar to those in the tertiary follicles of controls. The

  13. Local administration of platelet-derived growth factor B (PDGFB) improves follicular development and ovarian angiogenesis in a rat model of Polycystic Ovary Syndrome.

    PubMed

    Di Pietro, Mariana; Scotti, Leopoldina; Irusta, Griselda; Tesone, Marta; Parborell, Fernanda; Abramovich, Dalhia

    2016-09-15

    Alterations in ovarian angiogenesis are common features in Polycystic Ovary Syndrome (PCOS) patients; the most studied of these alterations is the increase in vascular endothelial growth factor (VEGF) production by ovarian cells. Platelet-derived growth factor B (PDGFB) and D (PDGFD) are decreased in follicular fluid of PCOS patients and in the ovaries of a rat model of PCOS. In the present study, we aimed to analyze the effects of local administration of PDGFB on ovarian angiogenesis, follicular development and ovulation in a DHEA-induced PCOS rat model. Ovarian PDGFB administration to PCOS rats partially restored follicular development, decreased the percentage of cysts, increased the percentage of corpora lutea, and decreased the production of anti-Müllerian hormone. In addition, PDGFB administration improved ovarian angiogenesis by reversing the increase in periendothelial cell area and restoring VEGF levels. Our results shed light into the mechanisms that lead to altered ovarian function in PCOS and provide new data for potential therapeutic strategies. PMID:27256152

  14. A single early postnatal estradiol injection affects morphology and gene expression of the ovary and parametrial adipose tissue in adult female rats.

    PubMed

    Alexanderson, Camilla; Stener-Victorin, Elisabet; Kullberg, Joel; Nilsson, Staffan; Levin, Max; Cajander, Stefan; Lönn, Lars; Lönn, Malin; Holmäng, Agneta

    2010-10-01

    Events during early life can affect reproductive and metabolic functions in adulthood. We evaluated the programming effects of a single early postnatal estradiol injection (within 3h after birth) in female rats. We assessed ovarian and parametrial adipose tissue morphology, evaluated gene expression related to follicular development and adipose tissue metabolism, and developed a non-invasive volumetric estimation of parametrial adipose tissue by magnetic resonance imaging. Estradiol reduced ovarian weight, increased antral follicle size and number of atretic antral follicles, and decreased theca interna thickness in atretic antral follicles. Adult estradiol-injected rats also had malformed vaginal openings and lacked corpora lutea, confirming anovulation. Estradiol markedly reduced parametrial adipose tissue mass. Adipocyte size was unchanged, suggesting reduced adipocyte number. Parametrial adipose tissue lipoprotein lipase activity was increased. In ovaries, estradiol increased mRNA expression of adiponectin, complement component 3, estrogen receptor α, and glucose transporter 3 and 4; in parametrial adipose tissue, expression of complement component 3 was increased, expression of estrogen receptor α was decreased, and expression of leptin, lipoprotein lipase, and hormone-sensitive lipase was unaffected. These findings suggest that early postnatal estradiol exposure of female rats result in long-lasting effects on the ovary and parametrial adipose tissue at adult age. PMID:19857573

  15. The effect of Non- ionizing electromagnetic field with a frequency of 50 Hz in Rat ovary: A transmission electron microscopy study

    PubMed Central

    Khaki, Amir Afshin; Khaki, Arash; Ahmadi, Seyed Shahin

    2016-01-01

    Background: Recently, there are increasing concerns and interests about the potential effects of Electromagnetic Field (EMF) on both human and animal health. Objective: The goal of this study was to evaluate the harmful effects of 50 Hz non-ionizing EMF on rat oocytes. Materials and Methods: In this experimental study 30 rats were randomly taken from laboratory animals and their ags and weights were determined. These 3 month's old rats were randomly divided into 3 groups. The control group consisted of 10 rats without receiving any treatment and kept under normal conditions. Experimental group 1 (10 rats) received EMF for 8 weeks (3 weeks intrauterine +5 weeks after births) and experimental group 2 (10 rats) received EMF for 13 weeks (3 weeks intrauterine +10 weeks after birth). After removing the ovaries and isolating follicles, granulosa cells were fixed in glutaraldehyde and osmium tetroxide. Electron microscopy was used to investigate the traumatic effects of EMF on follicles. Results: In control group nucleus membrane and mitochondria in follicle’s cytoplasm seemed normal in appearance. Theca layer of primary follicles in experimental group was separated clearly, zona layer demonstrated trot with irregular thickness and ovarian stroma seemed isolated with dilated vessels showing infiltration. Conclusion: According to the results of this study, it can be concluded that EMF has harmful effects on the ovarian follicles. PMID:27200427

  16. Continuous administration of a P450 aromatase inhibitor induces polycystic ovary syndrome with a metabolic and endocrine phenotype in female rats at adult age.

    PubMed

    Maliqueo, Manuel; Sun, Miao; Johansson, Julia; Benrick, Anna; Labrie, Fernand; Svensson, Henrik; Lönn, Malin; Duleba, Antoni J; Stener-Victorin, Elisabet

    2013-01-01

    Studying the mechanisms for the complex pathogenesis of polycystic ovary syndrome (PCOS) requires animal models with endocrine, reproductive, and metabolic features of the syndrome. Hyperandrogenism seems to be a central factor in PCOS, leading to anovulation and insulin resistance. In female rats, continuous administration of letrozole, a nonsteroidal inhibitor of P450 aromatase, at 400 μg/d starting before puberty induces hyperandrogenemia and reproductive abnormalities similar to those in women with PCOS. However, despite high circulating testosterone levels, these rats do not develop metabolic abnormalities, perhaps because of their supraphysiological testosterone concentrations or because estrogen synthesis is completely blocked in insulin-sensitive tissues. To test the hypothesis that continuous administration of lower doses of letrozole starting before puberty would result in both metabolic and reproductive phenotypes of PCOS, we performed a 12-wk dose-response study. At 21 d of age, 46 female Wistar rats were divided into two letrozole groups (100 or 200 μg/d) and a control group (placebo). Both letrozole doses resulted in increased body weight, inguinal fat accumulation, anovulation, larger ovaries with follicular atresia and multiples cysts, endogenous hyperandrogemia, and lower estrogen levels. Moreover, rats that received 200 μg/d had insulin resistance and enlarged adipocytes in inguinal and mesenteric fat depots, increased circulating levels of LH, decreased levels of FSH, and increased ovarian expression of Cyp17a1 mRNA. Thus, continuous administration of letrozole, 200 μg/d, to female rats for 90 d starting before puberty results in a PCOS model with reproductive and metabolic features of the syndrome. PMID:23183180

  17. Gender Differences in Transcriptional Signature of Developing Rat Testes and Ovaries following Embryonic Exposure to 2,3,7,8-TCDD

    PubMed Central

    Magre, Solange; Rebourcet, Diane; Ishaq, Muhammad; Wargnier, Richard; Debard, Cyrille; Meugnier, Emmanuelle; Vidal, Hubert; Cohen-Tannoudji, Joëlle; Le Magueresse-Battistoni, Brigitte

    2012-01-01

    Dioxins are persistent organic pollutants interfering with endocrine systems and causing reproductive and developmental disorders. The objective of our project was to determine the impact of an in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on reproductive function of male and female offspring in the rat with a special emphasis on the immature period. We used a low dose of TCDD (unique exposure by oral gavage of 200 ng/kg at 15.5 days of gestation) in order to mirror a response to an environmental dose of TCDD not altering fertility of the progeny. We choose a global gene expression approach using Affymetrix microarray analysis, and testes of 5 days and ovaries of 14 days of age. Less than 1% of the expressed genes in gonads were altered following embryonic TCDD exposure; specifically, 113 genes in ovaries and 56 in testes with 7 genes common to both sex gonads. It included the repressor of the aryl hydrocarbon receptor (Ahrr), the chemokines Ccl5 and Cxcl4 previously shown to be regulated by dioxin in testis, Pgds2/Hpgds and 3 others uncharacterized. To validate and extend the microarray data we realized real-time PCR on gonads at various developmental periods of interest (from 3 to 25 days for ovaries, from 5 to the adult age for testes). Overall, our results evidenced that both sex gonads responded differently to TCDD exposure. For example, we observed induction of the canonic battery of TCDD-induced genes coding enzymes of the detoxifying machinery in ovaries aged of 3–14 days of age (except Cyp1a1 induced at 3–10 days) but not in testes of 5 days (except Ahrr). We also illustrated that inflammatory pathway is one pathway activated by TCDD in gonads. Finally, we identified several new genes targeted by TCDD including Fgf13 in testis and one gene, Ptgds2/Hpgds regulated in the two sex gonads. PMID:22808131

  18. Electrical and manual acupuncture stimulation affect oestrous cyclicity and neuroendocrine function in an 5α-dihydrotestosterone-induced rat polycystic ovary syndrome model.

    PubMed

    Feng, Yi; Johansson, Julia; Shao, Ruijin; Mannerås-Holm, Louise; Billig, Håkan; Stener-Victorin, Elisabet

    2012-05-01

    Both low-frequency electro-acupuncture (EA) and manual acupuncture improve menstrual frequency and decrease circulating androgens in women with polycystic ovary syndrome (PCOS). We sought to determine whether low-frequency EA is more effective than manual stimulation in regulating disturbed oestrous cyclicity in rats with PCOS induced by 5α-dihydrotestosterone. To identify the central mechanisms of the effects of stimulation, we assessed hypothalamic mRNA expression of molecules that regulate reproductive and neuroendocrine function. From age 70 days, rats received 2 Hz EA or manual stimulation with the needles five times per week for 4-5 weeks; untreated rats served as control animals. Specific hypothalamic nuclei were obtained by laser microdissection, and mRNA expression was measured with TaqMan low-density arrays. Untreated rats were acyclic. During the last 2 weeks of treatment, seven of eight (88%) rats in the EA group had epithelial keratinocytes, demonstrating oestrous cycle change (P = 0.034 versus control rats). In the manual group, five of eight (62%) rats had oestrous cycle changes (n.s. versus control animals). The mRNA expression of the opioid receptors Oprk1 and Oprm1 in the hypothalamic arcuate nucleus was lower in the EA group than in untreated control rats. The mRNA expression of the steroid hormone receptors Esr2, Pgr and Kiss1r was lower in the manual group than in the control animals. In rats with 5α-dihydrotestosterone-induced PCOS, low-frequency EA restored disturbed oestrous cyclicity but did not differ from the manual stimulation group, although electrical stimulation lowered serum testosterone in responders, those with restored oestrus cyclicity, and differed from both control animals and the manual stimulation group. Thus, EA cannot in all aspects be considered superior to manual stimulation. The effects of low-frequency EA may be mediated by central opioid receptors, while manual stimulation may involve regulation of steroid hormone

  19. Effect of phosphatidylinositol-3 kinase inhibition on ovotoxicity caused by 4-vinylcyclohexene diepoxide and 7, 12-dimethylbenz[a]anthracene in neonatal rat ovaries

    SciTech Connect

    Keating, Aileen F.; Mark, Connie J.; Sen, Nivedita; Sipes, I. Glenn; Hoyer, Patricia B.

    2009-12-01

    4-vinylcyclohexene diepoxide (VCD) is an ovotoxicant that specifically destroys primordial and small primary follicles in the ovaries of mice and rats. In contrast, 7,12-dimethylbenz[a]anthracene (DMBA) is ovotoxic to all ovarian follicle classes. This study investigated phosphatidylinositol-3 kinase signaling involvement in VCD- and DMBA-induced ovotoxicity. Postnatal day (PND) 4 Fischer 344 (F344) rat whole ovaries were cultured for 2-12 days in vehicle control, VCD (30 muM), or DMBA (1 muM), +- PI3 kinase inhibitor LY294002 (20 muM) or its inactive analog LY303511 (20 muM). Following culture, ovaries were histologically evaluated, and healthy follicles were classified and counted. PI3 kinase inhibition had no effect on primordial follicle number, but reduced (P < 0.05) small primary and larger follicles beginning on day 4. VCD caused primordial and small primary follicle loss (P < 0.05) beginning on day 6. With PI3 kinase inhibition, VCD did not affect primordial follicles (P > 0.05) at any time, but did cause loss (P < 0.05) of small primary follicles. DMBA exposure caused primordial and small primary follicle loss (P < 0.05) on day 6. Further, DMBA-induced primordial and small primary follicle loss was greater with PI3 kinase inhibition (P < 0.05) than with DMBA alone. These results support that (1) PI3 kinase mediates primordial to small primary follicle recruitment, (2) VCD, but not DMBA, enhances ovotoxicity by increasing primordial to small primary follicle recruitment, and (3) in addition to xenobiotic-induced ovotoxicity, VCD is also a useful model chemical with which to elucidate signaling mechanisms involved in primordial follicle recruitment.

  20. Effect of phosphatidylinositol-3 kinase inhibition on ovotoxicity caused by 4-vinylcyclohexene diepoxide and 7, 12-dimethylbenz[a]anthracene in neonatal rat ovaries.

    PubMed

    Keating, Aileen F; J Mark, Connie; Sen, Nivedita; Sipes, I Glenn; Hoyer, Patricia B

    2009-12-01

    4-vinylcyclohexene diepoxide (VCD) is an ovotoxicant that specifically destroys primordial and small primary follicles in the ovaries of mice and rats. In contrast, 7,12-dimethylbenz[a]anthracene (DMBA) is ovotoxic to all ovarian follicle classes. This study investigated phosphatidylinositol-3 kinase signaling involvement in VCD- and DMBA-induced ovotoxicity. Postnatal day (PND) 4 Fischer 344 (F344) rat whole ovaries were cultured for 2-12 days in vehicle control, VCD (30 microM), or DMBA (1 microM), +/-PI3 kinase inhibitor LY294002 (20 microM) or its inactive analog LY303511 (20 microM). Following culture, ovaries were histologically evaluated, and healthy follicles were classified and counted. PI3 kinase inhibition had no effect on primordial follicle number, but reduced (P<0.05) small primary and larger follicles beginning on day 4. VCD caused primordial and small primary follicle loss (P<0.05) beginning on day 6. With PI3 kinase inhibition, VCD did not affect primordial follicles (P>0.05) at any time, but did cause loss (P<0.05) of small primary follicles. DMBA exposure caused primordial and small primary follicle loss (P<0.05) on day 6. Further, DMBA-induced primordial and small primary follicle loss was greater with PI3 kinase inhibition (P<0.05) than with DMBA alone. These results support that (1) PI3 kinase mediates primordial to small primary follicle recruitment, (2) VCD, but not DMBA, enhances ovotoxicity by increasing primordial to small primary follicle recruitment, and (3) in addition to xenobiotic-induced ovotoxicity, VCD is also a useful model chemical with which to elucidate signaling mechanisms involved in primordial follicle recruitment. PMID:19695275

  1. The use of primary rat hepatocytes to achieve metabolic activation of promutagens in the Chinese hamster ovary/hypoxantine-guanine phosphoribosyl transferase mutational assay

    SciTech Connect

    Bermudez, E.; Couch, D.B.; Tillery, D.

    1982-01-01

    A method is described in which primary rat hepatocytes have been cocultured with chinese hamster ovary (CHO) cells to provide metabolic activation of promutgens in the Chinese hamster ovary/hypoxanthine-guanine phosphoribosyl transferase (CHO/HGPRT) mutational assay. Single cell hepatocyte suspensions were prepared from male Fisher-344 rats using the in situ collagenase perfusion technique. Hepatocytes were allowed to attach for 1.5 hours in tissue culture dishes containing an approximately equal number of CHO cells in log growth. The cocultures were exposed to promutagens for up to 20 hours in serum-free medium. The survival and 6-thioguanine-resistant fraction of treated CHO cells were then determined as in the standard CHO/HGPRT assay. Aflatoxin B/sub 1/ (AFB/sub 1/) 7,12-dimethylbenz(a)anthracene (DMBA) and benzo(a)pyrene (B(a)P) were found to produce increases in the mutant fractions of treated CHO cells as a function of concentration. The time required for optimum expression of the mutant phenotype following exposure to DMBA and AFB/sub 1/ was approximately 8 days. Primary cell-mediated mutagenesis may be useful in elucidating methobolic pathways important in the production and detoxification of genotoxic products in vivo.

  2. CXCR4/SDF1 interaction inhibits the primordial to primary follicle transition in the neonatal mouse ovary.

    PubMed

    Holt, Janet E; Jackson, Andrew; Roman, Shaun D; Aitken, R John; Koopman, Peter; McLaughlin, Eileen A

    2006-05-15

    The molecular mechanisms behind the entry of the primordial follicle into the growing follicle pool remain poorly understood. To investigate this process further, a microarray-based comparison was undertaken between 2-day postpartum mouse ovaries consisting of primordial follicles/naked oocytes only and those with both primordial follicles and newly activated follicles (7-day postpartum). Gene candidates identified included the chemoattractive cytokine stromal derived factor-1 (SDF1) and its receptor CXCR4. SDF1 and CXCR4 have been implicated in a variety of physiological processes including the migration of embryonic germ cells to the gonads. SDF1-alpha expression increased with the developmental stage of the follicle. Embryonic expression was found to be dichotomous post-germ cell migration, with low expression in the female. Immunohistochemical studies nonetheless indicate that the autocrine pattern of expression ligand and receptor begins during embryonic life. Addition of recombinant SDF1-alpha to neonatal mouse ovaries in vitro resulted in significantly higher follicle densities than for control ovaries. TUNEL analysis indicated no detectable difference in populations of apoptotic cells of treated or control ovaries. Treated ovaries also contained a significantly lower percentage of activated follicles as determined by measurement of oocyte diameter and morphological analysis. Treatment of cultured ovaries with an inhibitor of SDF1-alpha, AMD3100, ablated the effect of SDF1-alpha. By retaining follicles in an unactivated state, SDF1/CXCR4 signaling may play an important role in maintaining the size and longevity of the primordial follicle pool. PMID:16545793

  3. Intense electroacupuncture normalizes insulin sensitivity, increases muscle GLUT4 content, and improves lipid profile in a rat model of polycystic ovary syndrome.

    PubMed

    Johansson, Julia; Feng, Yi; Shao, Ruijin; Lönn, Malin; Billig, Håkan; Stener-Victorin, Elisabet

    2010-10-01

    Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and insulin resistance, possibly reflecting defects in skeletal muscle and adipocyte insulin signaling. Low-frequency (2 Hz) electroacupuncture (EA) increases insulin sensitivity in female rats with dihydrotestosterone (DHT)-induced PCOS, but the mechanism is unclear. We hypothesized that low-frequency EA regulates mediators involved in skeletal muscle glucose uptake and metabolism and alters the lipid profile in rats with DHT-induced PCOS. To test this hypothesis, we implanted in prepubescent female rats 90-day continuous-release pellets containing DHT (PCOS). At 70 days of age, the rats were randomly subdivided into two groups: one received low-frequency EA (evoking muscle twitches) for 20-25 min five times/wk for 4-5 wk; the other did not. Controls were implanted with pellets containing vehicle only. All three groups were otherwise handled similarly. Lipid profile was measured in fasting blood samples. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp, soleus muscle protein expression of glucose transporter 4 (GLUT4), and phosphorylated and nonphosphorylated Akt, and Akt substrate of 160 kDa was determined by Western blot analysis and GLUT4 location by immunofluorescence staining. PCOS EA rats had normalized insulin sensitivity, lower levels of total high-density lipoprotein and low-density lipoprotein cholesterol, and increased expression of GLUT4 in different compartments of skeletal muscle compared with PCOS rats. Total weight and body composition did not differ in the groups. Thus, in rats with DHT-induced PCOS, low-frequency EA has systemic and local effects involving intracellular signaling pathways in muscle that may, at least in part, account for the marked improved insulin sensitivity. PMID:20663984

  4. Interaction between succinylcholine and cimetidine in rats.

    PubMed

    Mishra, Y; Ramzan, I

    1992-04-01

    The hypothesis that histamine H2 receptor blockade adversely affects neuromuscular function was tested, in vivo, in rats anaesthetised with urethane during mechanical pulmonary ventilation. Succinylcholine was administered as a bolus and constant-rate infusion to maintain 49.2% (+/- 1.5 SEM) twitch suppression in 19 rats. Cimetidine iv, 3.2, 7.5, 10, 17.8, 23.7, 31.6, or 56.2 mg.kg-1 was then administered in groups of two to three rats. Cimetidine produced an immediate potentiation of twitch suppression followed by a transient reversal and then a continued potentiation. Peak potentiation occurred within 19.0 (+/- 2.7) sec and was maintained in 11 rats at steady-state. Reversal was evident 4.1 (+/- 0.4) min after cimetidine administration. There was a good relationship between peak potentiation and serum cimetidine concentration with 50% potentiation occurring at 46.5 (+/- 4.6) micrograms.ml-1. Potentiation at steady-state was not correlated to serum cimetidine concentration but there was a weak relationship between reversal and serum cimetidine concentration. These results support reports from patients of an interaction between cimetidine and succinylcholine. PMID:1314141

  5. Histopathologycal findings in the ovaries and uterus of albino female rats promoted by co-administration of synthetic steroids and nicotine.

    PubMed

    Camargo, Isabel Cristina Cherici; Leite, Gabriel Adan Araújo; Pinto, Tiago; Ribeiro-Paes, João Tadeu

    2014-07-01

    The use of anabolic androgenic steroids is often associated with the use of other substances, licit or not, such as nicotine present in the tobacco. The present study investigated for the first time the effects of co-administration of synthetic steroids and nicotine on the ovarian and uterine tissue and fertility of adult female rats. Animals were submitted to treatment groups (n=16/group): nandrolone decanoate (ND; 7.5mg/kg BW/week); testosterone mixture (T; 7.5mg/kg BW/week); nicotine (N; 2.0mg/kg BW/day), and co-administration of ND/N, T/N and ND/T/N. The control group received saline solution daily. The injections were administered subcutaneously for 30 consecutive days. Results demonstrated that all androgenized rats exhibited estral acyclicity and there was suppression of reproductive capacity due to notable ovarian and uterine histological changes. Treatments promoted decrease (p<0.05) in the ovarian weight. Uterine weight increased (p<0.05) in the T and T/N groups, in comparison to control group. ND or T co-administered or not to nicotine promoted intense follicular degeneration, with formation of cysts in the ovaries. High levels of circulating androgens in the ND/T/N group induced the presence of ovarian sex cord-stromal tumors of Sertoli cell pattern. Androgenized females presented endometrial changes characterized by papilliferous or pleated luminal epithelium, oedematous and hemorrhagic stroma and presence of gland cysts. In conclusion, the co-administration of three drugs promoted atypical morphological pattern on the ovaries and uterus of female rats. PMID:24556002

  6. The effect of metamizole on ischemia/reperfusion injury in the rat ovary: An analysis of biochemistry, molecular gene expression, and histopathology

    PubMed Central

    Kumbasar, Serkan; Salman, Suleyman; Al, Ragip Atakan; Ozturk, Cengiz; Yarali, Oguzhan; Alp, Hamit Hakan; Altuner, Durdu; Suleyman, Bahadir

    2016-01-01

    Objectives: In this study, we investigated the effect of metamizole on ischemia/reperfusion (I/R) injury an analysis of biochemistry, molecular gene expression, and histopathology in the rat ovary of female albino Wistar rats. Materials and Methods: Animals were divided into four groups; control group with induced ischemia-reperfusion (IRC), ischemia-reperfusion +100 mg/kg metamizole sodium (MS) (IRM-100), ischemia-reperfusion +200 mg/kg MS (IRM-200), and healthy group applied sham operation (SG). Results: Myeloperoxidase (MPO) activity and gene expression increased significantly in IRC and IRM-100 group rat ovarian tissue compared with the SG group (P < 0.0001). However, MPO activity and gene expression in IRM-200 group ovarian tissue decreased significantly compared with the IRC and IRM-100 groups (P < 0.0001). Histopathologically, pronounced congestion, dilated vessels, hemorrhage, edema, degenerative cells, and neutrophil migration and adhesion to the endothelium were observed in the IRC and IRM-100 group ovarian tissues. A small number of congested dilated vessels, mild congestion, and edema were observed in the IRM-200 group, but no neutrophil migration and adhesion to the endothelium or degenerative cells. Conclusions: At 200 mg/kg dose metamizole prevented ovarian injury induced with I/R. This data show that metamizole can be used in the ovarian I/R injury treatment. PMID:26997719

  7. Interactions between respiratory oscillators in adult rats

    PubMed Central

    Huckstepp, Robert TR; Henderson, Lauren E; Cardoza, Kathryn P; Feldman, Jack L

    2016-01-01

    Breathing in mammals is hypothesized to result from the interaction of two distinct oscillators: the preBötzinger Complex (preBötC) driving inspiration and the lateral parafacial region (pFL) driving active expiration. To understand the interactions between these oscillators, we independently altered their excitability in spontaneously breathing vagotomized urethane-anesthetized adult rats. Hyperpolarizing preBötC neurons decreased inspiratory activity and initiated active expiration, ultimately progressing to apnea, i.e., cessation of both inspiration and active expiration. Depolarizing pFL neurons produced active expiration at rest, but not when inspiratory activity was suppressed by hyperpolarizing preBötC neurons. We conclude that in anesthetized adult rats active expiration is driven by the pFL but requires an additional form of network excitation, i.e., ongoing rhythmic preBötC activity sufficient to drive inspiratory motor output or increased chemosensory drive. The organization of this coupled oscillator system, which is essential for life, may have implications for other neural networks that contain multiple rhythm/pattern generators. DOI: http://dx.doi.org/10.7554/eLife.14203.001 PMID:27300271

  8. Interactions between respiratory oscillators in adult rats.

    PubMed

    Huckstepp, Robert Tr; Henderson, Lauren E; Cardoza, Kathryn P; Feldman, Jack L

    2016-01-01

    Breathing in mammals is hypothesized to result from the interaction of two distinct oscillators: the preBötzinger Complex (preBötC) driving inspiration and the lateral parafacial region (pFL) driving active expiration. To understand the interactions between these oscillators, we independently altered their excitability in spontaneously breathing vagotomized urethane-anesthetized adult rats. Hyperpolarizing preBötC neurons decreased inspiratory activity and initiated active expiration, ultimately progressing to apnea, i.e., cessation of both inspiration and active expiration. Depolarizing pFL neurons produced active expiration at rest, but not when inspiratory activity was suppressed by hyperpolarizing preBötC neurons. We conclude that in anesthetized adult rats active expiration is driven by the pFL but requires an additional form of network excitation, i.e., ongoing rhythmic preBötC activity sufficient to drive inspiratory motor output or increased chemosensory drive. The organization of this coupled oscillator system, which is essential for life, may have implications for other neural networks that contain multiple rhythm/pattern generators. PMID:27300271

  9. Cognitive-impairing effects of medroxyprogesterone acetate in the rat: independent and interactive effects across time

    PubMed Central

    Braden, B. Blair; Garcia, Alexandra N.; Mennenga, Sarah E.; Prokai, Laszlo; Villa, Stephanie R.; Acosta, Jazmin I.; Lefort, Natalie; Simard, Alain R.

    2013-01-01

    Rationale The synthetic progestin medroxyprogesterone acetate (MPA), widely used in hormone therapy (HT) and as the contraceptive Depo Provera, is implicated in detrimental cognitive effects in women. Recent evidence in aged ovariectomized (Ovx) rodents shows that short-term MPA treatment impairs cognition and alters the GABAergic system. Objectives Using rats, we evaluated the long-lasting cognitive and GABAergic effects of MPA administered in young adulthood (Early-MPA), modeling contraception, and how this early exposure interacts with later MPA treatment (Late-MPA), modeling HT. Methods Early-MPA treatment involved weekly anti-ovulatory MPA injections (3.5 mg) from 4 to 8 months of age in ovary-intact rats. At 10 months old, rats were Ovx and weekly MPA injections were re-initiated and continued throughout testing for Late-MPA treatment. Results On the water radial-arm maze, all MPA-treated groups showed working memory impairment compared to Controls (p<0.05); Early+Late-MPA rats were impaired on multiple dimensions of working memory (p<0.05). On the Morris maze, Late-MPA rats showed greater overnight forgetting compared to Controls (p<0.05). At study conclusion, MPA was detected in serum in all MPA-treated groups except Early-MPA, confirming treatment and clearance from serum in Early-MPA rats. In animals with detectable serum MPA, higher MPA levels were associated with less dorsal-hippocampal glutamic acid decarboxylase, the synthesizing enzyme for GABA (p=0.0059). Conclusions Findings suggest that MPA treatment leads to long-lasting cognitive impairments in the rodent, even in the absence of circulating MPA in animals given prior MPA treatment, which may relate to the GABAergic system. Further research defining the parameters of the negative impact of this widely used progestin on brain and cognition is warranted. PMID:21562760

  10. Bisphenol A Exposure during Adulthood Causes Augmentation of Follicular Atresia and Luteal Regression by Decreasing 17β-Estradiol Synthesis via Downregulation of Aromatase in Rat Ovary

    PubMed Central

    Lee, Seung Gee; Chung, Jin-Yong; Park, Ji-Eun; Oh, Seunghoon; Yoon, Yong-Dal; Yoo, Ki Soo; Yoo, Young Hyun

    2013-01-01

    Background: Bisphenol A (BPA) has been detected in human body fluids, such as serum and ovarian follicular fluids. Several reports indicated that BPA exposure is associated with the occurrence of several female reproductive diseases resulting from the disruption of steroid hormone biosynthesis in the adult ovary. Objective: We hypothesized that long-term exposure to low concentrations of BPA disrupts 17β-estradiol (E2) production in granulosa cells via an alteration of steroidogenic proteins in ovarian cells. Methods: Adult female rats received BPA for 90 days by daily gavage at doses of 0, 0.001, or 0.1 mg/kg body weight. We determined serum levels of E2, testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). We also analyzed the expressions of steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage (P450scc), 3β-hydroxysteroid dehydrogenase isomerase (3β-HSD), and aromatase cytochrome P450 (P450arom) in the ovary. Results: Exposure to BPA significantly decreased E2 serum concentration, which was accompanied by augmented follicular atresia and luteal regression via increase of caspase-3–associated apoptosis in ovarian cells. After BPA exposure, P450arom and StAR protein levels were significantly decreased in granulosa cells and theca-interstitial (T-I) cells, respectively. However, P450scc and 3β-HSD protein levels remained unchanged. The increase in LH levels appeared to be associated with the decreased synthesis of T in T-I cells after BPA exposure via homeostatic positive feedback regulation. Conclusions: BPA exposure during adulthood can disturb the maintenance of normal ovarian functions by reducing E2. The steroidogenic proteins StAR and P450arom appear to be targeted by BPA. PMID:23512349

  11. Electrical vs manual acupuncture stimulation in a rat model of polycystic ovary syndrome: different effects on muscle and fat tissue insulin signaling.

    PubMed

    Johansson, Julia; Mannerås-Holm, Louise; Shao, Ruijin; Olsson, AnneLiese; Lönn, Malin; Billig, Håkan; Stener-Victorin, Elisabet

    2013-01-01

    In rats with dihydrotestosterone (DHT)-induced polycystic ovary syndrome (PCOS), repeated low-frequency electrical stimulation of acupuncture needles restores whole-body insulin sensitivity measured by euglycemic hyperinsulinemic clamp. We hypothesized that electrical stimulation causing muscle contractions and manual stimulation causing needle sensation have different effects on insulin sensitivity and related signaling pathways in skeletal muscle and adipose tissue, with electrical stimulation being more effective in DHT-induced PCOS rats. From age 70 days, rats received manual or low-frequency electrical stimulation of needles in abdominal and hind limb muscle five times/wk for 4-5 wks; controls were handled but untreated rats. Low-frequency electrical stimulation modified gene expression (decreased Tbc1d1 in soleus, increased Nr4a3 in mesenteric fat) and protein expression (increased pAS160/AS160, Nr4a3 and decreased GLUT4) by western blot and increased GLUT4 expression by immunohistochemistry in soleus muscle; glucose clearance during oral glucose tolerance tests was unaffected. Manual stimulation led to faster glucose clearance and modified mainly gene expression in mesenteric adipose tissue (increased Nr4a3, Mapk3/Erk, Adcy3, Gsk3b), but not protein expression to the same extent; however, Nr4a3 was reduced in soleus muscle. The novel finding is that electrical and manual muscle stimulation affect glucose homeostasis in DHT-induced PCOS rats through different mechanisms. Repeated electrical stimulation regulated key functional molecular pathways important for insulin sensitivity in soleus muscle and mesenteric adipose tissue to a larger extent than manual stimulation. Manual stimulation improved whole-body glucose tolerance, an effect not observed after electrical stimulation, but did not affect molecular signaling pathways to the same extent as electrical stimulation. Although more functional signaling pathways related to insulin sensitivity were affected by

  12. Controlled reperfusion for different durations in the treatment of ischemia-reperfusion injury of the rat ovary: evaluation of biochemical features, molecular gene expression, and histopathology.

    PubMed

    Yapca, Omer Erkan; Kumbasar, Serkan; Salman, Suleyman; Yarali, Oguzhan; Sener, Ebru; Mammadov, Renad; Tekin, Yesim Bayoglu; Aksoy, Aysenur; Albayrak, Abdulmecit; Cetin, Nihal

    2015-04-01

    High numbers of proinflammatory cells (PMNLs), which are carried by the blood to ischemic tissue during reperfusion, are considered responsible for inducing the inflammatory response that occurs in ischemia-reperfusion (I/R) injury. Our objective was to determine the controlled reperfusion (CR) interval duration (CRID) that would minimize the injury caused by the PMNLs that infiltrate ischemic tissue. Animal groups were divided into the following groups: Sham group, ovarian I/R group (OIR), and ovarian ischemia controlled-reperfusion groups OICR-1, OICR-2, OICR-3, OICR-4, OICR-5, OICR-6, which had their ovarian artery opened and then closed for 10, 8, 6, 4, 2, or 1 s, respectively. The results show that the COX-2 activity and the gene expression decreased while the COX-1 activity and the gene expression were found to be increased in parallel to the shortening of the period in CRID. From the histopathological examinations, the findings of hemorrhage, edema, congested vascular structures, degenerated cells, and migration and adhesion of PMNLs were scaled as follows: Sham group < OICR-6 < OICR-5 < OICR-4 < OICR-3 < OICR-2 < OICR-1. The results from the histopathological assessments were consistent with the molecular and biochemical findings. In conclusion, our findings suggest that increased COX-2 activity plays a role in I/R injury of the rat ovary, and that controlled reperfusion for 3, 2, or 1 s following 2 h of ischemia may attenuate the effects of I/R injury. PMID:25730518

  13. Acute 7,12-dimethylbenz[a]anthracene exposure causes differential concentration-dependent follicle depletion and gene expression in neonatal rat ovaries

    PubMed Central

    Madden, Jill A.; Hoyer, Patricia B.; Devine, Patrick J.; Keating, Aileen F.

    2014-01-01

    Chronic exposure to the polycyclic aromatic hydrocarbon 7,12-dimethylbenz[a]anthracene (DMBA), generated during combustion of organic matter including cigarette smoke, depletes all ovarian follicle types in the mouse and rat, and in vitro models mimic this effect. To investigate the mechanisms involved in follicular depletion during acute DMBA exposure, two concentrations of DMBA at which follicle depletion has (75 nM) and has not (12.5 nM) been observed were investigated. Postnatal day four F344 rat ovaries were maintained in culture for four days before a single exposure to vehicle control (1% DMSO; CT) or DMBA (12 nM; low-concentration or 75 nM; high-concentration). After four or eight additional days of culture, DMBA-induced follicle depletion was evaluated via follicle enumeration. Relative to control, DMBA did not affect follicle numbers after 4 days of exposure, but induced large primary follicle loss at both concentrations after 8 days; while, the low-concentration DMBA also caused secondary follicle depletion. Neither concentration affected primordial or small primary follicle number. RNA was isolated and quantitative RT-PCR performed prior to follicle loss to measure mRNA levels of genes involved in xenobiotic metabolism (Cyp2e1, Gstmu, Gstpi, Ephx1), autophagy (Atg7, Becn1), oxidative stress response (Sod1, Sod2) and the phosphatidylinositol 3-kinase (PI3K) pathway (Kitlg, cKit, Akt1) 1, 2 and 4 days after exposure. With the exception of Atg7 and cKit, DMBA increased (P < 0.05) expression of all genes investigated. Also, BECN1 and pAKTThr308 protein levels were increased while cKIT was decreased by DMBA exposure. Taken together, these results suggest an increase in DMBA bioactivation, add to the mechanistic understanding of DMBA-induced ovotoxicity and raise concern regarding female low concentration DMBA exposures. PMID:24576726

  14. Morphometrical investigations on the reproductive activity of the ovaries in rats subjected to immobilization and to motion activity

    NASA Technical Reports Server (NTRS)

    Konstantinov, N.; Cheresharov, L.; Toshkova, S.

    1982-01-01

    Wistar-strain white female rats were divided into three groups, with the first group subjected to motion loading, the second used as control, and the third group was immobilized. A considerable reduction in numbers of corpora lutea was observed in the immobilized group, together with smaller numbers of embryos, high percent of embryo mortality, fetal growth retardation, and endometrium disorders. The control group showed no deviation from normal conditions, and there was slight improvement in reproductive activity of animals under motion loading.

  15. Time-of-flight secondary ion mass spectrometry imaging demonstrates the specific localization of deca-bromo-diphenyl-ether residues in the ovaries and adrenal glands of exposed rats.

    PubMed

    Seyer, Alexandre; Riu, Anne; Debrauwer, Laurent; Bourgès-Abella, Nathalie; Brunelle, Alain; Laprévote, Olivier; Zalko, Daniel

    2010-11-01

    Deca-bromo-diphenyl ether (DBDE) is one of the most efficient brominated flame retardant (BFR) available on the market. We recently demonstrated that when administered to female rat by oral route, DBDE is efficiently absorbed, with the highest residual concentrations found in two endocrine glands, namely the adrenal glands and the ovaries. Time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging, a technique usually used for the study of endogenous compounds, was applied for the first time to a persistent organic pollutant, allowing to detect and to precisely localize DBDE residues in these two target tissues. The detection of the bromide ion ((81)Br isotope) by TOF-SIMS mass spectrometry imaging allowed us to demonstrate a marked cortical tropism of DBDE residues for the adrenal glands in female rats dosed per os 2 mg·kg(-1) DBDE, daily, over 96 h. In ovaries, DBDE residues were found to be concentrated in spots corresponding to part of the corpora lutea. Hepatic residues of DBDE were found to be homogeneously distributed. Due to the intrinsic toxicity of DBDE, its accumulation in the adrenal glands and the ovaries may be connected to the mechanisms of actions by which DBDE could trigger endocrine disruption in mammals. PMID:20675151

  16. Polycystic Ovary Syndrome FAQ

    MedlinePlus

    f AQ FREQUENTLY ASKED QUESTIONS FAQ121 GYNECOLOGIC PROBLEMS Polycystic Ovary Syndrome (PCOS) • What are common signs and symptoms of polycystic ovary syndrome (PCOS)? • What causes PCOS? • What is insulin resistance? • ...

  17. Polycystic Ovary Syndrome

    MedlinePlus

    Polycystic ovary syndrome (PCOS) happens when a woman's ovaries or adrenal glands produce more male hormones than normal. One result is that cysts ( ... who are obese are more likely to have polycystic ovary syndrome. Symptoms of PCOS include: Infertility Pelvic pain Excess ...

  18. Glutathione S-transferase class mu regulation of apoptosis signal-related kinase 1 protein during VCD-induced ovotoxicity in neonatal rat ovaries

    PubMed Central

    Bhattacharya, Poulomi; Madden, Jill A.; Sen, Nivedita; Hoyer, Patricia B.; Keating, Aileen F.

    2013-01-01

    4-vinylcyclohexene diepoxide (VCD) destroys ovarian primordial and small primary follicles via apoptosis. In mice, VCD exposure induces ovarian mRNA expression of glutathione S-transferase (GST) family members, including isoform mu (Gstm). Extra-ovarian GSTM negatively regulates pro-apoptotic apoptosis signal-related kinase 1 (ASK1) through protein complex formation, which dissociates during stress, thereby initiating ASK1-induced apoptosis. The present study investigated the ovarian response of Gstm mRNA and protein to VCD. Induction of Ask1 mRNA at VCD-induced follicle loss onset was determined. Ovarian GSTM:ASK1 protein complex formation was investigated and VCD exposure effects thereon evaluated. Phosphatidylinositol-3 kinase (PI3K) regulation of GSTM protein was also studied. Postnatal day (PND) 4 rat ovaries were cultured in control media ±: 1) VCD (30 μM) for 2–8d; 2) VCD (30 μM) for 2d, followed by incubation in control media for 4d (acute VCD exposure); or 3) LY294002 (20 μM) for 6d. VCD exposure did not alter Gstm mRNA expression, however, GSTM protein increased (P < 0.05) after 6d of both the acute and chronic treatments. Ask1 mRNA increased (0.33-fold; P < 0.05) relative to control after 6d of VCD exposure. Ovarian GSTM:ASK1 protein complex formation was confirmed and, relative to control, the amount of GSTM bound to ASK1 increased 33% (P < 0.05) by chronic but with no effect of acute VCD exposure. PI3K inhibition increased (P < 0.05) GSTM protein by 40% and 71% on d4 and d6, respectively. These findings support involvement of GSTM in the ovarian response to VCD exposure, through regulation of pro-apoptotic ASK1. PMID:23274565

  19. Glutathione S-transferase class μ regulation of apoptosis signal-regulating kinase 1 protein during VCD-induced ovotoxicity in neonatal rat ovaries.

    PubMed

    Bhattacharya, Poulomi; Madden, Jill A; Sen, Nivedita; Hoyer, Patricia B; Keating, Aileen F

    2013-02-15

    4-Vinylcyclohexene diepoxide (VCD) destroys ovarian primordial and small primary follicles via apoptosis. In mice, VCD exposure induces ovarian mRNA expression of glutathione S-transferase (GST) family members, including isoform mu (Gstm). Extra-ovarian GSTM negatively regulates pro-apoptotic apoptosis signal-regulating kinase 1 (ASK1) through protein complex formation, which dissociates during stress, thereby initiating ASK1-induced apoptosis. The present study investigated the ovarian response of Gstm mRNA and protein to VCD. Induction of Ask1 mRNA at VCD-induced follicle loss onset was determined. Ovarian GSTM:ASK1 protein complex formation was investigated and VCD exposure effects thereon evaluated. Phosphatidylinositol-3 kinase (PI3K) regulation of GSTM protein was also studied. Postnatal day (PND) 4 rat ovaries were cultured in control media ± 1) VCD (30 μM) for 2-8 days; 2) VCD (30 μM) for 2 days, followed by incubation in control media for 4 days (acute VCD exposure); or 3) LY294002 (20 μM) for 6 days. VCD exposure did not alter Gstm mRNA expression, however, GSTM protein increased (P<0.05) after 6 days of both the acute and chronic treatments. Ask1 mRNA increased (0.33-fold; P<0.05) relative to control after 6 days of VCD exposure. Ovarian GSTM:ASK1 protein complex formation was confirmed and, relative to control, the amount of GSTM bound to ASK1 increased 33% (P<0.05) by chronic but with no effect of acute VCD exposure. PI3K inhibition increased (P<0.05) GSTM protein by 40% and 71% on d4 and d6, respectively. These findings support involvement of GSTM in the ovarian response to VCD exposure, through regulation of pro-apoptotic ASK1. PMID:23274565

  20. Acute 7,12-dimethylbenz[a]anthracene exposure causes differential concentration-dependent follicle depletion and gene expression in neonatal rat ovaries

    SciTech Connect

    Madden, Jill A.; Hoyer, Patricia B.; Devine, Patrick J.; Keating, Aileen F.

    2014-05-01

    Chronic exposure to the polycyclic aromatic hydrocarbon 7,12-dimethylbenz[a]anthracene (DMBA), generated during combustion of organic matter including cigarette smoke, depletes all ovarian follicle types in the mouse and rat, and in vitro models mimic this effect. To investigate the mechanisms involved in follicular depletion during acute DMBA exposure, two concentrations of DMBA at which follicle depletion has (75 nM) and has not (12.5 nM) been observed were investigated. Postnatal day four F344 rat ovaries were maintained in culture for four days before a single exposure to vehicle control (1% DMSO; CT) or DMBA (12 nM; low-concentration or 75 nM; high-concentration). After four or eight additional days of culture, DMBA-induced follicle depletion was evaluated via follicle enumeration. Relative to control, DMBA did not affect follicle numbers after 4 days of exposure, but induced large primary follicle loss at both concentrations after 8 days; while, the low-concentration DMBA also caused secondary follicle depletion. Neither concentration affected primordial or small primary follicle number. RNA was isolated and quantitative RT-PCR performed prior to follicle loss to measure mRNA levels of genes involved in xenobiotic metabolism (Cyp2e1, Gstmu, Gstpi, Ephx1), autophagy (Atg7, Becn1), oxidative stress response (Sod1, Sod2) and the phosphatidylinositol 3-kinase (PI3K) pathway (Kitlg, cKit, Akt1) 1, 2 and 4 days after exposure. With the exception of Atg7 and cKit, DMBA increased (P < 0.05) expression of all genes investigated. Also, BECN1 and pAKT{sup Thr308} protein levels were increased while cKIT was decreased by DMBA exposure. Taken together, these results suggest an increase in DMBA bioactivation, add to the mechanistic understanding of DMBA-induced ovotoxicity and raise concern regarding female low concentration DMBA exposures. - Highlights: • Acute DMBA exposures induce large primary and/or secondary follicle loss. • Acute DMBA exposure did not impact

  1. Serotonin transporter genotype x construction stress interaction in rats.

    PubMed

    Schipper, Pieter; Nonkes, Lourens J P; Karel, Peter; Kiliaan, Amanda J; Homberg, Judith R

    2011-09-30

    A well-known example for gene x environment interactions in psychiatry is the one involving the low activity (s) allelic variant of the serotonin transporter (5-HTT) promoter polymorphism (5-HTTLPR) that in the context of stress increases risk for depression. In analogy, 5-HTT knockout rodents are highly responsive to early life, but also adult external stressors, albeit conflicting data have been obtained. In our study on emotion and cognition using homozygous 5-HTT knockout (5-HTT(-/-)) and wild-type (5-HTT(+/+)) rats we have been confronted with animal facility construction, which were associated with severe lifetime stress (noise and vibrations). To assess the impact of construction stress on well-established 5-HTT(-/-) rat phenotypes we conducted ad hoc analyses of 5-HTT(-/-) and 5-HTT(+/+) rats that grew up before and during the construction. The reproductive capacity of the parents of the experimental 5-HTT(+/-) rats was significantly decreased. Further, 5-HTT(-/-) anxiety-related phenotypes in the elevated plus maze and social interaction tests were abolished after construction noise exposure, due to increased anxiety in 5-HTT(+/+) rats and decreased anxiety in 5-HTT(-/-) rats (social interaction test only). In addition, reversal learning was improved in 5-HTT(+/+) and, to a milder extent, decreased in 5-HTT(-/-) rats. Finally, construction stress genotype-independently increased behavioural despair in the forced swim test. In conclusion, severe construction stress induces 5-HTT genotype-dependent 'for-better-and-for-worse' effects. These data importantly contribute to the understanding of 5-HTT gene x environment interactions and show the risk of losing genotype effects by construction stress. PMID:21549766

  2. Interactions of amiodarone with digoxin in rats.

    PubMed Central

    Braunschweig, J.; Stäubli, M.; Studer, H.

    1987-01-01

    1. The influence of oral amiodarone treatment on the blood and tissue concentrations of digoxin was investigated in the anaesthetized rat by use of unlabelled and [3H]-digoxin. 2. Amiodarone diminished the total body clearance and the apparent volume of digoxin distribution by 60%. This reduction was due to a 50% reduction of the hepatobiliary clearance, whereas the renal clearance did not change. 3. Amiodarone treatment increased blood, myocardial and skeletal muscle [3H]-digoxin concentrations by 200% indicating passive equilibration between blood and these tissues, and resulting in unaltered tissue to blood ratios. In contrast, the liver concentration increased by 70% only and the liver to blood ratio therefore decreased under amiodarone treatment. 4. It is concluded that the hepatobiliary elimination of digoxin is decreased in amiodarone-treated rats compared to controls and is responsible for the increased levels of blood and tissue glycoside. PMID:3427268

  3. Absence of pharmacokinetic interaction between ofloxacin and fenbufen in rats.

    PubMed

    Katagiri, Y; Naora, K; Ichikawa, N; Hayashibara, M; Iwamoto, K

    1989-10-01

    The possible pharmacokinetic interaction between a new quinolone and fenbufen was investigated by comparing the plasma concentration-time profiles and serum protein binding of ofloxacin, fenbufen and its active metabolite, felbinac, in rats. The rats were administered intravenous doses of ofloxacin (5 mg kg-1), fenbufen (10 mg kg-1) alone or concomitantly. The plasma elimination half-lives were about 55 min in both groups. A slight elevation of plasma concentration of ofloxacin and a small decrease of its total body clearance were observed after its coadministration with fenbufen. The extent of ofloxacin binding to rat serum tended to be slightly reduced by fenbufen which coexisted at relatively high concentrations. Plasma concentration-time curves, pharmacokinetic parameters and serum protein binding of fenbufen and felbinac were not affected by the coadministration with ofloxacin. These results suggest that any substantive pharmacokinetic interaction may be unlikely after the concomitant administration of ofloxacin and fenbufen. PMID:2575153

  4. Glutathione S-transferase class mu regulation of apoptosis signal-regulating kinase 1 protein during VCD-induced ovotoxicity in neonatal rat ovaries

    SciTech Connect

    Bhattacharya, Poulomi; Madden, Jill A.; Sen, Nivedita; Hoyer, Patricia B.; Keating, Aileen F.

    2013-02-15

    4-Vinylcyclohexene diepoxide (VCD) destroys ovarian primordial and small primary follicles via apoptosis. In mice, VCD exposure induces ovarian mRNA expression of glutathione S-transferase (GST) family members, including isoform mu (Gstm). Extra-ovarian GSTM negatively regulates pro-apoptotic apoptosis signal-regulating kinase 1 (ASK1) through protein complex formation, which dissociates during stress, thereby initiating ASK1-induced apoptosis. The present study investigated the ovarian response of Gstm mRNA and protein to VCD. Induction of Ask1 mRNA at VCD-induced follicle loss onset was determined. Ovarian GSTM:ASK1 protein complex formation was investigated and VCD exposure effects thereon evaluated. Phosphatidylinositol-3 kinase (PI3K) regulation of GSTM protein was also studied. Postnatal day (PND) 4 rat ovaries were cultured in control media ± 1) VCD (30 μM) for 2–8 days; 2) VCD (30 μM) for 2 days, followed by incubation in control media for 4 days (acute VCD exposure); or 3) LY294002 (20 μM) for 6 days. VCD exposure did not alter Gstm mRNA expression, however, GSTM protein increased (P < 0.05) after 6 days of both the acute and chronic treatments. Ask1 mRNA increased (0.33-fold; P < 0.05) relative to control after 6 days of VCD exposure. Ovarian GSTM:ASK1 protein complex formation was confirmed and, relative to control, the amount of GSTM bound to ASK1 increased 33% (P < 0.05) by chronic but with no effect of acute VCD exposure. PI3K inhibition increased (P < 0.05) GSTM protein by 40% and 71% on d4 and d6, respectively. These findings support involvement of GSTM in the ovarian response to VCD exposure, through regulation of pro-apoptotic ASK1. - Highlights: ► GSTM protein increases in response to ovarian VCD exposure. ► VCD increases Ask1 mRNA at the onset of follicle loss. ► Ovarian GSTM binds more ASK1 protein during VCD-induced ovotoxicity. ► PI3K regulates ovarian GSTM protein.

  5. Rats' Novel Object Interaction as a Measure of Environmental Familiarity

    ERIC Educational Resources Information Center

    Wilkinson, Jamie L.; Herrman, Laura; Palmatier, Matthew I.; Bevins, Rick A.

    2006-01-01

    Environmental familiarization is a learning phenomenon embedded within most tasks used to study learning and motivation. Given its prevalence there is surprisingly little systematic behavioral research on factors affecting familiarization. The six experiments reported in the present report used rats' tendency to interact more with a novel object…

  6. Pharmacokinetic Interaction of Chrysin with Caffeine in Rats.

    PubMed

    Noh, Keumhan; Oh, Do Gyeong; Nepal, Mahesh Raj; Jeong, Ki Sun; Choi, Yongjoo; Kang, Mi Jeong; Kang, Wonku; Jeong, Hye Gwang; Jeong, Tae Cheon

    2016-07-01

    Pharmacokinetic interaction of chrysin, a flavone present in honey, propolis and herbs, with caffeine was investigated in male Sprague-Dawley rats. Because chrysin inhibited CYP1A-selective ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase activities in enriched rat liver microsomes, the pharmacokinetics of caffeine, a CYP 1A substrate, was studied following an intragastric administration with 100 mg/kg chrysin. In addition to the oral bioavailability of chrysin, its phase 2 metabolites, chrysin sulfate and chrysin glucuronide, were determined in rat plasma. As results, the pharmacokinetic parameters for caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) were not changed following chrysin treatment in vivo, despite of its inhibitory effect on CYP 1A in vitro. The bioavailability of chrysin was found to be almost zero, because chrysin was rapidly metabolized to its sulfate and glucuronide conjugates in rats. Taken together, it was concluded that the little interaction of chrysin with caffeine might be resulted from the rapid metabolism of chrysin to its phase 2 metabolites which would not have inhibitory effects on CYP enzymes responsible for caffeine metabolism. PMID:27098862

  7. Pharmacokinetic Interaction of Chrysin with Caffeine in Rats

    PubMed Central

    Noh, Keumhan; Oh, Do Gyeong; Nepal, Mahesh Raj; Jeong, Ki Sun; Choi, Yongjoo; Kang, Mi Jeong; Kang, Wonku; Jeong, Hye Gwang; Jeong, Tae Cheon

    2016-01-01

    Pharmacokinetic interaction of chrysin, a flavone present in honey, propolis and herbs, with caffeine was investigated in male Sprague-Dawley rats. Because chrysin inhibited CYP1A-selective ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase activities in enriched rat liver microsomes, the pharmacokinetics of caffeine, a CYP 1A substrate, was studied following an intragastric administration with 100 mg/kg chrysin. In addition to the oral bioavailability of chrysin, its phase 2 metabolites, chrysin sulfate and chrysin glucuronide, were determined in rat plasma. As results, the pharmacokinetic parameters for caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) were not changed following chrysin treatment in vivo, despite of its inhibitory effect on CYP 1A in vitro. The bioavailability of chrysin was found to be almost zero, because chrysin was rapidly metabolized to its sulfate and glucuronide conjugates in rats. Taken together, it was concluded that the little interaction of chrysin with caffeine might be resulted from the rapid metabolism of chrysin to its phase 2 metabolites which would not have inhibitory effects on CYP enzymes responsible for caffeine metabolism. PMID:27098862

  8. [Polycystic ovary syndrome].

    PubMed

    Vrbíková, Jana

    2015-10-01

    For diagnosing of polycystic ovary syndrome (PCOS) it is currently recommended to follow the ESHRE criteria. For diagnosis according to them two of the following three symptoms are sufficient: 1. morphology of polycystic ovaria, 2. clinical manifestations of hyperandrogenism or laboratory proof of hyperandrogenemia, and 3. oligo-anovulation. PCOS is a complex disorder in whose pathogenesis genetic and environmental effects interact. It is not a gynecological disorder alone, the syndrome is accompanied by insulin resistance which leads to increased incidence of type 2 diabetes mellitus and impaired glucose tolerance (4 times and twice, independently of BMI). Also gestational DM occurs more frequently. Dyslipidemia, arterial hypertension, elevated CRP and homocysteine levels, endothelial dysfunction and greater intima-media thickness are also more frequent. It is not quite clear, however, whether women with PCOS suffer cardiovascular events more frequently as well. More often than is accidental PCOS is associated with depression, anxiety and eating disorders, further with nonalcoholic steatohepatitis and with the sleep apnoea syndrome - especially in obese women. Therapeutic measures include non-pharmacological methods - lifestyle adjustments focused on weight reduction in obese individuals, cosmetic measures for dermatologic manifestation of hyperandrogenism, in particular laser and pharmacotherapy (combined hormonal contraceptives and antiandrogens). Menstrual irregularities can be treated with contraceptives or cyclical administration of gestagens, also metformin can be used. PMID:26486483

  9. Polycystic ovary disease

    MedlinePlus

    ... hormones. This may lead to changes in the menstrual cycle, cysts in the ovaries , trouble getting pregnant, and ... Symptoms Symptoms of PCOS include changes in the menstrual cycle, such as: Not getting a period after you ...

  10. A Dietary Medium-Chain Fatty Acid, Decanoic Acid, Inhibits Recruitment of Nur77 to the HSD3B2 Promoter In Vitro and Reverses Endocrine and Metabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome.

    PubMed

    Lee, Bao Hui; Indran, Inthrani Raja; Tan, Huey Min; Li, Yu; Zhang, Zhiwei; Li, Jun; Yong, Eu-Leong

    2016-01-01

    Hyperandrogenism is the central feature of polycystic ovary syndrome (PCOS). Due to the intricate relationship between hyperandrogenism and insulin resistance in PCOS, 50%-70% of these patients also present with hyperinsulinemia. Metformin, an insulin sensitizer, has been used to reduce insulin resistance and improve fertility in women with PCOS. In previous work, we have noted that a dietary medium-chain fatty acid, decanoic acid (DA), improves glucose tolerance and lipid profile in a mouse model of diabetes. Here, we report for the first time that DA, like metformin, inhibits androgen biosynthesis in NCI-H295R steroidogenic cells by regulating the enzyme 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase type 2 (HSD3B2). The inhibitory effect on HSD3B2 and androgen production required cAMP stimulation, suggesting a mechanistic action via the cAMP-stimulated pathway. Specifically, both DA and metformin reduced cAMP-enhanced recruitment of the orphan nuclear receptor Nur77 to the HSD3B2 promoter, coupled with decreased transcription and protein expression of HSD3B2. In a letrozole-induced PCOS rat model, treatment with DA or metformin reduced serum-free testosterone, lowered fasting insulin, and restored estrous cyclicity. In addition, DA treatment lowered serum total testosterone and decreased HSD3B2 protein expression in the adrenals and ovaries. We conclude that DA inhibits androgen biosynthesis via mechanisms resulting in the suppression of HSD3B2 expression, an effect consistently observed both in vitro and in vivo. The efficacy of DA in reversing the endocrine and metabolic abnormalities of the letrozole-induced PCOS rat model are promising, raising the possibility that diets including DA could be beneficial for the management of both hyperandrogenism and insulin resistance in PCOS. PMID:26465200

  11. Pattern of human chorionic gonadotropin binding in the polycystic ovary

    SciTech Connect

    Brawer, J.; Richard, M.; Farookhi, R. )

    1989-08-01

    The histologic evolution of polycystic ovaries in the estradiol valerate-treated rat coincides with the development of a unique plasma pattern of luteinizing hormone. To assess the role of luteinizing hormone in polycystic ovaries, it is necessary to evaluate the luteinizing hormone sensitivity of the specific tissues in the polycystic ovary. Therefore, we examined the pattern of luteinizing hormone binding sites in polycystic ovaries. Rats at 4 or 8 weeks after estradiol valerate treatment each received an intrajugular injection of iodine 125-labeled human chorionic gonadotropin. Some rats also received a 1000-fold excess of unlabeled human chorionic gonadotropin in the same injection. Ovaries were prepared for autoradiography. Dense accumulations of grains occurred over the theca of normal and atretic secondary follicles in all ovaries and over clusters of secondary interstitial cells. The iodine label was variable over the typically hypertrophied theca of precystic follicles. The theca of definitive cysts showed little or no label. These results indicate that cyst formation coincides with the loss of luteinizing hormone/human chorionic gonadotropin binding to the affected follicles.

  12. Immunohistochemistry of Paraffin Sections from Mouse Ovaries.

    PubMed

    Akkoyunlu, Gokhan; Tepekoy, Filiz

    2016-01-01

    Immunohistochemistry (IHC) is an efficient technique to detect cellular localizations of the proteins in paraffin-embedded tissues. It allows specific proteins to be visualized by the interaction of antibodies with an enzyme-substrate-chromogen system. Here, we describe indirect immunohistochemistry method for paraffin-embedded mouse ovaries fixed with Bouin's Fixative. PMID:27557588

  13. Human umbilical cord mesenchymal stem cell transplantation restores damaged ovaries

    PubMed Central

    Zhu, Shao-Fang; Hu, Hong-Bo; Xu, Hong-Yan; Fu, Xia-Fei; Peng, Dong-Xian; Su, Wei-Yan; He, Yuan-Li

    2015-01-01

    Ovarian injury because of chemotherapy can decrease the levels of sexual hormones and potentia generandi of patients, thereby greatly reducing quality of life. The goal of this study was to investigate which transplantation method for human umbilical cord mesenchymal stem cells (HUMSCs) can recover ovarian function that has been damaged by chemotherapy. A rat model of ovarian injury was established using an intraperitoneal injection of cyclophosphamide. Membrane-labelled HUMSCs were subsequently injected directly into ovary tissue or tail vein. The distribution of fluorescently labelled HUMSCs, estrous cycle, sexual hormone levels, and potentia generandi of treated and control rats were then examined. HUMSCs injected into the ovary only distributed to the ovary and uterus, while HUMSCs injected via tail vein were detected in the ovary, uterus, kidney, liver and lung. The estrous cycle, levels of sex hormones and potentia generandi of the treated rats were also recovered to a certain degree. Moreover, in some transplanted rats, fertility was restored and their offspring developed normally. While ovary injection could recover ovarian function faster, both methods produced similar results in the later stages of observation. Therefore, our results suggest that transplantation of HUMSCs by tail vein injection represents a minimally invasive and effective treatment method for ovarian injury. PMID:25922900

  14. Electro-acupuncture improves the social interaction behavior of rats.

    PubMed

    Zhang, Hong-Feng; Li, Han-Xia; Dai, Yu-Chuan; Xu, Xin-Jie; Han, Song-Ping; Zhang, Rong; Han, Ji-Sheng

    2015-11-01

    Oxytocin (OXT) and arginine-vasopressin (AVP) are two closely related neuropeptides and implicated in the regulation of mammalian social behaviors. A prior clinical study in our laboratory suggested that electro-acupuncture (EA) alleviated social impairment in autistic children accompanied by changes of peripheral levels of OXT and AVP. However, it remains unclear whether EA stimulation had an impact on central OXT and AVP levels. In the present study, rats were subjected to a single session of EA (sEA) or repeated sessions of EA (rEA). Following the stimulation, mRNA levels and peptide levels of OXT/AVP systems were determined. The results showed that sEA led to region-specific up-regulation of OXT and AVP mRNA levels in the hypothalamus where the peptides were produced, without affecting the content of OXT and AVP in the hypothalamus and peripheral blood. The rEA of 5 sessions in 9 days was given to the low socially interacting (LSI) rats. LSI rats that underwent rEA showed significant improvement of social behavior characterized by spending more time investigating the strange rats in the three-chamber sociability test. The improved sociability was accompanied by an up-regulation of mRNA and the peptide levels of OXT or AVP in SON of the hypothalamus as well as a significant increase of the serum level of AVP. It is concluded that activation of OXT/AVP systems may be associated with the pro-social effect caused by EA stimulation. PMID:26265492

  15. Interaction of dimethylbenzanthracene and diethylstilbestrol on mammary adenocarcinoma formation in female ACI rats

    SciTech Connect

    Shellabarger, C.J.; McKnight, B.; Stone, J.P.; Holtzman, S.

    1980-06-01

    It has been reported that x-irradiation and diethylstilbestrol (DES) act synergistically on mammary adenocarcinoma formation in female ACI rats. The physical carcinogen, x-irradiation, was replaced by a chemical carcinogen, dimethylbenzanthracene (DMBA), and their interaction was studied in this system. Thirty-three female ACI rats were given 13.3 mg of DMBA per 100 grams of body weight. A total of 10 mammary adenocarcinomas were found, 8 in rats with a single mammary adenocarcinoma and 2 in a single rat, over a 266-day study period. Twenty-nine rats were implanted with a cholesterol pellet containing 5 mg of DES, and a total of 47 mammary adenocarcinomas were found, 5 in rats with a single mammary adenocarcinoma and 42 in 5 rats with 2 or more mammary adenocarcinomas. Twenty-four rats were given a combined treatment of both compounds, DES 2 days before DMBA, and a total of 126 mammary adenocarcinomas were found, 2 in rats with a single mammary adenocarcinoma and 124 in 18 rats with 2 or more mammary adenocarcinomas. The interaction between DMBA and DES was interpreted to be synergistic in regard to the proportion of rats with one or more mammary adenocarcinomas, and the median times of appearance of both first and second mammary adenocarcinomas. These interactions between DMBA and DES resemble the previously reported synergistic interactions between radiation and DES on mammary adenocarcinoma formation in female ACI rats.

  16. Pharmacokinetic interaction between Kaempferia parviflora extract and sildenafil in rats.

    PubMed

    Mekjaruskul, Catheleeya; Sripanidkulchai, Bungorn

    2015-04-01

    Kaempferia parviflora (KP) is a plant widely used in Southeast Asia. Its major compounds are 3,5,7,3',4'-pentamethoxyflavone (PMF), 5,7,4'-trimethoxylflavone (TMF), and 5,7-dimethoxyflavone (DMF). This study investigated the effect of KP extract on the blood levels and pharmacokinetics of sildenafil co-administration in rats. Rats were randomly assigned to four groups. Groups 1, 2, and 3 were given sildenafil 20 mg/kg daily for 9 days. On days 4-9 of each treatment period, the treated rats received KP extract (250 mg/kg) and vehicle (groups 2 and 3, respectively). Group 4 received KP extract only (250 mg/kg daily for 9 days). Daily blood concentrations of sildenafil, PMF, TMF, and DMF were determined by HPLC to evaluate the daily blood level interactions. Additional blood samples were collected at various times on the last day of treatment to evaluate the pharmacokinetic interactions. The KP extract decreased blood levels of sildenafil on the first day of co-administration by 95 % but the percentage reduction was insignificant on subsequent days. When co-administered with KP extract, the area under the curve (AUC), maximum concentration (C max), and half-life (T 1/2) of sildenafil were decreased by 60-65, 40-52, and 32-54 %, respectively, with the elimination rate constant (K e) increased by 37-77 %. In addition, PMF, TMF, and DMF concentrations and their AUC, C max, T max, K e, and T 1/2 values were changed after co-administration of KP extract and sildenafil. PMID:25567192

  17. Human-animal interactions and animal welfare in conventionally and pen-housed rats.

    PubMed

    Augustsson, H; Lindberg, L; Höglund, A U; Dahlborn, K

    2002-07-01

    The main aim of the present study was to explore the significance of large group/greater pen housing (PH) versus standard Makrolon caging (ST) in three behaviour tests related to human-animal interactions in the adult male laboratory rat. The rats' perception of human interaction was tested in three behavioural tests, of which two reflected common practical procedures, capture and restraint, whereas the third was a human approach test in a Y-maze. The rats' anticipatory reactions to handling and the reactions to restraint did not differ between groups, but the ST rats approached a human hand more quickly than did the PH rats (P < 0.01). Although food intake did not differ, ST rats gained more weight (P < 0.01) and had higher total cholesterol values (P < 0.01) than PH rats. In conclusion, this study shows that housing rats in large groups in an enriched environment did not influence their anticipatory reaction to handling in normal handling situations. However, as the PH rats tended to have a longer approach latency than ST rats in the Y-maze there might be underlying differences in appraisal that are not detected in practical situations. In addition, the PH rats weighed less and had lower total cholesterol values than ST rats and their urine corticosterone values were higher. These effects are suggested to be due to higher physical activity in the PH rats, and the implications of this on the animal as a model is discussed. PMID:12144739

  18. Interactions between two propagating waves in rat visual cortex.

    PubMed

    Gao, X; Xu, W; Wang, Z; Takagaki, K; Li, B; Wu, J-Y

    2012-08-01

    Sensory-evoked propagating waves are frequently observed in sensory cortex. However, it is largely unknown how an evoked propagating wave affects the activity evoked by subsequent sensory inputs, or how two propagating waves interact when evoked by simultaneous sensory inputs. Using voltage-sensitive dye imaging, we investigated the interactions between two evoked waves in rat visual cortex, and the spatiotemporal patterns of depolarization in the neuronal population due to wave-to-wave interactions. We have found that visually-evoked propagating waves have a refractory period of about 300 ms, within which the response to a subsequent visual stimulus is suppressed. Simultaneous presentation of two visual stimuli at different locations can evoke two waves propagating toward each other, and these two waves fuse. Fusion significantly shortens the latency and half-width of the response, leading to changes in the spatial profile of evoked population activity. The visually-evoked propagating wave may also be suppressed by a preceding spontaneous wave. The refractory period following a propagating wave and the fusion between two waves may contribute to visual sensory processing by modifying the spatiotemporal profile of population neuronal activity evoked by sensory events. PMID:22561730

  19. Beaming into the rat world: enabling real-time interaction between rat and human each at their own scale.

    PubMed

    Normand, Jean-Marie; Sanchez-Vives, Maria V; Waechter, Christian; Giannopoulos, Elias; Grosswindhager, Bernhard; Spanlang, Bernhard; Guger, Christoph; Klinker, Gudrun; Srinivasan, Mandayam A; Slater, Mel

    2012-01-01

    Immersive virtual reality (IVR) typically generates the illusion in participants that they are in the displayed virtual scene where they can experience and interact in events as if they were really happening. Teleoperator (TO) systems place people at a remote physical destination embodied as a robotic device, and where typically participants have the sensation of being at the destination, with the ability to interact with entities there. In this paper, we show how to combine IVR and TO to allow a new class of application. The participant in the IVR is represented in the destination by a physical robot (TO) and simultaneously the remote place and entities within it are represented to the participant in the IVR. Hence, the IVR participant has a normal virtual reality experience, but where his or her actions and behaviour control the remote robot and can therefore have physical consequences. Here, we show how such a system can be deployed to allow a human and a rat to operate together, but the human interacting with the rat on a human scale, and the rat interacting with the human on the rat scale. The human is represented in a rat arena by a small robot that is slaved to the human's movements, whereas the tracked rat is represented to the human in the virtual reality by a humanoid avatar. We describe the system and also a study that was designed to test whether humans can successfully play a game with the rat. The results show that the system functioned well and that the humans were able to interact with the rat to fulfil the tasks of the game. This system opens up the possibility of new applications in the life sciences involving participant observation of and interaction with animals but at human scale. PMID:23118987

  20. Toxic effect of PBDE-47 on thyroid development, learning, and memory, and the interaction between PBDE-47 and PCB153 that enhances toxicity in rats.

    PubMed

    He, Ping; Wang, Aiguo; Niu, Qiang; Guo, Lijuan; Xia, Tao; Chen, Xuemin

    2011-04-01

    Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) are widespread environmental contaminants. There are potential interactive effects between PBDEs and PCBs, as these compounds share similar structures. The developmental neurotoxicity of 2, 2', 4, 4'-tetrabromodiphenyl ether (PBDE-47) and the interaction of PBDE-47 with 2, 2', 4, 4', 5, 5'-hexachlorobipheny (PCB153) were investigated herein, as the dominant congener forms of PBDEs and PCBs, respectively. SD rats were exposed to a single oral dose of PBDE-47 (1, 5, and 10 μg/g) and/or PCB153 (5 μg/g) on post-natal day (PND) 10. Concentrations of PBDE-47, triiodothyronine (T(3)), thyroxine (T(4)), and thyroid-stimulating hormone (TSH) in serum; organ-to-body weight ratios; as well as long-term learning and memory were measured in 2-month-old rats. The present study found that some doses of PBDE-47 decreased the organ-to-body weight ratios of the thyroid and uterus, decreased the concentration of T(4) in serum, and increased the organ-to-body weight ratio of the ovaries (p < 0.05). PCB153 could increase the action of PBDE-47 during combined exposure, but this interaction was not found between PBDE-47 and PCB153. In a Morris water maze experiment, the latency periods were significantly prolonged and time ratios were obviously depressed in all PBDE-47-treated groups compared to the control (p < 0.05); furthermore, significant interactions between PBDE-47 and PCB153 were observed (p < 0.05). In conclusion, PBDE-47 may depress thyroid development as well as the long-term learning and memory capabilities in adult rats exposed to PBDE-47 on PND 10. PCB153 can interact with PBDE-47, resulting in an increase in developmental neurotoxicity. PMID:20947653

  1. Circulating gonadotropins and ovarian adiponectin system are modulated by acupuncture independently of sex steroid or β-adrenergic action in a female hyperandrogenic rat model of polycystic ovary syndrome.

    PubMed

    Maliqueo, Manuel; Benrick, Anna; Alvi, Asif; Johansson, Julia; Sun, Miao; Labrie, Fernand; Ohlsson, Claes; Stener-Victorin, Elisabet

    2015-09-01

    Acupuncture with combined manual and low-frequency electrical stimulation, or electroacupuncture (EA), reduces endocrine and reproductive dysfunction in women with polycystic ovary syndrome (PCOS), likely by modulating sympathetic nerve activity or sex steroid synthesis. To test this hypothesis, we induced PCOS in rats by prepubertal implantation of continuous-release letrozole pellets (200 µg/day) or vehicle. Six weeks later, rats were treated for 5-6 weeks with low-frequency EA 5 days/week, subcutaneous injection of 17β-estradiol (2.0 µg) every fourth day, or a β-adrenergic blocker (propranolol hydrochloride, 0.1 mg/kg) 5 days/week. Letrozole controls were handled without needle insertion or injected with sesame oil every fourth day. Estrous cyclicity, ovarian morphology, sex steroids, gonadotropins, insulin-like growth factor I, bone mineral density, and gene and protein expression in ovarian tissue were measured. Low-frequency EA induced estrous-cycle changes, decreased high levels of circulating luteinizing hormone (LH) and the LH/follicle-stimulating hormone (FSH) ratio, decreased high ovarian gene expression of adiponectin receptor 2, and increased expression of adiponectin receptor 2 protein and phosphorylation of ERK1/2. EA also increased cortical bone mineral density. Propranolol decreased ovarian expression of Foxo3, Srd5a1, and Hif1a. Estradiol decreased circulating LH, induced estrous cycle changes, and decreased ovarian expression of Adipor1, Foxo3, and Pik3r1. Further, total bone mineral density was higher in the letrozole-estradiol group. Thus, EA modulates the circulating gonadotropin levels independently of sex steroids or β-adrenergic action and affects the expression of ovarian adiponectin system. PMID:25963796

  2. The Mammalian Ovary from Genesis to Revelation

    PubMed Central

    Edson, Mark A.; Nagaraja, Ankur K.; Matzuk, Martin M.

    2009-01-01

    Two major functions of the mammalian ovary are the production of germ cells (oocytes), which allow continuation of the species, and the generation of bioactive molecules, primarily steroids (mainly estrogens and progestins) and peptide growth factors, which are critical for ovarian function, regulation of the hypothalamic-pituitary-ovarian axis, and development of secondary sex characteristics. The female germline is created during embryogenesis when the precursors of primordial germ cells differentiate from somatic lineages of the embryo and take a unique route to reach the urogenital ridge. This undifferentiated gonad will differentiate along a female pathway, and the newly formed oocytes will proliferate and subsequently enter meiosis. At this point, the oocyte has two alternative fates: die, a common destiny of millions of oocytes, or be fertilized, a fate of at most approximately 100 oocytes, depending on the species. At every step from germline development and ovary formation to oogenesis and ovarian development and differentiation, there are coordinated interactions of hundreds of proteins and small RNAs. These studies have helped reproductive biologists to understand not only the normal functioning of the ovary but also the pathophysiology and genetics of diseases such as infertility and ovarian cancer. Over the last two decades, parallel progress has been made in the assisted reproductive technology clinic including better hormonal preparations, prenatal genetic testing, and optimal oocyte and embryo analysis and cryopreservation. Clearly, we have learned much about the mammalian ovary and manipulating its most important cargo, the oocyte, since the birth of Louise Brown over 30 yr ago. PMID:19776209

  3. Female Reproductive Aging Is Master-Planned at the Level of Ovary

    PubMed Central

    Banerjee, Sayani; Banerjee, Sutapa; Saraswat, Ghungroo; Bandyopadhyay, Soma Aditya; Kabir, Syed N.

    2014-01-01

    The ovary receives a finite pool of follicles during fetal life. Atresia remains the major form of follicular expenditure at all stages since development of ovary. The follicular reserve, however, declines at an exponential rate leading to accelerated rate of decay during the years preceding menopause. We examined if diminished follicle reserve that characterizes ovarian aging impacts the attrition rate. Premature ovarian aging was induced in rats by intra-embryonic injection of galactosyltransferase-antibody on embryonic day 10. On post-natal day 35 of the female litters, either a wedge of fat (sham control) or a wild type ovary collected from 25-day old control rats, was transplanted under the ovarian bursa in both sides. Follicular growth and atresia, and ovarian microenvironment were evaluated in the follicle-deficient host ovary and transplanted ovary by real time RT-PCR analysis of growth differentiation factor-9, bone morphogenetic protein 15, and kit ligand, biochemical evaluation of ovarian lipid peroxidation, superoxide dismutase (SOD) and catalase activity, and western blot analysis of ovarian pro- and anti-apoptotic factors including p53, bax, bcl2, and caspase 3. Results demonstrated that the rate of follicular atresia, which was highly preponderant in the follicle-deficient ovary of the sham-operated group, was significantly prevented in the presence of the transplanted ovary. As against the follicle-deficient ovary of the sham-operated group, the follicle-deficient host ovary as well as the transplanted ovary in the ovary-transplanted group exhibited stimulated follicle growth with increased expression of anti-apoptotic factors and down regulation of pro-apoptotic factors. Both the host and transplanted ovaries also had significantly lower rate of lipid peroxidation with increased SOD and catalase activity. We conclude that the declining follicular reserve is perhaps the immediate thrust that increases the rate of follicle depletion during the final

  4. Differences in social interaction- vs. cocaine reward in mouse vs. rat.

    PubMed

    Kummer, Kai K; Hofhansel, Lena; Barwitz, Constanze M; Schardl, Aurelia; Prast, Janine M; Salti, Ahmad; El Rawas, Rana; Zernig, Gerald

    2014-01-01

    We previously developed rat experimental models based on the conditioned place preference (CPP) paradigm in which only four 15-min episodes of dyadic social interaction with a sex- and weight-matched male Sprague Dawley (SD) rat (1) reversed CPP from cocaine to social interaction despite continuing cocaine training, and (2) prevented the reacquisition/re-expression of cocaine CPP. In a concurrent conditioning schedule, pairing one compartment with social interaction and the other compartment with 15 mg/kg cocaine injections, rats spent the same amount of time in both compartments and the most rewarding sensory component of the composite stimulus social interaction was touch (taction). In the present study, we validated our experimental paradigm in C57BL/6 mice to investigate if our experimental paradigm may be useful for the considerable number of genetically modified mouse models. Only 71% of the tested mice developed place preference for social interaction, whereas 85% of the rats did. Accordingly, 29% of the mice developed conditioned place aversion (CPA) to social interaction, whereas this was true for only 15% of the rats. In support of the lesser likelihood of mice to develop a preference for social interaction, the average amount of time spent in direct contact was 17% for mice vs. 79% for rats. In animals that were concurrently conditioned for social interaction vs. cocaine, the relative reward strength for cocaine was 300-fold higher in mice than in rats. Considering that human addicts regularly prefer drugs of abuse to drug-free social interaction, the present findings suggest that our experimental paradigm of concurrent CPP for cocaine vs. social interaction is of even greater translational power if performed in C57BL/6 mice, the genetic background for most transgenic rodent models, than in rats. PMID:25368560

  5. Interaction of human lactoferrin with the rat liver

    SciTech Connect

    Debanne, M.T.; Regoeczi, E.; Sweeney, G.D.; Krestynski, F.

    1985-04-01

    Binding of human lactoferrin (hLf) by purified rat liver plasma membranes was studied to clarify whether the liver possesses specific hLf receptors. The binding was rapid between 4 degrees and 37 degrees C, with a pH optimum close to 5.0. At 22 degrees C and in glycine-NaOH (5 mM, pH 7.4) containing 150 mM NaCl and 0.5% albumin, 1 microgram of membrane bound a maximum of 11.8 ng hLf. The dissociation constant of the interaction was 1.6 X 10(-7) M. Other proteins of high isoelectric points (lactoperoxidase, lysozyme, and particularly salmine sulfate) and a piperazine derivative inhibited hLf binding in a concentration- dependent manner. In contrast, monosaccharides (galactose, N- acetylgalactosamine, mannose, and fucose) were ineffective. By omitting NaCl from the incubation buffer, binding was increased 3.6-fold. Erythrocyte ghosts bound hLf less firmly and alveolar macrophages more firmly than hepatic plasma membranes. Liver cell fractionations performed after the intravenous injection of labeled hLf showed that approximately 88% of the hepatic radioligand was associated with parenchymal cells. When binding was expressed per unit of cell volume, however, more hLf was present in nonparenchymal than in parenchymal cells, implying that the above value was determined by the relative cell masses rather than affinities alone. It is concluded that the binding of hLf by hepatic plasma membranes is electrostatic, i.e., is mediated by the cationic nature of the ligand, and that it is explicable in terms of a ''specific nonreceptor interaction'' of the generalized type proposed by Cuatrecasas and Hollenberg.

  6. Polycystic ovary syndrome.

    PubMed

    Azziz, Ricardo; Carmina, Enrico; Chen, ZiJiang; Dunaif, Andrea; Laven, Joop S E; Legro, Richard S; Lizneva, Daria; Natterson-Horowtiz, Barbara; Teede, Helena J; Yildiz, Bulent O

    2016-01-01

    Polycystic ovary syndrome (PCOS) affects 5-20% of women of reproductive age worldwide. The condition is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology (PCOM) - with excessive androgen production by the ovaries being a key feature of PCOS. Metabolic dysfunction characterized by insulin resistance and compensatory hyperinsulinaemia is evident in the vast majority of affected individuals. PCOS increases the risk for type 2 diabetes mellitus, gestational diabetes and other pregnancy-related complications, venous thromboembolism, cerebrovascular and cardiovascular events and endometrial cancer. PCOS is a diagnosis of exclusion, based primarily on the presence of hyperandrogenism, ovulatory dysfunction and PCOM. Treatment should be tailored to the complaints and needs of the patient and involves targeting metabolic abnormalities through lifestyle changes, medication and potentially surgery for the prevention and management of excess weight, androgen suppression and/or blockade, endometrial protection, reproductive therapy and the detection and treatment of psychological features. This Primer summarizes the current state of knowledge regarding the epidemiology, mechanisms and pathophysiology, diagnosis, screening and prevention, management and future investigational directions of the disorder. PMID:27510637

  7. Soy but not Bisphenol A (BPA) Induces Hallmarks of Polycystic Ovary Syndrome (PCOS) and Related Metabolic co-Morbidities in Rats

    PubMed Central

    Patisaul, Heather B.; Mabrey, Natalie; Adewale, Heather B.; Sullivan, Alana W.

    2014-01-01

    Polycystic ovarian syndrome (PCOS) is the most common female endocrine disorder with a prevalence as high as 8–15% depending on ethnicity and the diagnostic criteria employed. The basic pathophysiology and mode of inheritance remain unclear, but environmental factors such as diet, stress and chemical exposures are thought to be contributory. Developmental exposure to endocrine disrupting compounds (EDCs) have been hypothesized to exacerbate risk, in part because PCOS hallmarks and associated metabolic co-morbidities can be reliably induced in animal models by perinatal androgen exposure. Here we show that lifetime exposure to a soy diet, containing endocrine active phytoestrogens, but not developmental exposure (gestational day 6 – lactational day 40) to the endocrine disrupting monomer Bisphenol A (BPA), can induce key features of PCOS in the rat; results which support the hypothesis that hormonally active diets may contribute to risk when consumed throughout gestation and post-natal life. PMID:25242113

  8. Irbesartan, an angiotensin II receptor antagonist, with selective PPAR-gamma-modulating activity improves function and structure of chemotherapy-damaged ovaries in rats.

    PubMed

    Abdel-Raheem, Ihab T; Omran, Gamal A; Katary, Mohamed Alaa

    2015-06-01

    Cyclophosphamide (CYP) is a chemotherapeutic agent with a potent ovarian toxic effect. CYP induces granulosa cell apoptosis and oxidative stress. Irbesartan (IRB) is a unique ARB with a peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonistic activity. As PPAR-ɣ activation exerts anti-inflammatory effects and reduces ROS production, IRB may further reduce inflammatory chemokine expression and suppress apoptotic cell death. Therefore, this study aimed to evaluate the effects of IRB on the development of CYP-induced ovarian damage. Rats were divided into four groups: control group, IRB group (100 mg/kg, orally), CYP group (100 mg/kg, i.p. single injection), and IRB+CYP group (IRB administered 9 days before and 6 days after CYP administration). Rats sacrificed on day 16 of experiment; estradiol (E2), FSH, and TNF-α levels were estimated in serum. Reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) and caspase-3 activities, myeloperoxidase (MPO), and IL-10 levels were determined in ovarian tissues. Protein expressions of p53, caspase-3, Ki-67, and Rad-51 were estimated by immunohistochemical and Western blot techniques. CYP produced ovarian damage as indicated from the decline in serum E2; elevation in FSH; unbalance in tissue oxidative stress parameters; increase in MPO, TNF-α levels, caspase-3 activity/expression, p53, and Rad-51 expression; and decrease in IL-10 contents, without effect on Ki-67. On the other hand, IRB, significantly reduced the toxic effects of CYP as indicted from normalization of E2, FSH, oxidative stress, apoptotic, and inflammatory mediators. These data were further supported by histopathological studies. Thus, co-administration of IRB may be promising in alleviating the ovarian toxic effects of CYP. PMID:25824615

  9. High affinity binding of [3H]propionyl-[Met(O2)11]substance P(7-11), a tritiated septide-like peptide, in Chinese hamster ovary cells expressing human neurokinin-1 receptors and in rat submandibular glands.

    PubMed

    Sagan, S; Beaujouan, J C; Torrens, Y; Saffroy, M; Chassaing, G; Glowinski, J; Lavielle, S

    1997-07-01

    Propionyl-[Met(O2)11]substance P(7-11) [ALIE-124 or propionyl-[Met(O2)11]SP(7-11)] has been designed as a septide-like ligand adequate for tritiation and, therefore, adequate for binding studies. In Chinese hamster ovary (CHO) cells expressing human tachykinin neurokinin (NK)-1 receptors, ALIE-124 displaced [3H][Pro9]substance P (SP) from its binding site at micromolar concentrations. However, ALIE-124 stimulated phosphatidylinositol hydrolysis, as previously shown for septide-like peptides. With [3H]ALIE-124 (95 Ci/mmol), we have been able to reveal a high affinity binding site in CHO cells (Kd = 6.6 +/- 1.0 nM), with a low maximal binding capacity. [3H]ALIE-124 specific maximal binding represented only 15-20% of that observed with [3H][Pro9]SP in CHO cells. Septide-like peptides, including septide and NKA, were potent competitors (in the nanomolar range) of [3H]ALIE-124 specific binding site. Interestingly, SP and [Pro9]SP were also potent competitors, with 10-fold greater potency for sites labeled with [3H]ALIE-124 than for sites labeled with [3H][Pro9]SP. The NK-1 antagonist RP 67580 also showed a higher potency for [3H]ALIE-124 than for [3H][Pro9]SP-specific binding sites. NKB and [Lys5,methyl-Leu9,Nle10]NKA(4-10) displaced [3H]ALIE-124 binding but with lower potency, whereas senktide had no affinity. The existence of [3H]ALIE-124 specific binding sites was also demonstrated in rat submandibular gland. In this tissue, [3H]ALIE-124 specific maximal binding was higher, reaching 40-50% of that achieved with [3H][Pro9]SP. PMID:9224821

  10. Effects of psychostimulants on social interaction in adult male rats.

    PubMed

    Šlamberová, Romana; Mikulecká, Anna; Macúchová, Eva; Hrebíčková, Ivana; Ševčíková, Mária; Nohejlová, Kateryna; Pometlová, Marie

    2015-12-01

    Psychostimulants are known to have a huge impact on different forms of social behaviour. The aim of the present study was to compare the effects of three different psychostimulants [amphetamine, cocaine and 3,4 methylenedimethoxyamphetamine (MDMA)] on social interaction (SI) in adult male rats. The SI test was performed in a familiar arena and under low-stress environmental conditions. Experimental animals received amphetamine (0.5, 1.0, 1.5 mg/kg), cocaine (0.5, 1.0, 1.5, 2.5, 5.0, 10.0 mg/kg) or MDMA (2.5, 5.0, 10 mg/kg) and control animals received saline (1 ml/kg) 45 min before the SI test. Time spent in SI (individual patterns of social behaviour) and nonsocial activities (locomotion and rearing) were video recorded and then analysed offline, with the following results: (a) all doses of amphetamine decreased SI. Specifically, all doses of amphetamine decreased mutual sniffing, and the higher doses also decreased allo-grooming and following behaviours. (b) The higher doses of cocaine decreased SI, especially mutual sniffing, allo-grooming and climbing over. Cocaine at the dose of 5.0 mg/kg increased genital investigation compared with lower doses. (c) All doses of MDMA decreased mutual sniffing and climbing over; the two higher doses decreased allo-grooming behaviour, and only the highest dose decreased following. The two higher doses of amphetamine and all the doses of MDMA increased locomotion and rearing; cocaine did not affect locomotion, but increased rearing at higher doses. In conclusion, the results confirm the well-known finding that psychostimulants suppress SI, but also show novel differences in the effects of psychostimulants on specific patterns of SI. PMID:26061354

  11. Interaction of maternal separation on the UCh rat cerebellum.

    PubMed

    Oliveira, S A; Fontanelli, B A F; Stefanini, M A; Chuffa, L G A; Teixeira, G R; Lizarte, F S N; Tirapelli, L F; Quitete, V H A; Matheus, S M M; Padovani, C R; Martinez, M; Martinez, F E

    2014-01-01

    Maternal care is the main source of signals and stimuli for proper development, growth, and production of adjustment responses to stressful factors. Adverse experiences in childhood are associated with a vulnerability to developing abusive ethanol ingestion via alterations of the response of the hypothalamic-pituitary-adrenal axis. Alcoholism causes global brain abnormalities, with the cerebellum being one of the most susceptible areas. We evaluated the effect of maternal separation on the cerebellum structure of male UCh rats. Adult male UChA (low 10% ethanol consumption) and UChB (high 10% ethanol consumption) rats were divided in to four experimental groups: (1) UChA, (2) UChA maternal separation (MS), (3) UChB, and (4) UChB MS. The MS occurred between the 4th and 14th days of age, for 240 min day(-1) . Euthanasia was performed at 120 days of age. An image analysis system was used to measure cerebellar cortical height and Purkinje cellular area and height in five rats from each group. The cerebellar sections were stained with antibodies against IGFR-I. MS did not alter the ethanol consumption of UChA and UChB rats. Corticosterone level was significantly higher in UChA MS and UChB MS rats than in UChA and UChB rats. The Purkinje cellular area and height were higher in UChA MS rats. IGFR-I expression was observed in the cortical glomerular area of UChA MS and UChB MS rats. MS altered the Purkinje cells in the cerebella of male UCh rats. PMID:24203397

  12. Carcinoma of the Ovary

    PubMed Central

    Weekes, Leroy R.; Watkins, Sue A.

    1981-01-01

    The data for this paper are based on 50 patients discharged from the Queen of Angels Hospital with a diagnosis of carcinoma of the ovary from 1972 to 1978. Currently, ovarian cancer is the leading cause of death of all pelvic malignancies. Peak incidence of ovarian cancer is found in women between 40 to 65 years of age. Symptomatology includes often vague abdominal discomfort, dyspepsia, and other digestive disorders which may be present for several months prior to diagnosis. The workup for suspected ovarian cancer should include a careful history, physical examination, pelvic, and rectal examinations, Pap smear, CBC, urinalysis, SMA 12 (blood chemistries), chest x-ray, and intravenous pyelography as indicated. Sonography, lymphangiography are optional. Traditionally, operative treatment has been the keystone of management for ovarian carcinoma. In view of the unsatisfactory results with operation and radiotherapy in disseminated disease, chemotherapy has been used widely. Hope for the future lies in further development of immunodiagnosis and immunotherapy. PMID:7310921

  13. Relationship between inhibition of cyclic AMP production in Chinese hamster ovary cells expressing the rat D2(444) receptor and antagonist/agonist binding ratios.

    PubMed Central

    Harley, E. A.; Middlemiss, D. N.; Ragan, C. I.

    1995-01-01

    1. Radioligand binding assays using [3H]-(-)-sulpiride, in the presence of 1 mM ethylenediaminetetraacetic acid (EDTA) and 100 microM guanylylimidodiphosphate (GppNHp) and [3H]-N0437 were developed to label the low and high agonist affinity states of the rD2(444) receptor (long form of the rat D2 receptor) respectively. The ratios of the affinities of compounds in these two assays (Kapp [3H]-(-)-supiride/Kapp [3H]-N-0437) were then calculated. 2. The prediction that the binding ratio reflected the functional efficacy of a compound was supported by measurement of the ability of a number of compounds acting at dopamine receptors to inhibit rD2(444)-mediated inhibition of cyclic AMP production. When the rank order of the ratios of a number of these compounds was compared to their ability to inhibit the production of cyclic AMP, a significant correlation was seen (Spearman rank correlation coefficient = 0.943, P = 0.01). 3. In conclusion, the sulpiride/N-0437 binding ratio reliably predicted the efficacy of compounds acting at dopamine receptors to inhibit cyclic AMP production mediated by the rD2(444) receptor. PMID:7582561

  14. Accentuated Decrease in Social Interaction in Rats Subjected to Repeated Ethanol Withdrawals

    PubMed Central

    Overstreet, David H.; Knapp, Darin J.; Breese, George R.

    2010-01-01

    Background Previous work has shown that repeated withdrawals from chronic ethanol exposure can kindle seizures in rodents. In this article, the effects of a three-cycle model of ethanol exposure and withdrawal on the social interaction test of anxiety are summarized. Methods Rats were exposed to ethanol (7% or 4.5%) diets over three periods of 5 days, with 2 days of withdrawal between cycles. Between 5 and 6 hr after the ethanol was removed, pairs of rats were placed in open field chambers for the assessment of social interaction behavior and locomotor activity. Results After the third cycle of ethanol (7%) presentation, both male and female rats exhibited lower social interaction behavior (more anxiety) and activity than after a single cycle. Rats exposed to a similar amount of ethanol but tested while ethanol was still available did not exhibit a reduction in social interaction. The decrease in social interaction was still present for up to 24 hr but had disappeared by 48 hr after ethanol was withdrawn. When rats were allowed 8 or 16 days to recover from the effects of the three-cycle protocol, a further exposure to 5 days of 7% ethanol diet resulted in a reduction in social interaction on withdrawal similar to that seen from the three-cycle protocol. In contrast, rats exposed continuously to 7% ethanol diet for 15 consecutive days exhibited higher levels of social interaction when maintained on control diet for 8 or 16 days and then reexposed to ethanol. Rats that were exposed to the three-cycle protocol and allowed 32 days to recover before being reexposed to ethanol still had a partial deficit in social interaction. Finally, animals subjected to repeated withdrawals from 4.5% ethanol exhibited a reduction in social interaction without a change in activity after the final withdrawal from ethanol, whereas rats exposed continuously to a 4.5% ethanol diet did not exhibit a reduction in social interaction or activity. Neither blood ethanol concentrations nor

  15. Brown adipose tissue transplantation ameliorates polycystic ovary syndrome.

    PubMed

    Yuan, Xiaoxue; Hu, Tao; Zhao, Han; Huang, Yuanyuan; Ye, Rongcai; Lin, Jun; Zhang, Chuanhai; Zhang, Hanlin; Wei, Gang; Zhou, Huiqiao; Dong, Meng; Zhao, Jun; Wang, Haibin; Liu, Qingsong; Lee, Hyuek Jong; Jin, Wanzhu; Chen, Zi-Jiang

    2016-03-01

    Polycystic ovary syndrome (PCOS), which is characterized by anovulation, hyperandrogenism, and polycystic ovaries, is a complex endocrinopathy. Because the cause of PCOS at the molecular level is largely unknown, there is no cure or specific treatment for PCOS. Here, we show that transplantation of brown adipose tissue (BAT) reversed anovulation, hyperandrogenism, and polycystic ovaries in a dehydroepiandrosterone (DHEA)-induced PCOS rat. BAT transplantation into a PCOS rat significantly stabilized menstrual irregularity and improved systemic insulin sensitivity up to a normal level, which was not shown in a sham-operated or muscle-transplanted PCOS rat. Moreover, BAT transplantation, not sham operation or muscle transplantation, surprisingly improved fertility in PCOS rats. Interestingly, BAT transplantation activated endogenous BAT and thereby increased the circulating level of adiponectin, which plays a prominent role in whole-body energy metabolism and ovarian physiology. Consistent with BAT transplantation, administration of adiponectin protein dramatically rescued DHEA-induced PCOS phenotypes. These results highlight that endogenous BAT activity is closely related to the development of PCOS phenotypes and that BAT activation might be a promising therapeutic option for the treatment of PCOS. PMID:26903641

  16. Brown adipose tissue transplantation ameliorates polycystic ovary syndrome

    PubMed Central

    Yuan, Xiaoxue; Hu, Tao; Zhao, Han; Huang, Yuanyuan; Ye, Rongcai; Lin, Jun; Zhang, Chuanhai; Zhang, Hanlin; Wei, Gang; Zhou, Huiqiao; Dong, Meng; Zhao, Jun; Wang, Haibin; Liu, Qingsong; Lee, Hyuek Jong; Jin, Wanzhu; Chen, Zi-Jiang

    2016-01-01

    Polycystic ovary syndrome (PCOS), which is characterized by anovulation, hyperandrogenism, and polycystic ovaries, is a complex endocrinopathy. Because the cause of PCOS at the molecular level is largely unknown, there is no cure or specific treatment for PCOS. Here, we show that transplantation of brown adipose tissue (BAT) reversed anovulation, hyperandrogenism, and polycystic ovaries in a dehydroepiandrosterone (DHEA)-induced PCOS rat. BAT transplantation into a PCOS rat significantly stabilized menstrual irregularity and improved systemic insulin sensitivity up to a normal level, which was not shown in a sham-operated or muscle-transplanted PCOS rat. Moreover, BAT transplantation, not sham operation or muscle transplantation, surprisingly improved fertility in PCOS rats. Interestingly, BAT transplantation activated endogenous BAT and thereby increased the circulating level of adiponectin, which plays a prominent role in whole-body energy metabolism and ovarian physiology. Consistent with BAT transplantation, administration of adiponectin protein dramatically rescued DHEA-induced PCOS phenotypes. These results highlight that endogenous BAT activity is closely related to the development of PCOS phenotypes and that BAT activation might be a promising therapeutic option for the treatment of PCOS. PMID:26903641

  17. Cannabidiol reverses the reduction in social interaction produced by low dose Delta(9)-tetrahydrocannabinol in rats.

    PubMed

    Malone, Daniel Thomas; Jongejan, Dennis; Taylor, David Alan

    2009-08-01

    While Delta(9)-tetrahydrocannabinol (THC) is the main psychoactive constituent of the cannabis plant, a non-psychoactive constituent is cannabidiol (CBD). CBD has been implicated as a potential treatment of a number of disorders including schizophrenia and epilepsy and has been included with THC in a 1:1 combination for the treatment of conditions such as neuropathic pain. This study investigated the effect of THC and CBD, alone or in combination, on some objective behaviours of rats in the open field. Pairs of rats were injected with CBD or vehicle followed by THC or vehicle and behaviour in the open field was assessed for 10 min. In vehicle pretreated rats THC (1 mg/kg) significantly reduced social interaction between rat pairs. Treatment with CBD had no significant effect alone, but pretreatment with CBD (20 mg/kg) reversed the THC-induced decreases in social interaction. A higher dose of THC (10 mg/kg) produced no significant effect on social interaction. However, the combination of high dose CBD and high dose THC significantly reduced social interaction between rat pairs, as well as producing a significant decrease in locomotor activity. This data suggests that CBD can reverse social withdrawal induced by low dose THC, but the combination of high dose THC and CBD impairs social interaction, possibly by decreasing locomotor activity. PMID:19393686

  18. Conditioned place preference for social interaction in rats: contribution of sensory components

    PubMed Central

    Kummer, Kai; Klement, Sabine; Eggart, Vincent; Mayr, Michael J.; Saria, Alois; Zernig, Gerald

    2011-01-01

    A main challenge in the therapy of drug dependent individuals is to help them reactivate interest in non-drug-associated activities. We previously developed a rat experimental model based on the conditioned place preference (CPP) paradigm in which only four 15-min episodes of social interaction with a gender- and weight-matched male Sprague Dawley rat (1) reversed CPP from cocaine to social interaction despite continuing cocaine training and (2) prevented the reinstatement of cocaine CPP. In the present study, we investigated which of the sensory modalities of the composite stimulus “social interaction” contributes most to the rats' preference for it. If touch was limited by steel bars spaced at a distance of 2 cm and running across the whole length of a partitioning, CPP was still acquired, albeit to a lesser degree. If both rats were placed on the same side of a partitioning, rats did not develop CPP for social interaction. Thus, decreasing the available area for social interaction from 750 to 375 cm2 prevented the acquisition of CPP to social interaction despite the fact that animals could touch each other more intensely than through the bars of the partitioning. When touch was fully restricted by a glass screen dividing the conditioning chambers, and the only sensory modalities left were visual and olfactory cues, place preference shifted to place aversion. Overall, our findings indicate that the major rewarding sensory component of the composite stimulus “social interaction” is touch (taction). PMID:22232578

  19. Tumours of the ovary

    PubMed Central

    Nielsen, Svend W.; Misdorp, W.; McEntee, Kenneth

    1976-01-01

    Ovarian tumours are common in animals, the majority occurring in bitches and cows. The two most important germ cell tumours were dysgerminoma and teratoma; these morphologically resemble their counterparts in women, with the exception that teratomas in animals tend less to malignancy. The granulosa cell tumour is the most frequent sex cord-stromal tumour in all six species and it may contain luteinized areas or show differentiation towards a Sertoli cell pattern. The canine papillary adenoma and papillary adenocarcinoma, which are as common as granulosa tumours, have several features in common with their counterparts in women: they are of similar histological appearance, are frequently bilateral, and the adenocarcinomas have a great propensity for peritoneal implantation metastasis. Ovarian cysts are frequent in the bitch, sow, and cow and may originate from five different anatomical structures in the ovary. ImagesFig. 1Fig. 2 and 3Fig. 20-22Fig. 8-10Fig. 15 and 16Fig. 23Fig. 24Fig. 25Fig. 26Fig. 17-19Fig. 4 and 5Fig. 6 and 7Fig. 11Fig. 12Fig. 13 and 14 PMID:1086151

  20. Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats.

    PubMed

    Salti, Ahmad; Kummer, Kai K; Sadangi, Chinmaya; Dechant, Georg; Saria, Alois; El Rawas, Rana

    2015-12-01

    We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens. PMID:26300300

  1. Assessment of pharmacokinetic interaction of spirulina with glitazone in a type 2 diabetes rat model.

    PubMed

    Gupta, Annu; Nair, Anroop; Kumria, Rachna; Al-Dhubiab, Bandar-E; Chattopadhyaya, Ipshita; Gupta, Sumeet

    2013-12-01

    The objective of the current study was to assess the possible pharmacokinetic interactions of spirulina with glitazones in an insulin resistance rat model. Wistar male albino rats were equally divided into five groups: insulin resistant rats+spirulina (500 mg/kg)+pioglitazone (10 mg/kg), insulin resistant rats+pioglitazone (10 mg/kg), insulin resistant rats+spirulina (500 mg/kg)+rosiglitazone (10 mg/kg), insulin resistant rats+rosiglitazone (10 mg/kg), and insulin resistant rats+spirulina (500 mg/kg). Described doses of pioglitazone, rosiglitazone, or spirulina were per orally administered and the plasma drug concentrations were determined. The pharmacokinetic parameters such as Tmax, Cmax, AUC(0-α), t1/2, and Kel were determined by plotting the drug concentration as a function of time. The data observed in this acute study indicated that there was no statistically significant difference in any of the pharmacokinetic parameters (Tmax, Cmax, AUC(0-α), t1/2, and Kel) of glitazones (pioglitazone, rosiglitazone) or spirulina, when they were coadministered. Given the promising results, this study concludes that the coadministration of spirulina does not influence the pharmacokinetics of glitazones in a type 2 diabetes rat model. Further chronic in vivo studies are recommended to assess the real time effect. PMID:24328701

  2. Trimethyltin-induced neuropathy in the rat: interaction with thermoregulation.

    PubMed

    Gordon, C J; O'Callaghan, J P

    1995-01-01

    The enhanced production of glial fibrillary acidic protein (GFAP) by astroglia appears to be a general response of the CNS to many types of toxic insult. The organometallic neurotoxicant, trimethyltin (TMT), is one such agent known to increase the production of GFAP as a consequence of widespread neuronal destruction. TMT also leads to transient reductions in body temperature (Tb), a response which may alter the neurotoxic effects of this compound. To study the role of Tb in the neurotoxic effects of TMT, rats were injected (i.v.) with saline or 8.0 mg/kg TMT and maintained at ambient temperatures (Ta) of 16, 22, or 30 degrees C for 72 hr while Tb (core) was measured periodically. Animals were then housed at a Ta of 22 degrees C for 35 days after which time their brains were removed and dissected into hippocampus, cerebral cortex, striatum, midbrain and cerebellum for subsequent analysis of GFAP. TMT led to a significant decrease in Tb of rats housed at 22 degrees C measured 3 hr after treatment. Tb of rats maintained at Ta's of 16 and 30 degrees C was unaffected by TMT initially (i.e., no hypothermia); however, by 72 hr after TMT, rats maintained at 22 and 30 degrees C had a significantly elevated Tb. TMT led to marked elevations in GFAP levels, a response that was affected by Ta. In the hippocampus the elevation in GFAP was significantly greater in rats housed at 16 and 30 degrees C. A similar pattern was seen in the midbrain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7566691

  3. Interaction of physical trainings and coffee intakes in fuel utilization during exercise in rats.

    PubMed

    Choi, Eun-Young; Cho, Yun-Ok

    2013-06-01

    This study investigates the impact of exercises, coffee intakes, and physical trainings on fuel utilization in rats. Ninety-six rats were fed a control diet with either water (C) or coffee (CF; 0.12 g freeze-dried instant coffee/100 g body weight/d). Additionally, the animals go through physical training (TC and TCF) or no training (NTC and NTCF) for 4 weeks. For physical training, animals have to exercise on treadmills for 30 minutes (5 d per week, 15° incline, 0.5-0.8 km/h). At the end of week 4, the animals in each group were subdivided into three exercise groups: before exercise (BE), during exercise (DE), and after exercise (AE). The DE rats exercised on treadmills for 1 hour immediately before being sacrificed. Hemoglobin, hematocrit, glucose, glycogen, protein, triglyceride (TG), and free fatty acid (FFA) levels in the plasma, liver, and skeletal muscle of the rats were compared accordingly. Organ weights were also measured. Coffee-training interaction had a significant impact on heart weight, visceral fat, hemoglobin, hematocrit, liver glycogen in DE and AE, and liver triglyceride in DE and AE. Exercise (meaning exercised on a treadmill for 1 hour immediately before being sacrificed) training interaction was significant in liver glycogen, muscle glycogen in control diet and control diet with coffee, FFA and muscle TG levels at control diet with coffee group. Exercise-coffee interactions significantly influenced the FFA with no training groups. Exercise-coffee-training interaction significantly effects on FFA, Liver TG and Muscle TG. Coffee intakes can increase lipolysis during exercising but coffee consumptions delay the recovery of liver glycogen levels in trained rats after exercising. Coffee intakes can increase lipolysis during exercising but coffee consumptions delay the recovery of liver glycogen levels in trained rats after exercising. Coffee can be an effective ergogenic aid during exercise for physically trained rats. PMID:23766878

  4. Interaction of physical trainings and coffee intakes in fuel utilization during exercise in rats

    PubMed Central

    Choi, Eun-Young

    2013-01-01

    This study investigates the impact of exercises, coffee intakes, and physical trainings on fuel utilization in rats. Ninety-six rats were fed a control diet with either water (C) or coffee (CF; 0.12 g freeze-dried instant coffee/100 g body weight/d). Additionally, the animals go through physical training (TC and TCF) or no training (NTC and NTCF) for 4 weeks. For physical training, animals have to exercise on treadmills for 30 minutes (5 d per week, 15° incline, 0.5-0.8 km/h). At the end of week 4, the animals in each group were subdivided into three exercise groups: before exercise (BE), during exercise (DE), and after exercise (AE). The DE rats exercised on treadmills for 1 hour immediately before being sacrificed. Hemoglobin, hematocrit, glucose, glycogen, protein, triglyceride (TG), and free fatty acid (FFA) levels in the plasma, liver, and skeletal muscle of the rats were compared accordingly. Organ weights were also measured. Coffee-training interaction had a significant impact on heart weight, visceral fat, hemoglobin, hematocrit, liver glycogen in DE and AE, and liver triglyceride in DE and AE. Exercise (meaning exercised on a treadmill for 1 hour immediately before being sacrificed) training interaction was significant in liver glycogen, muscle glycogen in control diet and control diet with coffee, FFA and muscle TG levels at control diet with coffee group. Exercise-coffee interactions significantly influenced the FFA with no training groups. Exercise-coffee-training interaction significantly effects on FFA, Liver TG and Muscle TG. Coffee intakes can increase lipolysis during exercising but coffee consumptions delay the recovery of liver glycogen levels in trained rats after exercising. Coffee intakes can increase lipolysis during exercising but coffee consumptions delay the recovery of liver glycogen levels in trained rats after exercising. Coffee can be an effective ergogenic aid during exercise for physically trained rats. PMID:23766878

  5. Uses of vision by rats in play fighting and other close-quarter social interactions.

    PubMed

    Pellis, S M; McKenna, M M; Field, E F; Pellis, V C; Prusky, G T; Whishaw, I Q

    1996-01-01

    Enucleated juvenile rats were compared to sighted juveniles, and tested over six trials. In some of these trials, the vibrissae were clipped and the test chamber was flooded with white noise. Even though the enucleated rats played, they did so in an atypical manner. They tended to initiate more playful and other social contacts, and were more likely to defend themselves if contacted. When they did defend themselves, they adopted behavior patterns that were more likely to evade the partner's attack. In addition, the enucleated rats were hypersensitive to the partner, being more likely to respond defensively when contacted further from the nape (the main play target). All these changes in play fighting by nonsighted rats suggest that the loss of vision leads to motivational changes in activity and reactivity, and so has an indirect effect on play behavior. In addition, direct evidence is also provided to show that vision is used to orient attacks to the nape. When the vibrissae were closely clipped, the sighted rats continued to make direct attacks on the partner's napes, whereas the nonsighted rats did not. Rather, they first contacted some other part of the partner's body and then oriented to the nape. Another test paradigm was used to determine whether vision is used to trigger defensive responses. The rats were partially food deprived as adults and were filmed in a food wrenching and dodging situation where one rat was given a food pellet and the other allowed to steal it. Measurement of the distance at initiation of the lateral swerve away from the approaching partner (i.e., dodge) showed that when the vibrissae are clipped, the sighted rats continued to initiate dodges at the same distance, whereas the nonsighted rats could not. Therefore, vision appears to have an active role in organizing movement sequences of attack and defense in play fighting and other close-quarter interactions. PMID:8778885

  6. Association between Polycystic Ovary Syndrome and Gut Microbiota

    PubMed Central

    Guo, Yanjie; Qi, Yane; Yang, Xuefei; Zhao, Lihui; Wen, Shu; Liu, Yinhui; Tang, Li

    2016-01-01

    Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy in women of reproductive age. It is difficult to treat PCOS because of its complex etiology and pathogenesis. Here, we characterized the roles of gut microbiota on the pathogenesis and treatments in letrozole (a nonsteroidal aromatase inhibitor) induced PCOS rat model. Changes in estrous cycles, hormonal levels, ovarian morphology and gut microbiota by PCR-DGGE and real-time PCR were determined. The results showed that PCOS rats displayed abnormal estrous cycles with increasing androgen biosynthesis and exhibited multiple large cysts with diminished granulosa layers in ovarian tissues. Meanwhile, the composition of gut microbiota in letrozole-treated rats was different from that in the controls. Lactobacillus, Ruminococcus and Clostridium were lower while Prevotella was higher in PCOS rats when compared with control rats. After treating PCOS rats with Lactobacillus and fecal microbiota transplantation (FMT) from healthy rats, it was found that the estrous cycles were improved in all 8 rats in FMT group, and in 6 of the 8 rats in Lactobacillus transplantation group with decreasing androgen biosynthesis. Their ovarian morphologies normalized. The composition of gut microbiota restored in both FMT and Lactobacillus treated groups with increasing of Lactobacillus and Clostridium, and decreasing of Prevotella. These results indicated that dysbiosis of gut microbiota was associated with the pathogenesis of PCOS. Microbiota interventions through FMT and Lactobacillus transplantation were beneficial for the treatments of PCOS rats. PMID:27093642

  7. Ring-Oxidative Biotransformation and Drug Interactions of Propofol in the Livers of Rats

    PubMed Central

    Tai, Yu-Ting; Lin, Yi-Ling; Chang, Chia-Chen; Cherng, Yih-Giun; Don, Ming-Jaw; Chen, Ruei-Ming

    2015-01-01

    Propofol, an intravenous anesthetic agent, is widely used for inducing and maintaining anesthesia during surgical procedures and for sedating intensive care unit patients. In the clinic, rapid elimination is one of the major advantages of propofol. Meanwhile, the biotransformation and drug interactions of propofol in rat livers are still little known. In this study, we evaluated the ring-oxidative metabolism of propofol in phenobarbital-treated rat livers and possible drug interactions. Administration of phenobarbital to male Wistar rats significantly increased levels of hepatic cytochrome P450 (CYP) 2B1/2 and microsomal pentoxyresorufin O-dealkylase (PROD) activity. Analyses by high-performance liquid chromatography and liquid chromatography mass spectroscopy revealed that propofol was metabolized by phenobarbital-treated rat liver microsomes into 4-hydroxypropofol. In comparison, PROD activity and 4-hydroxy-propofol production from propofol metabolism were suppressed by orphenodrine, an inhibitor of CYP2B1/2, and a polyclonal antibody against rat CYP2B1/2 protein. Furthermore, exposure of rats to propofol did not affect the basal or phenobarbital-enhanced levels of hepatic CYP2B1/2 protein. Meanwhile, propofol decreased the dealkylation of pentoxyresorufin by phenobarbital-treated rat liver microsomes in a concentration-dependent manner. Taken together, this study shows that rat hepatic CYP2B1/2 plays a critical role in the ring-oxidative metabolism of propofol into 4-hydroxypropofol, and this anesthetic agent can inhibit CYP2B1/2 activity without affecting protein synthesis. PMID:25710017

  8. Positive interactions between desert granivores: localized facilitation of harvester ants by kangaroo rats.

    PubMed

    Edelman, Andrew J

    2012-01-01

    Facilitation, when one species enhances the environment or performance of another species, can be highly localized in space. While facilitation in plant communities has been intensely studied, the role of facilitation in shaping animal communities is less well understood. In the Chihuahuan Desert, both kangaroo rats and harvester ants depend on the abundant seeds of annual plants. Kangaroo rats, however, are hypothesized to facilitate harvester ants through soil disturbance and selective seed predation rather than competing with them. I used a spatially explicit approach to examine whether a positive or negative interaction exists between banner-tailed kangaroo rat (Dipodomys spectabilis) mounds and rough harvester ant (Pogonomyrmex rugosus) colonies. The presence of a scale-dependent interaction between mounds and colonies was tested by comparing fitted spatial point process models with and without interspecific effects. Also, the effect of proximity to a mound on colony mortality and spatial patterns of surviving colonies was examined. The spatial pattern of kangaroo rat mounds and harvester ant colonies was consistent with a positive interspecific interaction at small scales (<10 m). Mortality risk of vulnerable, recently founded harvester ant colonies was lower when located close to a kangaroo rat mound and proximity to a mound partly predicted the spatial pattern of surviving colonies. My findings support localized facilitation of harvester ants by kangaroo rats, likely mediated through ecosystem engineering and foraging effects on plant cover and composition. The scale-dependent effect of kangaroo rats on abiotic and biotic factors appears to result in greater founding and survivorship of young colonies near mounds. These results suggest that soil disturbance and foraging by rodents can have subtle impacts on the distribution and demography of other species. PMID:22348030

  9. Sexual interactions with unfamiliar females reduce hippocampal neurogenesis among adult male rats.

    PubMed

    Spritzer, M D; Curtis, M G; DeLoach, J P; Maher, J; Shulman, L M

    2016-03-24

    Recent experiments have shown that sexual interactions prior to cell proliferation cause an increase in neurogenesis in adult male rats. Because adult neurogenesis is critical for some forms of memory, we hypothesized that sexually induced changes in neurogenesis may be involved in mate recognition. Sexually naive adult male rats were either exposed repeatedly to the same sexual partner (familiar group) or to a series of novel sexual partners (unfamiliar group), while control males never engaged in sexual interactions. Ovariectomized female rats were induced into estrus every four days. Males were given two injections of 5-bromo-2'-deoxyuridine (BrdU) (200mg/kg) to label proliferating cells, and the first sexual interactions occurred three days later. Males in the familiar and unfamiliar groups engaged in four, 30-min sexual interactions at four-day intervals, and brain tissue was collected the day after the last sexual interaction. Immunohistochemistry followed by microscopy was used to quantify BrdU-labeled cells. Sexual interactions with unfamiliar females caused a significant reduction in neurogenesis in the dentate gyrus compared to males that interacted with familiar females and compared to the control group. The familiar group showed no difference in neurogenesis compared to the control group. Males in the familiar group engaged in significantly more sexual behavior (ejaculations and intromissions) than did males in the unfamiliar group, suggesting that level of sexual activity may influence neurogenesis levels. In a second experiment, we tested whether this effect was unique to sexual interactions by replicating the entire procedure using anestrus females. We found that interactions with unfamiliar anestrus females reduced neurogenesis relative to the other groups, but this effect was not statistically significant. In combination, these results indicate that interactions with unfamiliar females reduce adult neurogenesis and the effect is stronger for sexual

  10. A minor possibility of pharmacokinetic interaction between enoxacin and fenbufen in rats.

    PubMed

    Naora, K; Katagiri, Y; Ichikawa, N; Hayashibara, M; Iwamoto, K

    1990-02-01

    In order to clarify the possibility of pharmacokinetic interaction between quinolone and fenbufen, the plasma concentration-time profiles and serum protein binding of enoxacin, fenbufen and its active metabolite, felbinac, were investigated in rats. The rats were administered an intravenous dose of enoxacin (5 mg/kg) and fenbufen (10 mg/kg) alone or concomitantly. Coadministration with fenbufen tended to prolong the plasma elimination half-life of enoxacin by about 20%, whereas it showed no effect on the area under plasma concentration-time curve, total body clearance or distribution volume of enoxacin. The extent of enoxacin binding to rat serum tended to be slightly reduced by fenbufen in vivo and in vitro. Plasma concentration-time curves, pharmacokinetic parameters and serum protein binding of fenbufen and felbinac were not affected at all by the coadministration with enoxacin. These aspects suggest that there may be only a minor possibility of the pharmacokinetic interaction between enoxacin and fenbufen. PMID:2384853

  11. Neurofibromin interacts with CRMP-2 and CRMP-4 in rat brain

    SciTech Connect

    Lin, Y.-L.; Hsueh, Y.-P.

    2008-05-02

    Neurofibromin, encoded by the neurofibromatosis type 1 (NF1) gene, regulates the Ras and cAMP pathways and plays a role in proliferation and neuronal morphogenesis. The details of the molecular mechanism of neurofibromin action in these processes are still unclear. In this study, immunoprecipitation and proteomics were used to identify novel proteins from rat brain that interact with neurofibromin. Mass spectrometry analysis showed that two proteins, the collapsin response mediator protein-2 (CRMP-2) and propionyl-CoA carboxylase alpha chain (PCCA), associated with neurofibromin. Immunoprecipitation-immunoblotting analysis confirmed the interactions between neurofibromin and CRMP-2 and CRMP-4, but not CRMP-1, in rat brain. CDK5, a kinase that regulates CRMP-2 in axonal outgrowth, was required for the interaction between neurofibromin and CRMP-2. Since both neurofibromin and CRMP proteins are involved in proliferation and axonal morphogenesis, these results suggest that the interaction with CRMPs contributes to the function of neurofibromin in tumorigenesis and neuronal morphogenesis.

  12. Cryopreservation of ovaries from neonatal marmoset monkeys.

    PubMed

    Motohashi, Hideyuki H; Ishibashi, Hidetoshi

    2016-07-29

    The ovary of neonatal nonhuman primates contains the highest number of immature oocytes, but its cryopreservation has not yet been sufficiently investigated in all life stages. In the current study, we investigated cryodamage after vitrification/warming of neonatal ovaries from a nonhuman primate, the common marmoset (Callithrix jacchus). A Cryotop was used for cryopreservation of whole ovaries. The morphology of the vitrified/warmed ovaries was found to be equivalent to that of fresh ovaries. No significant difference in the number of oocytes retaining normal morphology per unit area in histological sections was found between the two groups. In an analysis of dispersed cells from the ovaries, however, the cell viability of the vitrified/warmed group tended to be decreased. The results of a comet assay showed no significant differences in DNA damage. These results show that cryopreservation of neonatal marmoset ovaries using vitrification may be useful as a storage system for whole ovaries. PMID:26876597

  13. Cryopreservation of ovaries from neonatal marmoset monkeys

    PubMed Central

    Motohashi, Hideyuki H.; Ishibashi, Hidetoshi

    2016-01-01

    The ovary of neonatal nonhuman primates contains the highest number of immature oocytes, but its cryopreservation has not yet been sufficiently investigated in all life stages. In the current study, we investigated cryodamage after vitrification/warming of neonatal ovaries from a nonhuman primate, the common marmoset (Callithrix jacchus). A Cryotop was used for cryopreservation of whole ovaries. The morphology of the vitrified/warmed ovaries was found to be equivalent to that of fresh ovaries. No significant difference in the number of oocytes retaining normal morphology per unit area in histological sections was found between the two groups. In an analysis of dispersed cells from the ovaries, however, the cell viability of the vitrified/warmed group tended to be decreased. The results of a comet assay showed no significant differences in DNA damage. These results show that cryopreservation of neonatal marmoset ovaries using vitrification may be useful as a storage system for whole ovaries. PMID:26876597

  14. Distribution and responsiveness of rat anti-Muellerian hormone during ovarian development and VCD-induced ovotoxicity

    SciTech Connect

    Mark-Kappeler, Connie J.; Sen, Nivedita; Keating, Aileen F.; Sipes, I. Glenn; Hoyer, Patricia B.

    2010-11-15

    Anti-Muellerian hormone (AMH) is produced by granulosa cells in primary to small antral follicles of the adult ovary and helps maintain primordial follicles in a dormant state. The industrial chemical, 4-vinylcyclohexene diepoxide (VCD) causes specific ovotoxicity in primordial and small primary follicles of mice and rats. Previous studies suggest that this ovotoxicity involves acceleration of primordial to primary follicle recruitment via interactions with the Kit/Kit ligand signaling pathway. Because of its accepted role in inhibiting primordial follicle recruitment, the present study was designed to investigate a possible interaction between AMH and VCD-induced ovotoxicity. Protein distribution of AMH was compared in neonatal and adult F344 rat ovaries. AMH protein was visualized by immunofluorescence microscopy in large primary and secondary follicles of the adult ovary, but in small primary follicles in neonatal rat ovaries. In cultured postnatal day (PND) 4 F344 rat ovaries, VCD exposure (30 {mu}M, 2-8 days) decreased (P < 0.05) AMH mRNA (d4-8) and protein (d6-8). Recombinant AMH (100-400 mg/ml) in PND4 ovaries cultured 8 days {+-} VCD (30 {mu}M) caused an increase (P < 0.05) in primordial, and a decrease (P < 0.05) in small primary follicles, supporting that AMH retarded primordial follicle recruitment. However, no concentration of AMH had an effect on VCD-induced ovotoxicity. Whereas, VCD caused a reduction in expression of AMH (d4-d8), it followed previously reported initial disruptions in Kit signaling induced by VCD (d2). Thus, collectively, these results do not support a mechanism whereby VCD causes ovotoxicity via generalized activation of primordial follicle recruitment, but instead provide further support for the specificity of other intracellular mechanisms involved in VCD-induced ovotoxicity.

  15. Distribution and responsiveness of rat anti-Müllerian hormone during ovarian development and VCD-induced ovotoxicity.

    PubMed

    Mark-Kappeler, Connie J; Sen, Nivedita; Keating, Aileen F; Sipes, I Glenn; Hoyer, Patricia B

    2010-11-15

    Anti-Müllerian hormone (AMH) is produced by granulosa cells in primary to small antral follicles of the adult ovary and helps maintain primordial follicles in a dormant state. The industrial chemical, 4-vinylcyclohexene diepoxide (VCD) causes specific ovotoxicity in primordial and small primary follicles of mice and rats. Previous studies suggest that this ovotoxicity involves acceleration of primordial to primary follicle recruitment via interactions with the Kit/Kit ligand signaling pathway. Because of its accepted role in inhibiting primordial follicle recruitment, the present study was designed to investigate a possible interaction between AMH and VCD-induced ovotoxicity. Protein distribution of AMH was compared in neonatal and adult F344 rat ovaries. AMH protein was visualized by immunofluorescence microscopy in large primary and secondary follicles of the adult ovary, but in small primary follicles in neonatal rat ovaries. In cultured postnatal day (PND) 4 F344 rat ovaries, VCD exposure (30 μM, 2-8 days) decreased (P<0.05) AMH mRNA (d4-8) and protein (d6-8). Recombinant AMH (100-400 mg/ml) in PND4 ovaries cultured 8 days±VCD (30 μM) caused an increase (P<0.05) in primordial, and a decrease (P<0.05) in small primary follicles, supporting that AMH retarded primordial follicle recruitment. However, no concentration of AMH had an effect on VCD-induced ovotoxicity. Whereas, VCD caused a reduction in expression of AMH (d4-d8), it followed previously reported initial disruptions in Kit signaling induced by VCD (d2). Thus, collectively, these results do not support a mechanism whereby VCD causes ovotoxicity via generalized activation of primordial follicle recruitment, but instead provide further support for the specificity of other intracellular mechanisms involved in VCD-induced ovotoxicity. PMID:20816688

  16. [Laparoscopic fenestration of the ovaries].

    PubMed

    Nalbanski, B; Pŭnevska, M; Veltova, L

    1997-01-01

    The authors have performed an ovary fenestration in 220 women with primary or secondary amenorrhea. This was made with the help of instrumentation for laparoscopy and a monopolar electrodiathermic coagulator with differently shaped endings. The power supply was provided from Martin Elektrotom 2000. A spontaneous recovers of the menstruation was achieved in 36.84% of the cases as a result of the endoscopic intervention. A follows up pregnancy was achieved in 12.4% of the women. Considering the obtained results, the authors recommend the use of a laparoscopic ovary fenestration when a women with ovarian cysts is treated. PMID:9471896

  17. HEPATOTOXIC INTERACTIONS OF ETHANOL WITH ALLYL ALCOHOL OR CARBON TETRACHLORIDE IN RATS

    EPA Science Inventory

    To assess interactive toxicity following subacute, concurrent chemical exposure, male Fischer-344 rats, approximately 70 days of age, were given ethanol at 0, 0.'05, 0.1, 0.2, or 0.5 ml/kg in corn oil daily by gavage for 14 days ([TON group), or the same levels of ethanol with 21...

  18. NATURE OF BINDING INTERACTION OF SELECTED CHEMICALS WITH RAT ESTROGEN RECEPTORS

    EPA Science Inventory

    The US EPA is currently validating a rat uterine estrogen receptor (ER) binding assay as part of the Tier 1 Screening Battery for the Endocrine Disruptor Program. An eventual goal is to use interactive data to create computerized structure-activity models. However, more informati...

  19. Pharmacokinetic Interaction between Nevirapine and Nortriptyline in Rats: Inhibition of Nevirapine Metabolism by Nortriptyline

    PubMed Central

    Usach, Iris; Melis, Virginia; Gandía, Patricia

    2014-01-01

    One of the most frequent comorbidities of HIV infection is depression, with a lifetime prevalence of 22 to 45%. Therefore, it was decided to study a potential pharmacokinetic interaction between the nonnucleoside reverse transcriptase inhibitor nevirapine (NVP) and the tricyclic antidepressant nortriptyline (NT). NVP and NT were administered to rats either orally, intraduodenally, or intravenously, and the changes in plasma levels and pharmacokinetic parameters were analyzed. Experiments with rat and human hepatic microsomes were carried out to evaluate the inhibitory effects of NT on NVP metabolism. NVP plasma concentrations were significantly higher when this drug was coadministered with NT. The maximum plasma concentrations of NVP were increased 2 to 5 times and the total plasma clearance was decreased 7-fold in the presence of NT. However, statistically significant differences in the pharmacokinetic parameters of NT in the absence and presence of NVP were not found. In vitro studies with rat and human hepatic microsomes confirmed the inhibition of NVP hepatic metabolism by NT in a concentration-dependent way, with the inhibition being more intense in the case of rat microsomes. In conclusion, a pharmacokinetic interaction between NVP and NT was detected. This interaction was a consequence of the inhibition of hepatic metabolism of NVP by NT. In vivo human studies are required to evaluate the effects of this interaction on the pharmacokinetics of NVP before it can be taken into account for patients receiving NVP. PMID:25224004

  20. (35S)methionine interaction with rat liver tRNA and effect of chemical carcinogens

    SciTech Connect

    Kanduc, D.; Quagliariello, E. )

    1991-07-01

    The interaction of (35S)methionine with hepatic tRNA in normal, carcinogen-treated, and partially hepatectomized rats was studied. tRNA was preferentially labeled following (35S)methionine (1.6 mCi, 25 mg/kg body wt) administration by intraperitoneal injection. The extent of (35S)methionine-tRNA interaction was impaired by partial hepatectomy and by conditions having a carcinogenic potential.

  1. Multisensory interaction mediates the social transmission of avoidance in rats: dissociation from social transmission of fear.

    PubMed

    Masuda, Akira; Narikiyo, Kimiya; Someya, Nami; Aou, Shuji

    2013-09-01

    Social interaction enables animals to transmit various types of sensory information that can modulate learned avoidance behavior and fear responses, which are important to survival. We previously reported that, under a passive avoidance paradigm, avoidance behavior is facilitated when a rat observes another rat (demonstrator) receiving a shock when performing a specific behavior. However, the sensory mechanisms underlying this 'social facilitation of avoidance' are not well understood. The present study examined the role of sensory pathways for social transmission of avoidance, focusing on the olfactory and visual systems. The olfactory ability of observer rats was blocked by an intranasal application of ZnSO4, and their visual ability was blocked by an opaque partition placed between observer and demonstrator rats. We found that blocking either olfactory or visual input drastically diminished the social transmission of avoidance. Interestingly the social transmission of fear responses remained intact even when olfactory or visual information was blocked. These results indicate that the social transmission of avoidance is mediated not by any single sensory modality but by multisensory interaction in rats, suggesting a distinct sensory mechanism from that underlying the social transmission of fear. PMID:23769998

  2. Prenatal stress and stress coping style interact to predict metabolic risk in male rats.

    PubMed

    Boersma, Gretha J; Moghadam, Alexander A; Cordner, Zachary A; Tamashiro, Kellie L

    2014-04-01

    Both prenatal stress (PNS) exposure and a passive stress-coping style have been identified as risk factors for insulin resistance in rats. In the current study, we test the hypothesis that PNS and stress-coping style may interact in predicting susceptibility for metabolic disease. To test this hypothesis, adult male control and PNS offspring were behaviorally characterized using a defensive burying test to have either a passive or proactive stress-coping style. In adulthood, all rats were fed either a standard chow or a high-fat diet for 3 weeks. After 3 weeks of diet exposure, glucose and insulin levels were assessed during an oral glucose tolerance test. Under high-fat diet conditions, PNS rats display elevated glucose and insulin responses to the oral glucose tolerance test, indicative of glucose intolerance. Interestingly, these effects of PNS were far more pronounced in rats characterized by a passive stress-coping style. Additionally, the passively coping PNS rats also gained more weight on the high-fat diet than all other rats tested. This observation suggests that a stressful prenatal environment in combination with a passive stress-coping strategy may prime an individual to be sensitive to diet-induced obesity and type 2 diabetes. PMID:24467745

  3. Interaction of macrolide antibiotics with intestinally expressed human and rat organic anion-transporting polypeptides.

    PubMed

    Lan, Tian; Rao, Anuradha; Haywood, Jamie; Davis, Charles B; Han, Chao; Garver, Eric; Dawson, Paul A

    2009-12-01

    The macrolide antibiotics azithromycin and clarithromycin are large molecular weight compounds that exhibit moderate to excellent oral bioavailability in preclinical species and humans. Previous concomitant dosing studies in rats using rifamycin SV, a general organic anion-transporting polypeptide (OATP) inhibitor, suggested that the high oral absorption of azithromycin and clarithromycin may be caused by facilitative uptake by intestinal Oatps. In this study, we used OATP/Oatp-expressing cells to investigate the interaction of macrolides with rat Oatp1a5, human OATP1A2, and human/rat OATP2B1/Oatp2b1. These experiments showed that azithromycin and clarithromycin were potent inhibitors of rat Oatp1a5-mediated taurocholate uptake with apparent inhibitor constant (K(i)) values of 3.3 and 2.4 microM, respectively. The macrolides functioned as noncompetitive inhibitors but were not transport substrates for rat Oatp1a5, as assessed by direct uptake measurements of radiolabeled azithromycin and clarithromycin. cis-Inhibition and direct uptake studies further showed that azithromycin and clarithromycin were only very weak inhibitors and not substrates for human OATP1A2 and human/rat OATP2B1/Oatp2b1. In summary, these results indicate that the macrolides azithromycin and clarithromycin potently inhibit rat Oatp1a5 but do not significantly interact with OATP1A2 and OATP2B1/Oatp2b1. These intestinally expressed OATP/Oatp(s) are not responsible for the postulated facilitative uptake of azithromycin and clarithromycin, and alternative facilitative pathways must exist for their intestinal absorption. PMID:19741038

  4. Pharmacokinetics Interaction between Imatinib and Genistein in Rats

    PubMed Central

    Wang, Zhe; Wang, Li; Xia, Meng-ming; Sun, Wei; Huang, Cheng-ke; Cui, Xiao; Hu, Guo-xin; Lian, Qing-quan; Wang, Zeng-shou

    2015-01-01

    The objective of this work was to investigate the effect of orally administered genistein on the pharmacokinetics of imatinib and N-desmethyl imatinib in rats. Twenty-five healthy male SD (Sprague-Dawley) rats were randomly divided into five groups: A group (control group), B group (multiple dose of 100 mg/kg genistein for consecutive 15 days), C group (multiple dose of 50 mg/kg genistein for consecutive 15 days), D group (a single dose of 100 mg/kg genistein), and E group (a single dose of 50 mg/kg genistein). A single dose of imatinib is administered orally 30 min after administration of genistein (100 mg/kg or 50 mg/kg). The pharmacokinetic parameters of imatinib and N-desmethyl imatinib were calculated by DAS 3.0 software. The multiple dose of 100 mg/kg or 50 mg/kg genistein significantly (P < 0.05) decreased the AUC0−t and Cmax of imatinib. AUC0−t and the Cmax of N-desmethyl imatinib were also increased, but without any significant difference. However, the single dose of 100 mg/kg or 50 mg/kg genistein has no effect on the pharmacokinetics of imatinib and N-desmethyl imatinib. Those results indicated that multiple dose of genistein (100 mg/kg or 50 mg/kg) induces the metabolism of imatinib, while single dose of genistein has no effect. PMID:25629045

  5. Inflammatory bowel disease in rats: Bacterial and chemical interaction

    PubMed Central

    Hussein, Inaya Abdallah Hajj; Tohme, Rania; Barada, Kassem; Mostafa, Mostafa Hassan; Freund, Jean-Noel; Jurjus, Rosalyn A; Karam, Walid; Jurjus, Abdo

    2008-01-01

    AIM: To develop a novel model of colitis in rats, using a combination of iodoacetamide and enteropathogenic E. coli (EPEC), and to elucidate the pathophysiologic processes implicated in the development of ulcerative colitis (UC). METHODS: Male Sprague-Dawley rats (n = 158) were inoculated intrarectally on a weekly basis with 4 different combinations: (a) 1% methylcellulose (MC), (b) 100 μL of 6% iodoacetamide (IA) in 1% MC, (c) 200 μL containing 4 × 108 colony factor units (CFU) of EPEC, and (d) combined treatment of (IA) followed by bacteria (B) after 2 d. Thirty days post treatment, each of the four groups was divided into two subgroups; the inoculation was stopped for one subgroup and the other subgroup continued with biweekly inoculation until the end of the experiment. Colitis was evaluated by the clinical course of the disease, the macroscopic and microscopic alterations, activity of myeloperoxidase (MPO), and by TNF-α gene expression. RESULTS: Findings indicative of UC were seen in the combined treatment (IA + B) as well as the IA continued treatment groups: the animals showed slow rate of increase in body weight, diarrhea, bloody stools, high colonic ulcer score, as well as histological alterations characteristic of UC, with an extensive inflammatory reaction. During the course of the experiment, the MPO activity was consistently elevated and the TNF-α gene expression was upregulated compared to the control animals. CONCLUSION: The experimental ulcerative colitis model used in the present study resembles, to a great extent, the human disease. It is reproducible with characteristics indicative of chronicity. PMID:18609687

  6. APOPTOSIS IN WHOLE MOUSE OVARIES

    EPA Science Inventory

    Apoptosis in Whole Mouse Ovaries
    Robert M. Zucker Susan C. Jeffay and Sally D. Perreault
    Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, 27711.

  7. Interactions of ozone and antineoplastic drugs on rat lung fibroblasts and Walker rat carcinoma cells

    SciTech Connect

    Wenzel, D.G.; Morgan, D.L.

    1983-05-01

    Cultured rat lung fibroblasts (F-cells) and Walker rat carcinoma cells (WRC-cells) labeled with /sup 51/Cr were exposed to the following antitumor drugs alone or with O/sub 3/: carmustine (BCNU), doxorubicin (Dox), cisplatin (CPt), mitomycin C (Mit C) or vitamin K/sub 3/ (Vit K). Release of /sup 51/Cr (cell injury) was greater for F-cells than WRC-cells with any single treatment. Pretreatment with any drug (400 microM), except for Vit K with WRC-cells, did not significantly increase O/sub 3/-induced loss of /sup 51/Cr. Co-exposure of F-cells to drugs and O/sub 3/ resulted in a marked potentiation of O/sub 3/-induced injury with Vit K, and an inhibition with Dox.

  8. Characterizing olfactory binary mixture interactions in Fischer 344 rats using behavioral reaction times.

    PubMed

    Yoder, Wendy M; Gaynor, Leslie; Windham, Ethan; Lyman, Michelle; Munizza, Olivia; Setlow, Barry; Bizon, Jennifer L; Smith, David W

    2015-06-01

    Response times provide essential subthreshold perceptual data that extend beyond accuracy alone. Behavioral reaction times (RTs) were used to characterize rats' ability to detect individual odorants in a series of complimentary binary odorant mixture ratios. We employed an automated, liquid-dilution olfactometer to train Fischer 344 rats (N = 8) on an odor identification task using nonreinforced probe trials. Binary mixture ratios composed of aliphatic odorants (citral and octanol) were arranged such that relative contributions of the 2 components varied systematically by a factor of 1% (v/v). Odorant concentrations for the target (S+), control (S-), and mixture (S+:S-) odorants were presented relative to threshold for each rat. Rats were initially trained to respond by licking at a spout to obtain liquid reward for either citral or octanol as the reinforced target (S+) odorant. After achieving 100% accuracy, rats were transferred to variable ratio (VR 2) reinforcement for correct responding. Nonreinforced probe trials (2 per block of 22 trials) were tested for each mixture ratio and recorded as either S+ (rats lick-responded in the presence of the mixture) or S- (rats refrained from licking), thereby indicating detection of the trained, S+ odorant. To determine the perceived salience for each ratio, RTs (latency from odorant onset to lick response) were recorded for each trial. Consistent with previous studies, RTs for both odorants were shortest (~150-200ms) when the probe trials consisted of a single, monomolecular component. Binary mixtures that contained as little as 1% of the S-, nontarget odorant, however, were sufficiently different perceptually to increase behavioral RTs (i.e., rats hesitated longer before responding); RTs changed systematically as a function of the binary ratio. Interestingly, the rate of RT change was dependent on which odorant served as the S+, suggesting an asymmetric interaction between the 2 odorants. The data demonstrate the value

  9. Food-drug interaction of tacrolimus with pomelo, ginger, and turmeric juice in rats.

    PubMed

    Egashira, Kanoko; Sasaki, Hitoshi; Higuchi, Shun; Ieiri, Ichiro

    2012-01-01

    Tacrolimus is a well-known potent immunosuppressant agent, which has various drug-drug or food-drug interactions. Previously, we found a renal transplant recipient who increased tacrolimus blood concentrations after ingestion of pomelo as a rare case. So, we investigated the effect of pomelo after its administration for one day or 3 consecutive days on the pharmacokinetics of tacrolimus in rats. We also confirmed the effects of grapefruit, turmeric, and ginger. The tacrolimus blood concentrations of the rats pre-treated with 100% pomelo juice were significantly higher than those pre-treated with water. On the other hand, the tacrolimus blood concentrations of the rats pre-treated with 50% pomelo juice were not significantly different from those pre-treated with water. The pomelo-tacrolimus interaction showed concentration dependency. Even low concentration of pomelo juice could enhance the blood concentrations of tacrolimus by repeated administration. The inhibitory effect of 100% pomelo juice disappeared 3 days after intake. The AUC values of tacrolimus in the rats pre-treated with grapefruit juice, ginger juice, and turmeric juice were significantly larger than those pre-treated with water. We could confirm the pomelo-tacrolimus interaction, which we discovered in a case study, quantitatively. We newly found the influence of turmeric and ginger on tacrolimus pharmacokinetics, comparable to pomelo. PMID:22123127

  10. Features of Polycystic Ovary Syndrome in adolescence

    PubMed Central

    Tsikouras, P; Spyros, L; Manav, B; Zervoudis, S; Poiana, C; Nikolaos, T; Petros, P; Dimitraki, M; Koukouli, C; Galazios, G; von Tempelhoff, GF

    2015-01-01

    Rationale: To elucidate the prepubertal risk factors associated with the development of Polycystic Ovary Syndrome (PCOS) and determine the special clinical manifestations of the syndrome in this transitional time of a woman’s life. Objective: To propose therapeutic targets and regimens, not only to prevent the long-term complications of the syndrome, but also to improve the self-esteem of a young girl who matures into womanhood. Methods and Results: A systematic review of literature was performed through electronic database searches (Pubmed, Medline and Embase). Studies published in English-language, peer-reviewed journals from 1996 to 2013 were included. The selected studies focused on the risk factors, the unique features and treatment options of the PCOS in puberty. The pathogenesis of the PCOS was hypothesized to be based on interactions between genetic and certain environmental factors. The diagnosis was usually difficult in young girls. The syndrome was related to a greater risk of future infertility, type II diabetes mellitus, the metabolic syndrome and cardiovascular disease. Early treatment was crucial to prevent the long-term complications of the syndrome, especially infertility and cardiovascular disease. Discussion:The recognition of the early signs of PCOS during or even before adolescence is of great importance. It is essential to establish the correct diagnosis for PCOS and rule out other causes of androgen excess in young women with hyperandrogenism. The type of treatment applied should be considered on an individual basis. Abbreviations: PCOS = Polycystic Ovary Syndrome PMID:26351529

  11. An autoradiographic map of (3H)diprenorphine binding in rat brain: effects of social interaction

    SciTech Connect

    Panksepp, J.; Bishop, P.

    1981-10-01

    (3H)Diprenorphine binding was analyzed autoradiographically in the brains of 33 day old rat pups. A photographic atlas of diprenorphine binding in the coronal plane is provided to highlight the dispersion of opioid receptor systems through the brain. To determine whether brain opioid release may be induced by social interactions, half the animals were sacrificed following a 30 min period of social interaction while the other half were sacrificed following 30 min of social isolation. Opioid binding was higher in isolate-tested animals than socially-tested ones, suggesting that social interaction may promote endogenous brain opioid release.

  12. Striatal adenosine-cannabinoid receptor interactions in rats over-expressing adenosine A2A receptors.

    PubMed

    Chiodi, Valentina; Ferrante, Antonella; Ferraro, Luca; Potenza, Rosa Luisa; Armida, Monica; Beggiato, Sarah; Pèzzola, Antonella; Bader, Michael; Fuxe, Kjell; Popoli, Patrizia; Domenici, Maria Rosaria

    2016-03-01

    Adenosine A2A receptors (A2 A Rs) and cannabinoid CB1 receptors (CB1 Rs) are highly expressed in the striatum, where they functionally interact and form A2A /CB1 heteroreceptor complexes. We investigated the effects of CB1 R stimulation in a transgenic rat strain over-expressing A2 A Rs under the control of the neural-specific enolase promoter (NSEA2A rats) and in age-matched wild-type (WT) animals. The effects of the CB1 R agonist WIN 55,212-2 (WIN) were significantly lower in NSEA2A rats than in WT animals, as demonstrated by i) electrophysiological recordings of synaptic transmission in corticostriatal slices; ii) the measurement of glutamate outflow from striatal synaptosomes and iii) in vivo experiments on locomotor activity. Moreover, while the effects of WIN were modulated by both A2 A R agonist (CGS 21680) and antagonists (ZM 241385, KW-6002 and SCH-442416) in WT animals, the A2 A R antagonists failed to influence WIN-mediated effects in NSEA2A rats. The present results demonstrate that in rats with genetic neuronal over-expression of A2 A Rs, the effects mediated by CB1 R activation in the striatum are significantly reduced, suggesting a change in the stoichiometry of A2A and CB1 receptors and providing a strategy to dissect the involvement of A2 A R forming or not forming heteromers in the modulation of striatal functions. These findings add additional evidence for the existence of an interaction between striatal A2 A Rs and CB1 Rs, playing a fundamental role in the regulation of striatal functions. We studied A2A -CB1 receptor interaction in transgenic rats over-expressing adenosine A2A receptors under the control of the neuron-specific enolase promoter (NSEA2A ). In these rats, we demonstrated a reduced effect of the CB1 receptor agonist WIN 55,212-2 in the modulation of corticostriatal synaptic transmission and locomotor activity, while CB1 receptor expression level did not change with respect to WT rats. A reduction in the expression of A2A -CB1

  13. Opioid-glutamate interactions in rat locus coeruleus neurons.

    PubMed

    Oleskevich, S; Clements, J D; Williams, J T

    1993-09-01

    1. The effect of mu-opioids on the glutamate response was investigated in rat locus coeruleus (LC) neurons by intracellular recording in the brain slice preparation. Glutamate responses were evoked by bath application of selective glutamate agonists, glutamate iontophoresis, and stimulation of excitatory afferents. 2. The mu-opioid agonist D-Ala2-MePhe4-Gly-ol5-enkephalin (DAMGO; 1 microM) potentiated the response to bath application of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid by 91 and 142%, respectively, in slices cut in the horizontal plane. The mechanism of action of this effect was investigated under conditions that limited the DAMGO-induced hyperpolarization and improved the space clamp of the neuron through 1) addition of barium, 2) increase in extracellular potassium concentration, 3) sectioning of the LC in the coronal plane, and 4) addition of carbenoxolone. Each experimental manipulation decreased the DAMGO outward current and reduced the mu-opioid potentiation of the glutamate response. The results suggest that the mu-opioid-mediated potentiation of the glutamate response is dependent on membrane hyperpolarization. 3. Neither forskolin nor the phorbol ester 4b-phorbol 12,13-dibutyrate (PDBu) altered the glutamate-mediated inward currents. The potentiation of the glutamate response by DAMGO was not affected by PDBu. 4. The mu-opioids DAMGO and [met]5enkephalin (10 microM) did not significantly affect the NMDA receptor-mediated depolarization (mean 14%) evoked by local application of glutamate but inhibited the NMDA receptor-mediated synaptic potential (mean 25%).(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7693886

  14. Erythromycin potentiates PR interval prolonging effect of verapamil in the rat: A pharmacodynamic drug interaction

    SciTech Connect

    Dakhel, Yaman; Jamali, Fakhreddin . E-mail: fjamali@ualberta.ca

    2006-07-01

    Calcium channel blockers and macrolide antibiotics account for many drug interactions. Anecdotal reports suggest interactions between the two resulting in severe side effects. We studied the interaction between verapamil and erythromycin in the rat to see whether it occurs at the pharmacokinetics or pharmacodynamic level. Adult male Sprague-Dawley rats received doses of 1 mg/kg verapamil or 100 mg/kg erythromycin alone or in combination (n = 6/group). Serial blood samples (0-6 h) were taken for determination of the drug concentrations using HPLC. Electrocardiograms were recorded (0-6 h) through subcutaneously inserted lead II. Binding of the drugs to plasma proteins was studied using spiked plasma. Verapamil prolonged PR but not QT interval. Erythromycin prolonged QT but not PR interval. The combination resulted in a significant increase in PR interval prolongation and AV node blocks but did not further prolong QT interval. Pharmacokinetics and protein binding of neither drug were altered by the other. Our rat data confirm the anecdotal human case reports that combination of erythromycin and verapamil can result in potentiation of the cardiovascular response. The interaction appears to be at the pharmacodynamic rather than pharmacokinetic level hence may be extrapolated to other calcium channel antagonists.

  15. Characterizing Olfactory Binary Mixture Interactions in Fischer 344 Rats Using Behavioral Reaction Times

    PubMed Central

    Yoder, Wendy M.; Gaynor, Leslie; Windham, Ethan; Lyman, Michelle; Munizza, Olivia; Setlow, Barry; Bizon, Jennifer L.

    2015-01-01

    Response times provide essential subthreshold perceptual data that extend beyond accuracy alone. Behavioral reaction times (RTs) were used to characterize rats’ ability to detect individual odorants in a series of complimentary binary odorant mixture ratios. We employed an automated, liquid-dilution olfactometer to train Fischer 344 rats (N = 8) on an odor identification task using nonreinforced probe trials. Binary mixture ratios composed of aliphatic odorants (citral and octanol) were arranged such that relative contributions of the 2 components varied systematically by a factor of 1% (v/v). Odorant concentrations for the target (S+), control (S−), and mixture (S+:S−) odorants were presented relative to threshold for each rat. Rats were initially trained to respond by licking at a spout to obtain liquid reward for either citral or octanol as the reinforced target (S+) odorant. After achieving 100% accuracy, rats were transferred to variable ratio (VR 2) reinforcement for correct responding. Nonreinforced probe trials (2 per block of 22 trials) were tested for each mixture ratio and recorded as either S+ (rats lick-responded in the presence of the mixture) or S− (rats refrained from licking), thereby indicating detection of the trained, S+ odorant. To determine the perceived salience for each ratio, RTs (latency from odorant onset to lick response) were recorded for each trial. Consistent with previous studies, RTs for both odorants were shortest (~150–200ms) when the probe trials consisted of a single, monomolecular component. Binary mixtures that contained as little as 1% of the S−, nontarget odorant, however, were sufficiently different perceptually to increase behavioral RTs (i.e., rats hesitated longer before responding); RTs changed systematically as a function of the binary ratio. Interestingly, the rate of RT change was dependent on which odorant served as the S+, suggesting an asymmetric interaction between the 2 odorants. The data demonstrate

  16. A 3D-Video-Based Computerized Analysis of Social and Sexual Interactions in Rats

    PubMed Central

    Matsumoto, Jumpei; Urakawa, Susumu; Takamura, Yusaku; Malcher-Lopes, Renato; Hori, Etsuro; Tomaz, Carlos; Ono, Taketoshi; Nishijo, Hisao

    2013-01-01

    A large number of studies have analyzed social and sexual interactions between rodents in relation to neural activity. Computerized video analysis has been successfully used to detect numerous behaviors quickly and objectively; however, to date only 2D video recording has been used, which cannot determine the 3D locations of animals and encounters difficulties in tracking animals when they are overlapping, e.g., when mounting. To overcome these limitations, we developed a novel 3D video analysis system for examining social and sexual interactions in rats. A 3D image was reconstructed by integrating images captured by multiple depth cameras at different viewpoints. The 3D positions of body parts of the rats were then estimated by fitting skeleton models of the rats to the 3D images using a physics-based fitting algorithm, and various behaviors were recognized based on the spatio-temporal patterns of the 3D movements of the body parts. Comparisons between the data collected by the 3D system and those by visual inspection indicated that this system could precisely estimate the 3D positions of body parts for 2 rats during social and sexual interactions with few manual interventions, and could compute the traces of the 2 animals even during mounting. We then analyzed the effects of AM-251 (a cannabinoid CB1 receptor antagonist) on male rat sexual behavior, and found that AM-251 decreased movements and trunk height before sexual behavior, but increased the duration of head-head contact during sexual behavior. These results demonstrate that the use of this 3D system in behavioral studies could open the door to new approaches for investigating the neuroscience of social and sexual behavior. PMID:24205238

  17. A 3D-video-based computerized analysis of social and sexual interactions in rats.

    PubMed

    Matsumoto, Jumpei; Urakawa, Susumu; Takamura, Yusaku; Malcher-Lopes, Renato; Hori, Etsuro; Tomaz, Carlos; Ono, Taketoshi; Nishijo, Hisao

    2013-01-01

    A large number of studies have analyzed social and sexual interactions between rodents in relation to neural activity. Computerized video analysis has been successfully used to detect numerous behaviors quickly and objectively; however, to date only 2D video recording has been used, which cannot determine the 3D locations of animals and encounters difficulties in tracking animals when they are overlapping, e.g., when mounting. To overcome these limitations, we developed a novel 3D video analysis system for examining social and sexual interactions in rats. A 3D image was reconstructed by integrating images captured by multiple depth cameras at different viewpoints. The 3D positions of body parts of the rats were then estimated by fitting skeleton models of the rats to the 3D images using a physics-based fitting algorithm, and various behaviors were recognized based on the spatio-temporal patterns of the 3D movements of the body parts. Comparisons between the data collected by the 3D system and those by visual inspection indicated that this system could precisely estimate the 3D positions of body parts for 2 rats during social and sexual interactions with few manual interventions, and could compute the traces of the 2 animals even during mounting. We then analyzed the effects of AM-251 (a cannabinoid CB1 receptor antagonist) on male rat sexual behavior, and found that AM-251 decreased movements and trunk height before sexual behavior, but increased the duration of head-head contact during sexual behavior. These results demonstrate that the use of this 3D system in behavioral studies could open the door to new approaches for investigating the neuroscience of social and sexual behavior. PMID:24205238

  18. Interaction between nanoparticles generated by zinc chloride treatment and oxidative responses in rat liver.

    PubMed

    Azzouz, Inès; Trabelsi, Hamdi; Hanini, Amel; Ferchichi, Soumaya; Tebourbi, Olfa; Sakly, Mohsen; Abdelmelek, Hafedh

    2014-01-01

    The aim of the present study was to investigate the interaction of zinc chloride (3 mg/kg, intraperitoneally [ip]) in rat liver in terms of the biosynthesis of nanoparticles. Zinc treatment increased zinc content in rat liver. Analysis of fluorescence revealed the presence of red fluorescence in the liver following zinc treatment. Interestingly, the co-exposure to zinc (3 mg/kg, ip) and selenium (0.20 mg/L, per os [by mouth]) led to a higher intensity of red fluorescence compared to zinc-treated rats. In addition, X-ray diffraction measurements carried out on liver fractions of zinc-treated rats point to the biosynthesis of zinc sulfide and/or selenide nanocomplexes at nearly 51.60 nm in size. Moreover, co-exposure led to nanocomplexes of about 72.60 nm in size. The interaction of zinc with other mineral elements (S, Se) generates several nanocomplexes, such as ZnS and/or ZnSe. The nanocomplex ZnX could interact directly with enzyme activity or indirectly by the disruption of mineral elements' bioavailability in cells. Subacute zinc or selenium treatment decreased malondialdehyde levels, indicating a drop in lipid peroxidation. In addition, antioxidant enzyme assays showed that treatment with zinc or co-treatment with zinc and selenium increased the activities of glutathione peroxidase, catalase, and superoxide dismutase. Consequently, zinc complexation with sulfur and/or selenium at nanoscale level could enhance antioxidative responses, which is correlated to the ratio of number of ZnX nanoparticles (X=sulfur or X=selenium) to malondialdehyde level in rat liver. PMID:24403828

  19. Interaction between nanoparticles generated by zinc chloride treatment and oxidative responses in rat liver

    PubMed Central

    Azzouz, Inès; Trabelsi, Hamdi; Hanini, Amel; Ferchichi, Soumaya; Tebourbi, Olfa; Sakly, Mohsen; Abdelmelek, Hafedh

    2014-01-01

    The aim of the present study was to investigate the interaction of zinc chloride (3 mg/kg, intraperitoneally [ip]) in rat liver in terms of the biosynthesis of nanoparticles. Zinc treatment increased zinc content in rat liver. Analysis of fluorescence revealed the presence of red fluorescence in the liver following zinc treatment. Interestingly, the co-exposure to zinc (3 mg/kg, ip) and selenium (0.20 mg/L, per os [by mouth]) led to a higher intensity of red fluorescence compared to zinc-treated rats. In addition, X-ray diffraction measurements carried out on liver fractions of zinc-treated rats point to the biosynthesis of zinc sulfide and/or selenide nanocomplexes at nearly 51.60 nm in size. Moreover, co-exposure led to nanocomplexes of about 72.60 nm in size. The interaction of zinc with other mineral elements (S, Se) generates several nanocomplexes, such as ZnS and/or ZnSe. The nanocomplex ZnX could interact directly with enzyme activity or indirectly by the disruption of mineral elements’ bioavailability in cells. Subacute zinc or selenium treatment decreased malondialdehyde levels, indicating a drop in lipid peroxidation. In addition, antioxidant enzyme assays showed that treatment with zinc or co-treatment with zinc and selenium increased the activities of glutathione peroxidase, catalase, and superoxide dismutase. Consequently, zinc complexation with sulfur and/or selenium at nanoscale level could enhance antioxidative responses, which is correlated to the ratio of number of ZnX nanoparticles (X=sulfur or X=selenium) to malondialdehyde level in rat liver. PMID:24403828

  20. Propensity for social interaction predicts nicotine-reinforced behaviors in outbred rats.

    PubMed

    Wang, T; Han, W; Wang, B; Jiang, Q; Solberg-Woods, L C; Palmer, A A; Chen, H

    2014-02-01

    Social and genetic factors can influence smoking behavior. Using olfactogustatory stimuli as the sensory cue for intravenous nicotine self-administration (SA), we previously showed that social learning of nicotine contingent odor cue prevented rats from developing conditioned taste aversion and allowed them to instead establish stable nicotine SA. We hypothesized that genetic factors influenced socially acquired nicotine SA. A heterogeneous stock (HS; N/NIH) of outbred rats was trained to self-administer nicotine using the social learning protocol. Both male and female HS rats acquired nicotine SA, but females self-administered more nicotine than males. After extinction, the context previously paired with nicotine SA, in conjunction with socially transmitted drug cues, was sufficient to cause reinstatement of drug-seeking behavior. Wide variation in both nicotine intake and reinstatement was observed. Using multiple regression analysis, we found that measures of social interaction were significant predictors of nicotine intake and reinstatement of drug seeking in both males and females. Furthermore, measures of depression were predictors of nicotine intake in both males and females, anxiety was a predictor only in males and response to novelty was a predictor only in females. In males, measures of both depression and anxiety predicted nicotine reinstatement. Together, these data supported the ideas that genetically determined propensities for emotional and social phenotypes are significant determinants for nicotine-reinforced behavior, and that the HS rat is a suitable tool for dissecting genetic mechanisms that may underlie the interaction between social behavior, anxiety, depression and smoking. PMID:24289793

  1. [Diagnostics of polycystic ovary syndrome].

    PubMed

    Lazúrová, Ivica; Figurová, Jana; Lazúrová, Zora

    2015-12-01

    Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy among women of reproductive age and the most frequent cause of menstruation cycle disorders. It is marked by a hyperandrogenic state (clinical and/or biochemical) and ovulatory dysfunction (anovulation and/or ultrasonographic finding of polycystic ovaries), which are also criteria for its diagnosis according to Androgen Excess and PCOS Society. The syndrome has multiple phenotypic expressions, among them besides the above characteristics also a metabolic syndrome, primarily obesity and insulin resistance. Diagnosing of PCOS may be rather exacting in clinical practice and it remains to be a diagnosis per exclusionem, following elimination of other causes of hyperandrogenic state and chronic oligo-anovulation. It requires a close cooperation between a gynecologist and endocrinologist and with regard to frequent metabolic complications also with an internist, diabetologist and possibly cardiologist. PMID:27124971

  2. Metabolic Syndrome: Polycystic Ovary Syndrome.

    PubMed

    Mortada, Rami; Williams, Tracy

    2015-08-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous condition characterized by androgen excess, ovulatory dysfunction, and polycystic ovaries. It is the most common endocrinopathy among women of reproductive age, affecting between 6.5% and 8% of women, and is the most common cause of infertility. Insulin resistance is almost always present in women with PCOS, regardless of weight, and they often develop diabetes and metabolic syndrome. The Rotterdam criteria are widely used for diagnosis. These criteria require that patients have at least two of the following conditions: hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. The diagnosis of PCOS also requires exclusion of other potential etiologies of hyperandrogenism and ovulatory dysfunction. The approach to PCOS management differs according to the presenting symptoms and treatment goals, particularly the patient's desire for pregnancy. Weight loss through dietary modifications and exercise is recommended for patients with PCOS who are overweight. Oral contraceptives are the first-line treatment for regulating menstrual cycles and reducing manifestations of hyperandrogenism, such as acne and hirsutism. Clomiphene is the first-line drug for management of anovulatory infertility. Metformin is recommended for metabolic abnormalities such as prediabetes, and a statin should be prescribed for cardioprotection if the patient meets standard criteria for statin therapy. PMID:26280343

  3. Interaction of thiamine deficiency and voluntary alcohol consumption disrupts rat corpus callosum ultrastructure.

    PubMed

    He, Xiaohua; Sullivan, Edith V; Stankovic, Roger K; Harper, Clive G; Pfefferbaum, Adolf

    2007-10-01

    The relative roles of alcohol and thiamine deficiency in causing brain damage remain controversial in alcoholics without the Wernicke-Korsakoff syndrome. Experimental control over alcohol consumption and diet are impossible in humans but can be accomplished in animal models. This experiment was designed to differentiate the separate and combined effects on the macro- and ultrastructure of the corpus callosum of thiamine deficiency and voluntary alcohol consumption. Adult male alcohol-preferring (P) rats (9 chronically alcohol-exposed and 9 water controls) received a thiamine-deficient diet for 2 weeks. There were four groups: five rats previously exposed to alcohol were treated with pyrithiamine (a thiamine phosphorylation inhibitor); five rats never exposed to alcohol were treated with pyrithiamine; four alcohol-exposed rats were treated with thiamine; and four rats never exposed to alcohol were treated with thiamine. On day 14, thiamine was restored in all 18 rats; 2 weeks later the 10 pyrithiamine-treated rats received intraperitoneal thiamine. The rats were perfused 61 days post-pyrithiamine treatment at age 598 days. Brains were dissected and weight and volumes were calculated. Sagittal sections were stained to measure white matter structures. The corpus callosum was examined using transmission electron microscopy to determine density of myelinated fibers, fiber diameter, and myelin thickness. The corpus callosum in the alcohol/pyrithiamine group was significantly thinner, had greater fiber density, higher percentage of small fibers, and myelin thinning than in the alcohol/thiamine and water/thiamine groups. Several measures showed a graded effect, where the alcohol/pyrithiamine group had greater pathology than the water/pyrithiamine group, which had greater pathology than the two thiamine-replete groups. Across all 16 rats, thinner myelin sheaths correlated with higher percentage of small fibers. Myelin thickness and axon diameter together accounted for 71

  4. Expression and interaction of TNF-α and VEGF in chronic stress-induced depressive rats

    PubMed Central

    LI, BAOHUA; WANG, BIN; CHEN, MIN; LI, GONGYING; FANG, MAOSHENG; ZHAI, JINGUO

    2015-01-01

    The incidence of depression increases annually but the pathogenesis is not yet fully understood. The aim of the present study was to explore the expression and interaction of tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) in chronic stress-induced depressive rats. A total of 20 adult healthy Sprague Dawley rats (180–220 g) were randomly divided into the control and experimental depression groups. The depression model was established with a chronic stress method, and the success of model construction was assessed through weigh measurements and the sugar consumption and open-field tests. The expression of TNF-α and VEGF was detected using the reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting and immunohistochemistry. Compared with the control group, the weight of the rats in the experimental group was found to be reduced (P<0.05). The open-field test showed significant differences in the horizontal and vertical motion of the rats between the two groups, and the rats in the experimental group exhibited a significantly reduced ability to adapt to a new environment (P<0.05). Furthermore, the sensitivity of the rats in the experimental group to reward stimulation was decreased. The relative mRNA expression levels of TNF-α and VEGF in the hippocampus of the experimental group were lower than those in the control group, and western blot analysis revealed that the protein expression of VEGF and TNF-α was reduced in the experimental group. Neurons of the experimental group exhibited reduced immunohistochemical staining compared with neurons from the normal hippocampus in the control group. In conclusion, the present study investigated the association between the occurrence of depression and TNF-α and VEGF at the mRNA and protein levels using RT-qPCR, western blotting, immunohistochemistry and animal behavior experiments. The results provide a fundamental basis for follow-up clinical research. PMID

  5. Interactive effects of growth hormone and exercise on muscle mass in suspended rats

    NASA Technical Reports Server (NTRS)

    Grindeland, Richard E.; Roy, Roland R.; Edgerton, V. Reggie; Grossman, Elena J.; Mukku, Venkat R.; Jiang, Bian; Pierotti, David J.; Rudolph, Ingrid

    1994-01-01

    Measures to attenuate muscle atrophy in rats in response to simulated microgravity (hindlimb suspension (HS)) have been only partially successful. In the present study, hypophysectomized rats were in HS for 7 days, and the effects of recombinant human growth hormone (GH), exercise (Ex), or GH+Ex on the weights, protein concentrations, and fiber cross-sectional areas (CSAs) of hindlimb muscles were determined. The weights of four extensor muscles, i.e., the soleus (Sol), medial (MG) and lateral (LG) gastrocnemius, and plantaris (Plt), and one adductor, i.e., the adductor longus (AL), were decreased by 10-22% after HS. Fiber CSAs were decreased by 34% in the Sol and by 1 17% in the MG after HS. In contrast, two flexors, i.e., the tibialis anterior (TA) and extensor digitorum longus (EDL), did not atrophy. In HS rats, GH treatment alone maintained the weights of the fast extensors (MG, LG, Plt) and flexors (TA, EDL) at or above those of control rats. This effect was not observed in the slow extensor (Sol) or AL. Exercise had no significant effect on the weight of any muscle in HS rats. A combination of GH and Ex treatments yielded a significant increase in the weights of the fast extensors and in the CSA of both fast and slow fibers of the MG and significantly increased Sol weight and CSA of the slow fibers of the Sol. The AL was not responsive to either GH or Ex treatments. Protein concentrations of the Sol and MG were higher only in the Sol of Ex and GH+Ex rats. These results suggest that while GH treatment or intermittent high intensity exercise alone have a minimal effect in maintaining the mass of unloaded muscle, there is a strong interactive effect of these two treatments.

  6. Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats.

    PubMed

    Briggs, Scott A; Hall, Brandon J; Wells, Corinne; Slade, Susan; Jaskowski, Paul; Morrison, Margaret; Rezvani, Amir H; Rose, Jed E; Levin, Edward D

    2016-03-01

    Combining effective treatments with diverse mechanisms of action for smoking cessation may provide better therapy by targeting multiple points of control in the neural circuits underlying addiction. Previous research in a rat model has shown that dextromethorphan, which has α3β4 nicotinic and NMDA glutamatergic antagonist actions, significantly decreases nicotine self-administration. We have found in the rat model that the H1 histamine antagonist pyrilamine and the serotonin 5HT2C agonist lorcaserin also significantly reduce nicotine self-administration. The current studies were conducted to determine the interactive effects of dextromethorphan with pyrilamine and lorcaserin on nicotine self-administration in rats. Young adult female rats were fitted with jugular IV catheters and trained to self-administer a nicotine infusion dose of 0.03-mg/kg/infusion. In an initial dose-effect function study of dextromethorphan, we found a monotonic decrease in nicotine self-administration over a dose range of 1 to 30-mg/kg with the lowest effective dose of 3-mg/kg. Then, with two separate cohorts of rats, dextromethorphan (0, 3.3, and 10-mg/kg) interactions with pyrilamine (0, 4.43, and 13.3-mg/kg) were investigated as well as interactions with lorcaserin (0, 0.3125 and 0.625-mg/kg). In the pyrilamine-dextromethorphan interaction study, an acute dose of pyrilamine (13.3-mg/kg) as well as an acute dose of dextromethorphan caused a significant decrease in nicotine self-administration. There were mutually augmenting effects of these two drugs. The combination of dextromethorphan (10-mg/kg) and pyrilamine (13.3-mg/kg) significantly lowered nicotine self-administration relative to either 10-mg/kg of dextromethorphan alone (p<0.05) or 13.3-mg/kg of pyrilamine alone (p<0.0005). In the lorcaserin-dextromethorphan study, an acute dose of lorcaserin (0.312-mg/kg) as well as an acute dose of dextromethorphan (10-mg/kg) caused a significant decrease in nicotine self

  7. Chronic exposures to low levels of estradiol and their effects on the ovaries and reproductive hormones: Comparison with aging

    PubMed Central

    Gilbreath, Ebony T.; MohanKumar, Sheba M.J.; Balasubramanian, Priya; Agnew, Dalen W.; MohanKumar, P.S.

    2015-01-01

    Aging in female rats is characterized by a state called “constant estrous” in which rats are unable to ovulate, have polycystic ovaries and moderately elevated estrogen levels. We hypothesized that chronic exposure of young animals to low levels of E2 can produce reproductive changes similar to that seen in aging animals. Adult female rats were sham-implanted (control) or implanted with slow-release E2 (20 ng/day) pellets for 30, 60, or 90 days. Old constant estrous (OCE) rats were used for comparison. Estrous cyclicity was monitored periodically. At the end of treatment, animals were sacrificed, trunk blood was collected for hormone measurements and ovaries for immunohistochemistry. Young animals became acyclic with increasing duration of E2 exposure while OCE rats were in a state of acyclicity. Ovaries became increasingly more cystic with E2 exposure, and were comparable to OCE rats; however, there was a marked reduction in interstitial tissue with exogenous E2 treatment. Exogenous E2 also decreased Mullerian inhibiting substance expression, increased infiltration of macrophages without much impact on apoptosis in the ovaries. Serum testosterone levels decreased in E2-treated young animals, while it increased significantly in OCE rats. There was a marked reduction in LH but not FSH levels with E2 exposure in both young and old animals. These results indicate that even very low doses of E2 are capable of inducing aging-like changes in young animals. PMID:26779558

  8. Changes in the sexual behavior and testosterone levels of male rats in response to daily interactions with estrus females

    PubMed Central

    Shulman, Leanne M.; Spritzer, Mark D.

    2014-01-01

    Male rat sexual behavior has been intensively studied over the past 100 years, but few studies have examined how sexual behavior changes over the course of several days of interactions. In this experiment, adult male rats (n = 12) were given daily access to estrus females for 30 min per day for 15 consecutive days and control males did not interact with females. Ovariectomized females were induced into estrus with hormonal injections, and males interacted with a different female each day. The amount of sexual activity (mounts, intromissions, and ejaculations) was found to cycle with a period of approximately 4 days in most male rats. Additionally, blood was collected every other day following sexual interactions to assess serum testosterone levels. Testosterone was found to peak on the first day of interaction and then fell back to near the level of control rats that did not interact with females. Following the initial peak, testosterone concentrations fluctuated less in males exposed to females than in controls. Sexual activity was not found to predict testosterone concentration. We conclude that when male rats have daily sexual interactions, sexual behavior tends to show cyclic changes and testosterone is significantly elevated only on the first day of interactions. PMID:24813700

  9. Changes in the sexual behavior and testosterone levels of male rats in response to daily interactions with estrus females.

    PubMed

    Shulman, Leanne M; Spritzer, Mark D

    2014-06-22

    Male rat sexual behavior has been intensively studied over the past 100 years, but few studies have examined how sexual behavior changes over the course of several days of interactions. In this experiment, adult male rats in the experimental group (n=12) were given daily access to estrus females for 30 min per day for 15 consecutive days while control males (n=11) did not interact with females. Ovariectomized females were induced into estrus with hormonal injections, and males interacted with a different female each day. The amount of sexual activity (mounts, intromissions, and ejaculations) was found to cycle with a period of approximately 4 days in most male rats. Additionally, blood was collected every other day following sexual interactions to assess serum testosterone levels. Testosterone was found to peak on the first day of interaction and then fell back to near the level of control rats that did not interact with females. Following the initial peak, testosterone concentrations fluctuated less in males exposed to females than in controls. Sexual activity was not found to predict testosterone concentration. We conclude that when male rats have daily sexual interactions, sexual behavior tends to show cyclic changes and testosterone is significantly elevated only on the first day of interactions. PMID:24813700

  10. Effect of alcohol and kolanut interaction on brain sodium pump activity in Wistar albino rats.

    PubMed

    Obochi, G O; Abara, A E; Malu, S P; Obi-Abang, M; Edu, F E; Eteng, M U; Umoh, I B

    2007-01-01

    Effect of alcohol-kolanut interaction on sodium pump activity in wistar albino rats was studied. Thirty wistar albino rats were divided into six groups of five (5) rats per group and used for the study. The control group (1) received via oral route a placebo (4 ml of distilled water). Groups 2 to 6 were treated for a period of 21 days, with (10% v/v) of alcohol (group 2), 50mg/kg body weight of kolanut (group 3), 50 mg/kg body weight of caffeine (group 4), 4 ml of 10% v/v of alcohol and 50 mg/kg body weight kolanut (group 5), 4 ml of 10% v/v of alcohol and 50 mg/kg body weight of caffeine in 4.0 ml of the vehicle via gastric intubation respectively. A day after the final exposure, the brain of each rat was harvested and processed to examine several biochemical parameters, i.e., total ATpase, ouabain-insensitive ATpase, ouabain sensitive ATpase (Na(+)-K(+)ATPase), non-enzymatic breakdown of ATP and inorganic phosphate (Pi) released. The results showed that the essential enzyme of the brain responsible for neuronal function, Na(+)-K(+)ATPase, was inhibited by alcohol-kolanut co-administration relative to control, resulting in a decrease in Na(+)-K(+)ATPase activity, ATP production, ion transport and action potential, leading to loss of neuronal activities. PMID:18379627

  11. Effects of Metabolic Cage Housing on Rat Behavior and Performance in the Social Interaction Test.

    PubMed

    Whittaker, Alexandra L; Lymn, Kerry A; Howarth, Gordon S

    2016-01-01

    Although the metabolic cage is commonly used for housing nonhuman animals in the laboratory, it has been recognized as constituting a unique stressor. Such an environment would be expected to affect behavioral change in animals housed therein. However, few studies have specifically addressed the nature or magnitude of this change. The current study sought to characterize the behavioral time budget of rats in metabolic cage housing in comparison to that of individually housed animals in standard open-top cages. Rats in metabolic cages spent less time moving, manipulating enrichment, and carrying out rearing behaviors, and there was a corresponding shift toward inactivity. In an applied Social Interaction Test, behavioral scoring implied that metabolic cage housing had an anxiogenic effect. In conclusion, metabolic cage housing produces measurable effects on spontaneous and evoked behavior in rats in the laboratory. These behavioral changes may lead to a negative emotional state in these animals, which could have negative welfare consequences. Further research is needed to quantify the existence and magnitude of such an effect on rat well being. PMID:27057787

  12. Interaction between vitamin E and glutathione in rat brain: Effect of chronic ethanol administration.

    PubMed

    Marcus, S R; Chandrakala, M V; Nadiger, H A

    1998-12-01

    The protection against ethanol-induced lipid peroxidation is rendered by antioxidants such as vitamin E and glutathione (GSH) interacting with each other and also functioning independently. A study of the levels of GSH and activities of glutathione peroxidase (GP), glutathione reductase (GR) and glutathione transferase (GST) in the cerebral cortex (CC), cerebellum (CB) and brain stem (BS) of vitamin E-supplemented and -deficient rats subjected to ethanol administration for 30 days was carried out. Chronic ethanol administration to vitamin E-supplemented rats elevated GP, GR and GST activities in the three regions and GSH levels in the CB. Chronic ethanol administration to vitamin E-deficient rats elevated GR activity in the three regions and GP activity in the CC and CB, decreased GST activity in the CC and CB, but did not alter GSH levels compared with normal rats subjected to chronic ethanol administration. The results indicate that vitamin E helps to maintain GSH levels to combat increased peroxidation while its absence has a deleterious effect. PMID:24393672

  13. Herb-drug interaction of Epimedium extract on the pharmacokinetic of dapoxetine in rats.

    PubMed

    Hsueh, Thomas Y; Ho, Jing-Kai; Lin, Lie-Chwen; Chiu, Allen W; Lin, Chi-Hung; Tsai, Tung-Hu

    2016-03-01

    The aim of study is to develop a high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method to investigate the pharmacokinetic interaction of Epimedium extract on the dapoxetine in rats. Experimental rats were divided into the following four parallel groups: (1) dapoxetine alone (10mg/kg, i.v.); (2) oral administration of Epimedium extract (2g/kg) for 3 consecutive days and on the fourth day dapoxetine was administered (10mg/kg, i.v.); (3) dapoxetine alone (10mg/kg, p.o.); (4) oral administration of Epimedium extract (2g/kg) for 3 consecutive days and on the fourth day dapoxetine was administered (10mg/kg, p.o.). The calibration curves of dapoxetine were acquired over a concentration ranges from 1 to 500ng/mL with the R(2)=0.999. The mean matrix effects and extraction recoveries of dapoxetine at three different concentrations (1, 10, 500ng/mL) ranged from 107.3 to 110.9% and from 25.5 to 28.2% respectively. The interday and intraday relative standard deviation were both <6% while the bias were both <14%. The pharmacokinetic results demonstrated that pretreated with/without Epimedium extract for three consecutive days did not significant alter the pharmacokinetics of dapoxetine in rats. The oral bioavailability of dapoxetine was about 75% in rats. PMID:26874879

  14. Polycystic ovary syndrome in the Indian Subcontinent.

    PubMed

    Allahbadia, Gautam N; Merchant, Rubina

    2008-01-01

    Polycystic ovary syndrome (PCOS) is a complex, multifaceted, heterogeneous disorder that affects approximately 5 to 10% of women of reproductive age. It is characterized by hyperandrogenism, polycystic ovaries, and chronic anovulation along with insulin resistance, hyperinsulinemia, abdominal obesity, hypertension, and dyslipidemia as frequent metabolic traits (metabolic syndrome) that culminate in serious long-term consequences such as type 2 diabetes mellitus, endometrial hyperplasia, and coronary artery disease. It is one of the most common causes of anovulatory infertility. However, the heterogeneous clinical features of PCOS may change throughout the life span, starting from adolescence to postmenopausal age, largely influenced by obesity and metabolic alterations, and the phenotype of women with PCOS is variable, depending on the ethnic background. The etiology of PCOS is yet to be elucidated; however, it is believed that in utero fetal programming may have a significant role in the development of PCOS phenotype in adult life. Though a woman may be genetically predisposed to developing PCOS, it is only the interaction of environmental factors (obesity) with the genetic factors that results in the characteristic metabolic and menstrual disturbances and the final expression of the PCOS phenotype. Irrespective of geographic locations, a rapidly increasing prevalence of polycystic ovarian insulin resistance syndrome, excess body fat, adverse body fat patterning, hypertriglyceridemia, and obesity-related disease, such as diabetes and cardiovascular disease, have been reported in Asian Indians, suggesting that primary prevention strategies should be initiated early in this ethnic group. In lieu of the epidemic increase in the prevalence of obesity and diabetes mellitus in most industrialized countries including China and India owing to Westernization, urbanization, and mechanization, and evidence suggesting a pathogenetic role of obesity in the development of PCOS

  15. Pharmacological characterisation of a modified social interaction model of anxiety in the rat.

    PubMed

    Guy, A P; Gardner, C R

    1985-01-01

    Social interaction (SI) between two unfamiliar male rats in a dimly lit, familiar environment has been investigated as a model of anxiety, where novelty of the partner remains as the principal anxiogenic stimulus. A range of centrally acting drugs have been tested in this situation. Chlordiazepoxide, nitrazepam, flunitrazepam, and flurazepam all increase SI, as does buspirone, CL 218872, suriclone, sodium valproate, and nicotinamide in the model described. Anxiogenic agents FG 7142 and yohimbine reduced SI without significant modification of motor activities. However, the stimulant amphetamine increased all behaviours in this condition. Amphetamine also increased all behaviours when rats were tested with their cagemates, when the desire for SI is largely satiated. CL 218872 also increased SI in this second situation, and it is suggested that this agent may have a non-specific component in its action in this test. Additionally, caffeine, theophylline, and piracetam may also have non-specific behavioural actions in this model. PMID:2864655

  16. Polycystic Ovary Syndrome in Adolescents.

    PubMed

    Witchel, Selma Feldman; Roumimper, Hailey; Oberfield, Sharon

    2016-06-01

    Polycystic ovary syndrome (PCOS) is a familial heterogeneous disorder affecting 6% to 10% of reproductive-age women. The use of criteria developed for adult women is problematic for the adolescent girl because the clinical features associated with PCOS are normal pubertal events. The recent consensus statement on PCOS in adolescents stated that hyperandrogenism and oligomenorrhea need to persist for at least 2 years to consider the diagnosis of PCOS. Although insulin resistance, hyperinsulinism, and obesity are often associated with PCOS, these features are not considered valid diagnostic criteria. Recent genomewide association studies implicate genetic loci involved in the hypothalamic-pituitary-ovarian axis. PMID:27241968

  17. Negligible Pharmacokinetic Interaction of Red Ginseng and Losartan, an Antihypertensive Agent, in Sprague-Dawley Rats.

    PubMed

    Ryu, Sung Ha; Kim, Yong Soon; Jang, Hyun-Jun; Kim, Kyu-Bong

    2015-01-01

    Red ginseng (RG) is one of the top selling herbal medicines in Korea, but is not recommended in hypertensive patients. In this study, the pharmacokinetic (PK) interaction between RG and losartan, an antihypertensive drug, was examined. RG was orally administered for 2 wk to male Sprague-Dawley (S-D) rats at either control (0), 0.5, 1, or 2 g/kg/d for 2 wk. After the last administration of RG and 30 min later, all animals were treated with 10 mg/kg losartan by oral route. In addition, some S-D rats were administered RG orally for 21 d at 2 g/kg followed by losartan intravenously (iv) at 10 mg/kg/d. Post losartan administration, plasma samples were collected at 5, 15, and 30 min and 1, 1.5, 2, 3, 6, 12, and 24 h. Plasma concentrations of losartan and E-3174, the active metabolite of losartan, were analyzed by a high-pressure liquid chromatography-tandem mass spectrometer system (LC-MS/MS). Oral losartan administration showed dose-dependent pharmacokinetics (PK) increase with time to maximum plasma, but this was not significant between different groups. There was no significant change in tmax with E-3174 PK. With iv losartan, pharmacokinetics showed elevation of area under the plasma concentration-time curve from time zero extrapolated to infinitity. There was not a significant change in AUCinf with E-3174 PK. Therefore, RG appeared to interfere with biotransformation of losartan, as RG exerted no marked effect on E-3174 PK in S-D rats. Data demonstrated that oral or iv treatment with losartan in rats pretreated with RG for 2 wk showed that losartan PK was affected but E-3174 PK remained unchanged among different dose groups. These results suggested that RG induces negligible influence on losartan and E-3174 PK in rats. PMID:26514876

  18. The interaction between working and reference spatial memories in rats on a radial maze.

    PubMed

    Guitar, Nicole A; Roberts, William A

    2015-03-01

    The interaction of reference and working memory was studied in rats on an eight-arm radial maze. Each trial involved a two-phase procedure in which a rat was forced to enter four arms on the maze in a study phase and then was allowed to choose among all eight arms in a test phase given 5-s later, with choice of only the previously unvisited arms rewarded. For each rat, two arms on the maze were designated as reference memory arms because they were never entered in the study phase and were always rewarded in the test phase. The other two arms never entered in the study phase and rewarded in the test phase were working memory arms and varied randomly from trial to trial. In Experiment 1, rats showed acquisition of equivalent preference for entering the reference and working memory arms in their first four choices of the test phase. Subsequent tests carried out in Experiment 2 compared performance at 5-s, 1-h, and 24-h retention intervals when reference memory and working memory were congruent and incongruent. Higher accuracy for choice of reference memory arms than working memory arms appeared at the 1-h and 24-h retention intervals on congruent tests but not on incongruent tests. A process dissociation procedure analysis indicated that working memory but not reference memory declined over the 24-h retention interval. The interaction of working and reference memory was shown by superior choice of reference memory arms on congruent tests than on incongruent tests at 1-h and 24-h retention intervals but not at the 5-s retention interval. These findings suggest that working and reference memory are independent systems that can facilitate and compete with one another. This article is part of a Special Issue entitled: Tribute to Tom Zentall. PMID:25452076

  19. Folliculostellate cell interacts with pericyte via TGFβ2 in rat anterior pituitary.

    PubMed

    Tsukada, Takehiro; Azuma, Morio; Horiguchi, Kotaro; Fujiwara, Ken; Kouki, Tom; Kikuchi, Motoshi; Yashiro, Takashi

    2016-05-01

    The anterior pituitary gland comprises five types of endocrine cells plus non-endocrine cells including folliculostellate cells, endothelial cells, and capillary mural cells (pericytes). In addition to being controlled by the hypothalamic-pituitary-target organ axis, the functions of these cells are likely regulated by local cell and extracellular matrix (ECM) interactions. However, these complex interactions are not fully understood. We investigated folliculostellate cell-mediated cell-to-cell interaction. Using S100β-GFP transgenic rats, which express GFP in folliculostellate cells, we designed a three-dimensional cell culture to examine the effects of folliculostellate cells. Interestingly, removal of folliculostellate cells reduced collagen synthesis (Col1a1 and Col3a1). Because pericytes are important collagen-producing cells in the gland, we stained for desmin (a pericyte marker). Removal of folliculostellate cells resulted in fewer desmin-positive pericytes and less desmin mRNA. We then attempted to identify the factor mediating folliculostellate cell-pericyte interaction. RT-PCR and in situ hybridization revealed that the important profibrotic factor transforming growth factor beta-2 (TGFβ2) was specifically expressed in folliculostellate cells and that TGFβ receptor II was expressed in pericytes, endothelial cells, and parenchymal cells. Immunocytochemistry showed that TGFβ2 induced SMAD2 nuclear translocation in pericytes. TGFβ2 increased collagen synthesis in a dose-dependent manner. This action was completely blocked by TGFβ receptor I inhibitor (SB431542). Diminished collagen synthesis in folliculostellate cell-deficient cell aggregates was partially recovered by TGFβ2. TGFβ2-mediated folliculostellate cell-pericyte interaction appears to be essential for collagen synthesis in rat anterior pituitary. This finding sheds new light on local cell-ECM interactions in the gland. PMID:26957638

  20. Spinal antinociceptive action of amiloride and its interaction with tizanidine in the rat formalin test

    PubMed Central

    Ouyang, Handong; Wang, Peizong; Huang, Wan; Li, Qiang; Nie, Bilin; Zeng, Weian

    2015-01-01

    BACKGROUND: Amiloride has been reported to produce a wide variety of actions, thereby affecting several ionic channels and a multitude of receptors and enzymes. Intrathecal α2-adrenergic receptor agonists produce pronounced analgesia, and amiloride modulates α2-adrenergic receptor agonist binding and function, acting via the allosteric site on the α2A-adrenergic receptor. OBJECTIVES: To investigate the antinociceptive interaction of intrathecal amiloride and the α2-adrenoceptor agonist tizanidine using a rat formalin test. METHODS: Sprague-Dawley rats were chronically implanted with lumbar intrathecal catheters and were tested for paw flinching using formalin injection. Biphasic painful behaviour was recorded. Amiloride, tizanidine or an amiloride-tizanidine mixture was administered 10 min before formalin injection. To characterize any interactions, isobolographic analysis was performed. The effects of a pretreatment using intrathecally administered yohimbine was also tested. RESULTS: Intrathecally administered amiloride (12.5 μg to 100 μg) and tizanidine (0.5 μg to 5 μg), given separately, produced a significant dose-related suppression of the biphasic responses in the formalin test. Isobolographic analysis revealed that the combination of intrathecal amiloride and tizanidine synergistically reduced phase I and II activities. Intrathecally administered yohimbine antagonized or attenuated the antinociceptive effect of amiloride, tizanidine and the amiloride-tizanidine mixture. Intrathecally administered amiloride synergistically interacts with tizanidine to reduce the nociceptive response in the formalin test, most likely by activating α2-adrenoceptors in the spinal cord. CONCLUSIONS: Although intrathecal tizanidine produced pronounced analgesia, antinociceptive doses of intrathecal tizanidine also produced several side effects, including bradycardia and sedation. Amiloride produced antinociceptive action against the thermal nociceptive test without side

  1. Interactive effects of nutrition, environment, and rat-strain on cortical and vertebral bone geometry and biomechanics

    NASA Technical Reports Server (NTRS)

    Zernicke, R. F.; Li, K.-C.; Salem, G. J.; Vailas, A. C.; Grindeland, R. E.

    1990-01-01

    An investigation was conducted to generate comparative data on the sensitivity of cortical- and vertebral-bone adaptations in two different rat strains maintained at conditions typical for spaceborne experiments conducted by U.S.A. and USSR. The effects of cage environment, diet, and rat-strain on the cortical (humerus) and vertebral (T7) bones of male Taconic-Sprague-Dawley and Czechoslovakian-Wistar rats were investigated using different flight-simulation cages (one rat/cage for U.S.A.; ten rats/cage for USSR conditions) and fed either U.S.A. or USSR diet. The results showed significant effects of these factors on the humeral and vertebral geometry and mechanical properties, as well as significant interactive effects on the mechanical properties of the humerus.

  2. Immunological Interactive Effects between Pollen Grains and Their Cytoplasmic Granules on Brown Norway Rats

    PubMed Central

    2009-01-01

    Background Grass pollen is one of the most important aeroallergen vectors in Europe. Under some meteorological factors, pollen grains can release pollen cytoplasmic granules (PCGs). PCGs induce allergic responses. Several studies have shown that during a period of thunderstorms the number of patients with asthma increases because of higher airborne concentrations of PCGs. Objective The aims of the study were to assess the allergenicity of interactive effects between pollen and PCGs and to compare it with allergenicity of Timothy grass pollen and PCGs in Brown Norway rats. Methods Rats were sensitized (day 0) and challenged (day 21) with pollen grains and/or PCGs. Four groups were studied: pollen-pollen (PP), PCGs-PCGs (GG), pollen-PCGs (PG), and PCGs-pollen (GP). Blood samples, bronchoalveolar lavage fluid, and bronchial lymph node were collected at day 25. IgE and IgG1 levels in sera were assessed by enzyme-linked immunosorbent assay. Alveolar cells, protein, and cytokine concentrations were quantified in bronchoalveolar lavage fluid. T-cell proliferation, in response to pollen or granules, was performed by lymph node assay. Results Interactive effects between pollen and PCGs increased IgE and IgG1 levels when compared with those of the negative control. These increases were lower than those of the PP group but similar to the levels obtained by the GG group. Whatever was used in the sensitization and/or challenge phase, PCGs increased lymphocyte and Rantes levels compared with those of the pollen group. The interactive effects increased IL-1α and IL-1β compared with those of the PP and GG groups. Conclusions Immunologic interactive effects have been shown between pollen and PCGs. For humoral and cellular allergic responses, interactive effects between the 2 aeroallergenic sources used in this study seem to be influenced mainly by PCGs. PMID:23283149

  3. Obesity and polycystic ovary syndrome.

    PubMed

    Naderpoor, N; Shorakae, S; Joham, A; Boyle, J; De Courten, B; Teede, H J

    2015-03-01

    Obesity is now a major international health concern. It is increasingly common in young women with reproductive, metabolic and psychological health impacts. Reproductive health impacts are often poorly appreciated and include polycystic ovary syndrome (PCOS), infertility and pregnancy complications. PCOS is the most common endocrine condition in women and is underpinned by hormonal disturbances including insulin resistance and hyperandrogenism. Obesity exacerbates hormonal and clinical features of PCOS and women with PCOS appear at higher risk of obesity, with multiple underlying mechanisms linking the conditions. Lifestyle intervention is first line in management of PCOS to both prevent weight gain and induce weight loss; however improved engagement and sustainability remain challenges with the need for more research. Medications like metformin, orlistat, GLP1 agonists and bariatric surgery have been used with the need for large scale randomised clinical trials to define their roles. PMID:25411807

  4. Lack of interaction between dietary fructose and zinc (Zn) nutriture in rats

    SciTech Connect

    Smith, J.C.; Failla, M.L.; Fields, M.; Revett, K.R.; Rose, A.

    1986-03-05

    Dietary fructose, when compared to cornstarch, exacerbates copper deficiency. The purpose of this study was to determine whether Zn deficiency is similarly enhanced by high fructose intake. Seventy-five male SD rats were randomly assigned to one of the following diets containing 62% of the indicated carbohydrate: Zn deficient (0.6 ppm) X fructose; Zn deficient X starch; Zn supplemented (32 ppm) X fructose; Zn supplemented X starch. Animals were pair-fed to the Zn deficient X fructose group for 4 weeks. Survival, weight gain and tissue weight were also affected by dietary Zn, but not dietary carbohydrate. Dietary carbohydrate also failed to alter food intake of rats consuming Zn deficient diets. Unlike copper deficiency, the severity of Zn deficiency is not increased by feeding diets high in fructose compared to starch. The lack of a carbohydrate effect on zinc status indicates that the fructose-copper interaction is selective. This knowledge will facilitate the design of studies aimed at defining the mechanism(s) underlying fructose-trace element interaction.

  5. Interaction of IFN-γ with Cholinergic Agonists to Modulate Rat and Human Goblet Cell Function

    PubMed Central

    García-Posadas, L; Hodges, RR; Li, D; Shatos, MA; Storr-Paulsen, T; Diebold, Y; Dartt, DA

    2015-01-01

    Goblet cells populate wet-surfaced mucosa including the conjunctiva of the eye, intestine, and nose, among others. These cells function as part of the innate immune system by secreting high molecular weight mucins that interact with environmental constituents including pathogens, allergens, and particulate pollutants. Herein we determined whether IFN-γ, a Th1 cytokine increased in dry eye, alters goblet cell function. Goblet cells from rat and human conjunctiva were cultured. Changes in intracellular [Ca2+] ([Ca2+]i), high molecular weight glycoconjugate secretion, and proliferation were measured after stimulation with IFN-γ with or without the cholinergic agonist carbachol. IFN-γ itself increased [Ca2+]i in rat and human goblet cells and prevented the increase in [Ca2+]i caused by carbachol. Carbachol prevented IFN-γ-mediated increase in [Ca2+]i. This cross-talk between IFN-γ and muscarinic receptors may be partially due to use of the same Ca2+i reservoirs, but also from interaction of signaling pathways proximal to the increase in [Ca2+]i. IFN-γ blocked carbachol-induced high molecular weight glycoconjugate secretion and reduced goblet cell proliferation. We conclude that increased levels of IFN-γ in dry eye disease could explain the lack of goblet cells and mucin deficiency typically found in this pathology. IFN-γ could also function similarly in respiratory and gastrointestinal tracts. PMID:26129651

  6. Synergistic effect of the interaction between curcumin and diclofenac on the formalin test in rats.

    PubMed

    De Paz-Campos, Marco A; Ortiz, Mario I; Chávez Piña, Aracely E; Zazueta-Beltrán, Liliana; Castañeda-Hernández, Gilberto

    2014-10-15

    The association of non-steroidal anti-inflammatory drugs with certain plant extracts can increase antinociceptive activity, permitting the use of lower doses and thus limiting side effects. Therefore, the aim objective of the current study was to examine the effects of curcumin on the nociception and pharmacokinetics of diclofenac in rats. Antinociception was assessed using the formalin test. Diluted formalin was injected subcutaneously into the dorsal surface of the right hind paw. Nociceptive behavior was quantified as the number of flinches of the injected paw during 60 min after injection, and a reduction in formalin-induced flinching was interpreted as an antinociceptive response. Rats were treated with oral diclofenac (1-31 mg/kg), curcumin (3.1-100 mg/kg) or the diclofenac-curcumin combination (2.4-38.4 mg/kg). To determine the possibility of a pharmacokinetic interaction, the oral bioavailability of diclofenac (10 mg/kg) was studied in presence and the absence of curcumin (31 mg/kg). Diclofenac, curcumin, or diclofenac-curcumin combination produced an antinociceptive effect on the formalin test. ED30 values were estimated for the individual drugs, and an isobologram was constructed. The derived theoretical ED30 for the antinociceptive effect (19.2 mg/kg) was significantly different from the observed experimental ED30 value (9.8 mg/kg); hence, the interaction between diclofenac and curcumin that mediates the antinociceptive effect was synergistic. Notwithstanding, the interaction does not appear to involve pharmacokinetic mechanisms, as oral curcumin failed to produce any significant alteration in oral diclofenac bioavailability. Data suggest that the diclofenac-curcumin combination can interact at the systemic level and may have therapeutic advantages for the clinical treatment of inflammatory pain. PMID:25442263

  7. Laparoscopic management of tumor in supernumerary ovary

    PubMed Central

    Prakash, Ved; Kant, Anita; Parashar, Abha; Rani, Uma

    2016-01-01

    Laparoscopic management of most of the adnexal masses has become feasible in the present era of advancing endoscopic techniques. A postmenopausal lady presented with lump in the abdomen, appeared to be a solid ovarian mass on ultrasound, and magnetic resonance imaging. On laparoscopy, both the ovaries were normal and the mass was not connected to uterus or adnexa. The mass was removed and histopathology confirmed it to be ovarian tissue thus confirming it to be a tumor in a supernumerary ovary. Examples of supernumerary ovary are among the rarest of gynecological abnormalities. PMID:27134478

  8. Laparoscopic management of tumor in supernumerary ovary.

    PubMed

    Prakash, Ved; Kant, Anita; Parashar, Abha; Rani, Uma

    2016-01-01

    Laparoscopic management of most of the adnexal masses has become feasible in the present era of advancing endoscopic techniques. A postmenopausal lady presented with lump in the abdomen, appeared to be a solid ovarian mass on ultrasound, and magnetic resonance imaging. On laparoscopy, both the ovaries were normal and the mass was not connected to uterus or adnexa. The mass was removed and histopathology confirmed it to be ovarian tissue thus confirming it to be a tumor in a supernumerary ovary. Examples of supernumerary ovary are among the rarest of gynecological abnormalities. PMID:27134478

  9. Interaction of rat Sertoli cells with a collagen lattice in vitro.

    PubMed

    Borland, K; Ehrlich, H P; Muffly, K; Dills, W L; Hall, P F

    1986-11-01

    Sertoli cells from rats aged 15, 20, and 25 d were subcultured onto collagen-coated, plastic dishes. If the collagen was released from the plastic surface by rimming, the floating rafts of collagen showed uniform shrinkage. If the collagen was allowed to remain attached to the plastic, holes appeared in the collagen with cells from rats aged 25 d but not with those of 15 d. Cells from rats aged 20 d caused fewer and smaller holes to appear. The holes were associated with the formation of clumps of spherical cells from which elongated Sertoli cells extended into the surrounding collagen to end near holes. Rhodamine-phalloidin revealed diffusely distributed actin in the spherical cells in contrast to well-developed microfilaments in the peripheral elongated cells. Addition of cytochalasin B (5 micrograms/ml) to the medium prevented contraction of the floating rafts and the development of holes in the attached collagen. In addition, cytochalasin B caused the peripheral cells to become spherical and to separate from the clumps. Moreover, rhodamine-phalloidin revealed that actin in the peripheral cells occurred as clumps without microfilaments when cytochalasin B was present. When Sertoli cells were subcultured onto silicone rubber films, the cells produced wrinkling of the rubber surface within 4 h of plating. These observations were interpreted to mean that Sertoli cells exert local tractional forces on various substrata. These forces require actin, presumably acting by a contractile mechanism. When the collagen is attached to plastic and the cells are organized into clumps with radiating elongated cells (cells from rats aged 25 d), the tractional forces in the elongated cells reorganize the collagen fibers to produce holes. When cells are uniformly distributed (cells from rats aged 15 d), holes are not formed. When the collagen is released from the plastic surface, tractional forces cause the floating rafts to shrink. These interactions of the cells with collagen are

  10. Asymmetric Multisensory Interactions of Visual and Somatosensory Responses in a Region of the Rat Parietal Cortex

    PubMed Central

    Lippert, Michael T.; Takagaki, Kentaroh

    2013-01-01

    Perception greatly benefits from integrating multiple sensory cues into a unified percept. To study the neural mechanisms of sensory integration, model systems are required that allow the simultaneous assessment of activity and the use of techniques to affect individual neural processes in behaving animals. While rodents qualify for these requirements, little is known about multisensory integration and areas involved for this purpose in the rodent. Using optical imaging combined with laminar electrophysiological recordings, the rat parietal cortex was identified as an area where visual and somatosensory inputs converge and interact. Our results reveal similar response patterns to visual and somatosensory stimuli at the level of current source density (CSD) responses and multi-unit responses within a strip in parietal cortex. Surprisingly, a selective asymmetry was observed in multisensory interactions: when the somatosensory response preceded the visual response, supra-linear summation of CSD was observed, but the reverse stimulus order resulted in sub-linear effects in the CSD. This asymmetry was not present in multi-unit activity however, which showed consistently sub-linear interactions. These interactions were restricted to a specific temporal window, and pharmacological tests revealed significant local intra-cortical contributions to this phenomenon. Our results highlight the rodent parietal cortex as a system to model the neural underpinnings of multisensory processing in behaving animals and at the cellular level. PMID:23667650

  11. Post-hatching development of Alligator mississippiensis ovary and testis

    PubMed Central

    Moore, Brandon C.; Hamlin, Heather J.; Botteri, Nicole L.; Lawler, Ashley N.; Mathavan, Ketan K.; Guillette, Louis J.

    2009-01-01

    We investigated ovary and testis development of Alligator mississippiensis during the first five months post-hatch. To better describe follicle assembly and seminiferous cord development, we employed histochemical techniques to detect carbohydrate-rich extracellular matrix components in one-week, one-month, three-month, and five-month-old gonads. We found profound morphological changes in both ovary and testis. During this time, oogenesis progressed up to diplotene arrest and meiotic germ cells increasingly interacted with follicular cells. Concomitant with follicles becoming invested with full complements of granulosa cells, a periodic acid Schiff’s (PAS)-positive basement membrane formed. As follicles enlarged and thecal layers were observed, basement membranes and thecal compartments gained periodic acid-methionine silver (PAMS)-reactive fibers. The ovarian medulla increased first PAS- and then PAMS-reactivity as it fragmented into wide lacunae lined with low cuboidal to squamous epithelia. During this same period, testicular germ cells found along the tubule margins were observed progressing from spermatogonia to round spermatids located within the center of tubules. Accompanying this meiotic development, interstitial Leydig cell clusters become more visible and testicular capsules thickened. During the observed testis development, the thickening tunica albuginea and widening interstitial tissues showed increasing PAS- and PAMS-reactivity. We observed putative inter-sex structures in both ovary and testis. On the coelomic aspect of testes were cell clusters with germ cell morphology and at the posterior end of ovaries, we observed “medullary rests” resembling immature testis cords. We hypothesize laboratory conditions accelerated gonad maturation due to optimum conditions, including nutrients and temperature. Laboratory alligators grew more rapidly and with increased body conditions compared to previous measured, field-caught animals. Additionally, we

  12. Absorptive interactions of concurrent oral administration of (+)-catechin and puerarin in rats and the underlying mechanisms

    PubMed Central

    Su, Hui-fang; Lin, Qing; Wang, Xin-yi; Fu, Yao; Gong, Tao; Sun, Xun; Zhang, Zhi-rong

    2016-01-01

    Aim: (+)-Catechin and puerarin are polyphenol and flavonoid, respectively, in green tea and foodstuffs. They exhibit potent antioxidant activity and are widely used for treating cardiocerebrovascular diseases. The aim of this work was to investigate the potential interactions between (+)-catechin and puerarin following concurrent oral administration in rats, and their absorption mechanisms in Caco-2 cell monolayers. Methods: Pharmacokinetic studies were conducted in male rats received (+)-catechin (140 mg/kg, po) and/or puerarin (200 mg/kg, po). The cell uptake and transport behavior in Caco-2 cell monolayers and the interactions of the two compounds were analyzed. Results: When (+)-catechin and puerarin were administered concurrently, the AUC0-12 h and Cmax values of puerarin were 2.48-fold and 3.91-fold, respectively, as large as those of puerarin alone; the AUC0-12 h and Cmax values of (+)-catechin were decreased to 57.62% and 77.55%, respectively, compared with those of (+)-catechin alone. In Caco-2 cell monolayers, (+)-catechin (300 and 600 μmol/L) significantly increased the cell uptake and transport of puerarin, whereas puerarin (300 and 600 μmol/L) significantly decreased the cellular uptake and transport of (+)-catechin. Furthermore, both cyclosporine A (P-glycoprotein inhibitor) and MK-571 (MRP-2 inhibitor) significantly increased the cellular uptake and transport of (+)-catechin and puerarin. Conclusion: Concurrent oral administration of (+)-catechin and puerarin significantly increased the absolute oral bioavailability of puerarin, but decreasing that of (+)-catechin. The competitive efflux of (+)-catechin and puerarin by P-glycoprotein and MRP-2 might lead to this interaction during their absorption process in the small intestine. PMID:26972494

  13. Herb-Drug Interaction of Paullinia cupana (Guarana) Seed Extract on the Pharmacokinetics of Amiodarone in Rats.

    PubMed

    Rodrigues, Márcio; Alves, Gilberto; Lourenço, Nulita; Falcão, Amílcar

    2012-01-01

    Paullinia cupana is used in weight-loss programs as a constituent of medicinal/dietary supplements. This study aimed to assess a potential herb-drug interaction among a standardized (certified) Paullinia cupana extract and amiodarone (narrow therapeutic index drug) in rats. In a first pharmacokinetic study rats were simultaneously coadministered with a single dose of Paullinia cupana (821 mg/kg, p.o.) and amiodarone (50 mg/kg, p.o.), and in a second study rats were pretreated during 14 days with Paullinia cupana (821 mg/kg/day, p.o.) receiving amiodarone (50 mg/kg, p.o.) on the 15th day. Rats of the control groups received the corresponding volume of vehicle. Blood samples were collected at several time points after amiodarone dosing, and several tissues were harvested at the end of the experiments (24 h after dose). Plasma and tissue concentrations of amiodarone and its major metabolite (mono-N-desethylamiodarone) were measured and analysed. A significant reduction in the peak plasma concentration (73.2%) and in the extent of systemic exposure (57.8%) to amiodarone was found in rats simultaneously treated with Paullinia cupana and amiodarone; a decrease in tissue concentrations was also observed. This paper reports for the first time an herb-drug interaction between Paullinia cupana extract and amiodarone, which determined a great decrease on amiodarone bioavailability in rats. PMID:23304200

  14. Factors influencing behavior of group-housed male rats in the social interaction test: focus on cohort removal.

    PubMed

    Kask, A; Nguyen, H P; Pabst, R; von Hörsten, S

    2001-10-01

    The rat social interaction (SI) test is used widely to measure anxiety-like behavior, yet the influence of various factors such as testing time, pre-experimental manipulations (transport stress), and testing of animals from the same cage (cohort removal, CR) on SI has not been systematically studied. We measured SI behavior of male triad-housed Wistar rats in a novel dimly lit arena (low light unfamiliar, LU) and found that SI time is higher in the beginning of the activity (dark) phase when compared with SI time in first half of the light phase. Furthermore, SI time is significantly increased by habituation of animals to the testing room during light phase, but this intervention has no effect in early dark phase when SI behavior is already maximal. Sequential removal of rats from the home cage led to the stress-like behavioral and physiological consequences. Rats removed in the last position had shorter SI time and higher body temperature. These data demonstrate that SI is higher during early dark vs. early light phase and confirm that CR has anxiogenic-like effects in rats. We conclude that the usage of sequentially removed group-housed rats in behavioral tests can be a source for considerable variation due to anxiety that develops in animals remaining in the cage. On the other hand, CR may be a useful method to study behavioral/neurochemical mechanisms of psychogenic stress in rats. PMID:11714489

  15. Pharmacokinetic interaction study between flavanones (hesperetin, naringenin) and rasagiline mesylate in wistar rats.

    PubMed

    Pingili, Ravindrababu; Vemulapalli, Sridhar; Mullapudi, Surya Sandeep; Nuthakki, Siddhartha; Pendyala, Sivaprasad; Kilaru, Naveenbabu

    2016-07-01

    Cytochrome P-450 (CYP) enzymes and P-glycoprotein (P-gp) play an important role in the oral bioavailability and first-pass-metabolism (FPM) of many drugs. Rasagiline is a selective, monoamine oxidase-B inhibitor and it undergoes significant FPM in the liver prior to excretion by CYP1A2. Hesperetin and naringenin are naturally occurring flavanones and are reported as modulators of CYP enzymes and P-gp. The objective of the present investigation was to evaluate the effect of hesperetin and naringenin on the pharmacokinetics (PK) of rasagiline in rats. Rats were treated orally with rasagiline (2 mg/kg) alone and co-administered with hesperetin and naringenin (12.5 and 25 mg/kg) for 15 consecutive days. Blood samples were collected from tail vein on the 1st day in a single dose PK study (SDS) and on 15th day in the multiple dose PK study (MDS). Hesperetin and naringenin co-administration significantly enhanced the area under the curve (AUC), maximum plasma concentration (Cmax) and elimination half life (t1/2) of rasagiline with a concomitant reduction in clearance (CL/F) in both SDS and MDS. Rasagiline concentrations were significantly increased when co-administered with hesperetin and naringenin in the brain. No significant difference was found in rasagiline transport from mucosal to serosal side in the presence of hesperetin and naringenin ex vivo (rat everted gut sacs used). Our findings suggested that hesperetin and naringenin enhanced the systemic exposure of rasagiline might be through the inhibition of CYP1A2 but not P-gp. Further studies are needed on CYP1A2 and P-gp over expressed cells to confirm this interaction at cellular level. PMID:26530401

  16. Effects of 6-hydroxydopamine lesioning of the medial prefrontal cortex on social interactions in adolescent and adult rats.

    PubMed

    Li, Chun-Rong; Huang, Guang-Biao; Sui, Zhi Yan; Han, Eui-Hyeog; Chung, Young-Chul

    2010-07-30

    Bilateral depletion of dopamine (DA) in the medial prefrontal cortex (mPFC) following local infusions of 6-hydroxydopamine (6-OHDA) was reported to affect mesolimbic DA neurotransmission and augment spontaneous and amphetamine-induced locomotion. However, the effects of 6-OHDA lesioning of the mPFC of adolescent rats have never been investigated. Given that dopaminergic neurons reach the peak of maturation during adolescence, we hypothesized that 6-OHDA lesioning of the mPFC during adolescence would have greater impact on subsequent behavioral parameters than would such lesioning during adulthood. The aim of this study was to investigate the effects of 6-OHDA lesioning of the mPFC on the open-field activities and novel investigative and socially interactive behaviors of adolescent and adult rats. Using a stereotaxic apparatus, 6-OHDA (8.0 microg) was injected bilaterally into the mPFC of adolescent and adult rats. After a 1-week recovery period, rats were placed in an open-field chamber, and spontaneous locomotion and other behaviors were monitored. Next, a novel toy was place in the center and behavioral responses were observed. One day later, socially interactive behaviors were measured by placing the lesioned rats into a cage with four unfamiliar rats matched for age. The tests of locomotor activity and novel investigative behaviors revealed no significant differences between the lesioned and sham groups of adolescent or adult rats. Grooming and socially interactive behaviors were significantly lower in the adolescent and adult lesioned groups than in each sham group. Interestingly, we observed more extensive impairment in socially interactive behaviors among the adolescent lesioned rats compared to the adult lesioned rats. The present study indicates that DA depletion in the mPFC causes significantly reduced grooming and socially interactive behaviors; this phenomenon may be comparable to the negative symptoms observed in schizophrenia. Further research is

  17. Social interaction with a cagemate in pain facilitates subsequent spinal nociception via activation of the medial prefrontal cortex in rats.

    PubMed

    Li, Zhen; Lu, Yun-Fei; Li, Chun-Li; Wang, Yan; Sun, Wei; He, Ting; Chen, Xue-Feng; Wang, Xiao-Liang; Chen, Jun

    2014-07-01

    Empathy for the pain experience of others can lead to the activation of pain-related brain areas and can even induce aberrant responses to pain in human observers. Recent evidence shows this high-level emotional and cognitive process also exists in lower animals; however, the mechanisms underlying this phenomenon remain unknown. In the present study we found that, after social interaction with a rat that had received subcutaneous injection of bee venom (BV), only the cagemate observer (CO) but not the noncagemate observer (NCO) showed bilateral mechanical hypersensitivity and an enhanced paw flinch reflex following BV injection. Moreover, neuronal activities labeled by c-Fos immunoreactivity in the spinal dorsal horn of CO rats were also significantly increased relative to the control 1 hour after BV injection. A stress-related response can be excluded because serum corticosterone concentration following social interaction with demonstrator rats in pain was not changed in CO rats relative to NCO and isolated control rats. Anxiety can also be excluded because anxiety-like behaviors could be seen in both the CO and NCO rats tested in the open-field test. Finally, bilateral lesions of the medial prefrontal cortex eliminated the enhancement of the BV-induced paw flinch reflex in CO rats, but bilateral lesions of either the amygdala or the entorhinal cortex failed. Together, we have provided another line of evidence for the existence of familiarity-dependent empathy for pain in rats and have demonstrated that the medial prefrontal cortex plays a critical role in processing the empathy-related enhancement of spinal nociception. PMID:24699208

  18. Interactive effects of acupuncture on pain and distress in major burns: An experiment with rats.

    PubMed

    Abali, Ayse Ebru; Cabioglu, Tugrul; Ozdemir, Handan; Haberal, Mehmet

    2015-06-01

    This study sought to investigate the interactive effects of acupuncture on pain and distress and the local progress in the burn wound in an experimental major burn model. Forty-eight male Sprague-Dawley rats were divided into six groups: S group (sham/observation during 7 days after injury); SA group (sham/acupuncture/observation during 7 days after injury); B1 group (burns/observation during 1h after injury); BA1 group (burns/acupuncture/observation during 1 h after injury); B7 group (burns/observation during 7 days after injury); and BA7 group (burns/acupuncture/observation during 7 days after injury). Pain and distress scores were evaluated throughout the study. The amounts of neutrophils and mononuclear cells were evaluated semiquantitatively, and the number of microvessels was evaluated quantitatively. Our data indicated that the average pain score of BA7 group was significantly lower than the other study groups. Histopathologic investigations indicate that the amounts of neutrophil and mononuclear cell and numbers of microvessels in the unburned skin were higher in acupuncture-applied groups. The number of microvessels in burn wounds of BA7 group was significantly higher than that of the other groups. Our data suggest that acupuncture provides low pain and distress scores in experimental rat model, and it contributes to wound healing with an enhanced angiogenesis during the acute phase of burns. Future clinical and experimental studies should be conducted to discern the benefits from acupuncture in pain management of burn patients. PMID:25433758

  19. THC-methadone and THC-naltrexone interactions on discrimination, antinociception, and locomotion in rats.

    PubMed

    Wakley, Alexa A; Craft, Rebecca M

    2011-09-01

    This study examined cannabinoid-opioid interactions within the same subjects on measures of discrimination, antinociception, horizontal locomotion, and catalepsy. Male Sprague-Dawley rats were trained to discriminate Δ(9)-tetrahydrocannabinol (THC, 3 mg/kg) from vehicle. THC alone (0.32-10 mg/kg) dose-dependently increased THC-appropriate lever responding and decreased response rate. THC alone also produced paw pressure antinociception and decreased locomotor activity, but did not produce catalepsy. Methadone (0.32-5.6 mg/kg) and naltrexone (0.32-3.2 mg/kg) alone produced low THC-appropriate lever responding up to doses that decreased response rate. When combined with THC, methadone (1.0 mg/kg) flattened the THC discrimination curve, but did not affect antinociceptive or motoric effects of THC. Naltrexone did not alter any effects of THC. In rats that were not trained to discriminate THC from vehicle, 1.0 mg/kg methadone did enhance THC antinociception. These results suggest that μ-opioid receptor agonists can disrupt the discriminative stimulus effects of cannabinoids while not significantly altering their antinociceptive or motoric effects, in chronically drug-exposed subjects. Further research is required to determine whether opioid enhancement of cannabinoid antinociception is limited to acute exposure, or simply requires higher doses in chronically drug-exposed subjects. PMID:21716095

  20. Interaction between castanospermine an immunosuppressant and cyclosporin A in rat cardiac transplantation

    PubMed Central

    Hibberd, Adrian D; Clark, David A; Trevillian, Paul R; Mcelduff, Patrick

    2016-01-01

    AIM: To investigate the interaction between castanospermine and cyclosporin A (CsA) and to provide an explanation for it. METHODS: The alkaloid castanospermine was prepared from the seeds of Castanospermum austral consistently achieving purity. Rat heterotopic cardiac transplantation and mixed lymphocyte reactivity were done using genetically inbred strains of PVG (donor) and DA (recipient). For the mixed lymphocyte reaction stimulator cells were irradiated with 3000 rads using a linear accelerator. Cyclosporin A was administered by gavage and venous blood collected 2 h later (C2). The blood levels of CsA (Neoral) were measured by immunoassay which consisted of a homogeneous enzyme assay (EMIT) on Cobas Mira. Statistical analyses of interactions were done by an accelerated failure time model with Weibull distribution for allograft survival and logistic regression for the mixed lymphocyte reactivity. RESULTS: Castanospermine prolonged transplant survival times as a function of dose even at relatively low doses. Cyclosporin A also prolonged transplant survival times as a function of dose particularly at doses above 2 mg/kg. There were synergistic interactions between castanospermine and CsA in the prolongation of cardiac allograft survival for dose ranges of CsA by castanospermine of (0 to 2) mg/kg by (0 to 200) mg/kg (HR = 0.986; 95%CI: 0.981-0.992; P < 0.001) and (0 to 3) mg/kg by (0 to 100) mg/kg (HR = 0.986; 95%CI: 0.981-0.992; P < 0.001) respectively. The addition of castanospermine did not significantly increase the levels of cyclosporin A on day 3 or day 6 for all doses of CsA. On the contrary, cessation of castanospermine in the presence of CsA at 2 mg/kg significantly increased the CsA level (P = 0.002). Castanospermine inhibited mixed lymphocyte reactivity in a dose dependent manner but without synergistic interaction. CONCLUSION: There is synergistic interaction between castanospermine and CsA in rat cardiac transplantation. Neither the mixed lymphocyte

  1. Changes in thalamo-frontal interaction under different levels of anesthesia in rats.

    PubMed

    Shin, Teo Jeon; Cho, Dongrae; Ham, Jinsil; Choi, Dong-Hyuk; Kim, Seonghyun; Jeong, Seongwook; Kim, Hyoung-Ihl; Kim, Jae Gwan; Lee, Boreom

    2016-08-01

    Anesthesia is thought to be mediated by inhibiting the integration of information between different areas of the brain. Long-range thalamo-cortical interaction plays a critical role in inducing anesthesia-related unconsciousness. However, it remains unclear how this interaction change according to anesthetic depth. In this study, we aimed to investigate how different levels of anesthesia affect thalamo-frontal interactions. Prior to the experiment, electrodes were implanted to record local field potentials (LFPs). Isoflurane (ISO) was administered and LFPs were measured in rats from four different brain areas (left frontal, right frontal, left thalamus and right thalamus) at four different anesthesia levels: awake, deep (ISO 2.5vol%), light (ISO 1vol%) and recovery. Spectral granger causality (Spectral-GC) were calculated at the measured areas in accordance with anesthetic levels. Anesthesia led to a decrease in connectivity in the thalamo-frontal direction and an increase in connectivity in the frontal-thalamic direction. The changes in thalamo-frontal functional connectivity were prominent during deep anesthesia at high frequency bands. The connection strengths between the thalamus and the frontal area changed depending on the depth of anesthesia. The relationships between anesthetic levels and thalamo-frontal activity may shed light on the neural mechanism by which different levels of anesthesia act. PMID:27230989

  2. Synergistic interaction between tapentadol and flupirtine in the rat orafacial formalin test.

    PubMed

    Lee, Hongki; De Vito, Virginia; Giorgi, Mario; Yun, Hyoin

    2015-09-01

    Combination therapy with two or more analgesics is widely used for conditions associated with moderate to severe pain. Combinations of diverse analgesics with different modes of action can improve the risk-benefit ratio of analgesic treatments. The aim of this study is to evaluate the antinociceptive effect of tapentadol (TAP) and flupirtine (FLP), when administered separately or in combination, as well as their synergistic interaction in the orofacial formalin test in rats. After i.p. injection of TAP at different doses (2, 5, 10 and 15mg/kg), the biphasic nociceptive behavior was reduced in a dose-dependent manner in both phase I and II. Conversely, i.p. injection of FLP at different doses (0.6, 1.6, 3.3, 6.6, 16.6 and 22.2mg/kg) induced a dose-dependent antinociceptive effect in phase II only. TAP was found to be more effective than FLP. The interaction between TAP and FLP was synergistic in phase II with an interaction index (γ) of 0.50±0.24. The data reported in this study indicate that FLP enhances the antinociceptive effect of TAP and this drug combination might be potentially useful in the treatment of chronic pain. PMID:26048311

  3. Potential Interaction of Green Tea Extract with Hydrochlorothiazide on Diuretic Activity in Rats

    PubMed Central

    Chakraborty, Manodeep; Kamath, Jagadish V.; Bhattacharjee, Ananya

    2014-01-01

    Treatment of ischemic hypertensive patients with hydrochlorothiazide can precipitate cardiac arrhythmias. The present study was undertaken to evaluate the diuretic potential of green tea alone and its effects on hydrochlorothiazide in interactive groups. Rats were treated with high (500 mg/kg, p.o.) and low (100 mg/kg, p.o.) dose of green tea extract in alone and interactive groups for 30 days. Standard, high, and low dose interactive groups received hydrochlorothiazide (10 mg/kg, p.o.) on the day of experiment. Effect of different treatments was that assessed by evaluating diuretic action, diuretic activity, percentage of saline load excreted, and sodium and potassium levels in urine. Green tea in both high and low doses showed significant diuretic potential and when it is combined with hydrochlorothiazide resulted in significant improvement in the activity compared to hydrochlorothiazide alone treated group. It can be concluded that green tea extract when combined with hydrochlorothiazide showed significant increase in diuretic activity. Most important observation of the present study is even though the combination increases the diuretic potential, it is responsible for decrease in urinary potassium loss. PMID:27355016

  4. Interactions of aminophylline and three benzodiazepine compounds with amygdala-kindled seizures in rats.

    PubMed

    Albertson, T E; Foulke, G E

    1987-09-01

    Fully amygdala-kindled rats were used to study the effect of diazepam, RO 15-1788, and CGS-8216 on aminophylline-induced prolongation of elicited kindled afterdischarges. Similar proportional reductions in seizure afterdischarge durations were seen with diazepam and with RO 15-1788 after aminophylline although the absolute length of the afterdischarge durations were increased significantly with both drugs after aminophylline. The partial agonist effect of the benzodiazepine antagonist RO 15-1788 was demonstrated before and after aminophylline pretreatment. However, no specific interaction (pro- or anticonvulsant) was demonstrated with the benzodiazepine antagonist CGS-8216 before or after aminophylline pretreatment. Together these data do not support the theory that the prolongation of elicited kindled seizures by the methylxanthine, aminophylline, is through a specific benzodiazepine receptor mechanism. PMID:2887453

  5. Effect of the combination of metformin hydrochloride and melatonin on oxidative stress before and during pregnancy, and biochemical and histopathological analysis of the livers of rats after treatment for polycystic ovary syndrome

    SciTech Connect

    Lemos, Ana Janaina Jeanine M.; Peixoto, Christina A.; Teixeira, Álvaro Aguiar C.; Luna, Rayana Leal A.; Rocha, Sura Wanessa S.; Santos, Hilda Michelly P.; Silva, Amanda Karolina S.; Nunes, Ana Karolina S.; Wanderley-Teixeira, Valéria

    2014-10-01

    The aim of the present study was to analyze the effect of a combination of metformin hydrochloride and melatonin on oxidative stress together with a biochemical and histopathological analysis of the livers of Wistar rats induced with PCOS. The results indicated that a combination of the drugs was more effective in the reduction of plasmatic levels of liver enzyme alanine aminotransferase, nitric oxide and total glutathione, and decreased the inflammatory response and histopathological damage, producing results that were significantly similar to animals from the control group. A mixture of the drugs produced more effective results against liver toxicity caused by PCOS, encouraging the normalization of biochemical parameters. During pregnancy, there was reduced oxidative stress compared to monotherapeutic use of these drugs. Interestingly, the combination of the drugs caused a physiological reaction similar to responses identified in healthy rats without induction of the PCOS control group. However, the clinical and physiological effectiveness of the combination should be further explored, especially with respect to the possible side effects on offspring. - Highlights: • Studies have documented increased oxidative stress in patients with PCOS. • It has been noted that women with PCOS have a high prevalence of liver alterations. • Liver disease in pregnancy may be pre-existing increasing the newborn mortality. • Metformin/melatonin associated reduced oxidative stress in liver in pregnant rats. • Association of metformin/melatonin normalizes hepatic biochemical parameters.

  6. Pharmacokinetic-pharmacodynamic modelling of the convulsant interaction between norfloxacin and biphenyl acetic acid in rats.

    PubMed

    Marchand, S; Pariat, C; Bouquet, S; Courtois, P; Couet, W

    2000-04-01

    Fluoroquinolones (FQs) are associated with a low incidence of central nervous system (CNS) side effects, possibly leading to convulsions, especially when co-administered with nonsteroidal anti-inflammatory drugs (NSAIDS). Although the in vivo pro-convulsant activity of NSAIDS is essentially unknown, the convulsant potential of FQs is traditionally evaluated by in vitro gamma-aminobutyric acid (GABA) binding experiments in the presence of 4-biphenyl acetic acid (BPAA), the active metabolite of fenbufen. The aim of this study was therefore to investigate the BPAA-norfloxacin convulsant interaction in vivo. Male Sprague-Dawley rats (n = 27) were given BPAA orally, at various doses 1 h before norfloxacin infusion, which was maintained until the onset of maximal seizures, when cerebrospinal fluid (CSF) and plasma samples were collected for analysis. An inhibitory E(max) effect model with a baseline effect parameter was fitted to the norfloxacin versus BPAA concentrations in the CSF, previously shown to be part of the biophase. This model includes three parameters: the concentrations of norfloxacin in the absence of BPAA (C(CSF0, Nor)), and when BPAA concentration tends toward infinity (C(CSFbase, Nor)), and the BPAA concentration for which half of the maximal effect is observed (C(CSF50, BPAA)). The maximal proconvulsant effect of BPAA is given by the C(CSF0, Nor) / C(CSFbase, Nor) ratio, estimated to approximately 6 in this study. Derived models were developed in plasma to account for the non-linear CSF diffusion of norfloxacin and protein binding of BPAA. In conclusion this study has shown that the convulsant interaction between norfloxacin and BPAA in rats, can be adequately characterized by modelling of the CSF concentrations of the two drugs at the onset of activity, following their administration in various proportions. PMID:10780965

  7. Pharmacokinetic-pharmacodynamic modelling of the convulsant interaction between norfloxacin and biphenyl acetic acid in rats

    PubMed Central

    Marchand, Sandrine; Pariat, Claudine; Bouquet, Serge; Courtois, Philippe; Couet, William

    2000-01-01

    Fluoroquinolones (FQs) are associated with a low incidence of central nervous system (CNS) side effects, possibly leading to convulsions, especially when co-administered with nonsteroidal anti-inflammatory drugs (NSAIDS). Although the in vivo pro-convulsant activity of NSAIDS is essentially unknown, the convulsant potential of FQs is traditionally evaluated by in vitro γ-aminobutyric acid (GABA) binding experiments in the presence of 4-biphenyl acetic acid (BPAA), the active metabolite of fenbufen.The aim of this study was therefore to investigate the BPAA-norfloxacin convulsant interaction in vivo.Male Sprague-Dawley rats (n=27) were given BPAA orally, at various doses 1 h before norfloxacin infusion, which was maintained until the onset of maximal seizures, when cerebrospinal fluid (CSF) and plasma samples were collected for analysis.An inhibitory Emax effect model with a baseline effect parameter was fitted to the norfloxacin versus BPAA concentrations in the CSF, previously shown to be part of the biophase. This model includes three parameters: the concentrations of norfloxacin in the absence of BPAA (CCSF0, Nor), and when BPAA concentration tends toward infinity (CCSFbase, Nor), and the BPAA concentration for which half of the maximal effect is observed (CCSF50, BPAA). The maximal proconvulsant effect of BPAA is given by the CCSF0, Nor / CCSFbase, Nor ratio, estimated to approximately 6 in this study.Derived models were developed in plasma to account for the non-linear CSF diffusion of norfloxacin and protein binding of BPAA.In conclusion this study has shown that the convulsant interaction between norfloxacin and BPAA in rats, can be adequately characterized by modelling of the CSF concentrations of the two drugs at the onset of activity, following their administration in various proportions. PMID:10780965

  8. Bezafibrate-mizoribine interaction: Involvement of organic anion transporters OAT1 and OAT3 in rats.

    PubMed

    Feng, Yuan; Wang, Changyuan; Liu, Qi; Meng, Qiang; Huo, Xiaokui; Liu, Zhihao; Sun, Pengyuan; Yang, Xiaobo; Sun, Huijun; Qin, Jianhua; Liu, Kexin

    2016-01-01

    A patient with rheumatoid arthritis developed rhabdomyolysis while undergoing treatment with mizoribine concomitantly with bezafibrate. The symptoms rapidly disappeared and laboratory test results normalized when she discontinued the two drugs. The purpose of the present study was to elucidate the transporter-mediated molecular pharmacokinetic mechanisms of drug-drug interactions between bezafibrate and mizoribine. Comparing bezafibrate-mizoribine group with bezafibrate group, the Tmax and Cmax of bezafibrate were essentially unchanged in rats. The AUC of bezafibrate was significantly increased and t1/2β was prolonged markedly with an obviously reduction in plasma clearance and cumulative urinary excretion. The changes were similar to oral studies following intravenous co-administration. In rat kidney slices, the uptake of bezafibrate was markedly inhibited by p-aminohippurate, benzylpenicillin and probenecid but not by tetraethyl ammonium. Mizoribine not only decreased the uptake of bezafibrate, but also inhibited the uptake of p-aminohippurate and benzylpenicillin. The uptakes of bezafibrate and mizoribine were significantly higher compared to vector-HEK293 cells. The uptakes of bezafibrate and mizoribine in highest concentration were increased 1.63 and 1.46 folds in hOAT1-transfected cells, 1.43 and 1.24 folds in hOAT3-transfected cells, respectively. The Km values of bezafibrate uptake by hOAT1/3hOAT1-/hOAT3-HEK293 K293 cells were increased 1.68 fold in hOAT1-HEK293 cell and 2.12 fold in hOAT3-HEK293 cell in the presence of mizoribine with no change of Vmax. It indicated that mizoribine could inhibit the uptake of bezafibrate by hOAT1/3-HEK293 cells in a competitive way. In conclusion, OAT1 and OAT3 are the target transporters of drug-drug interactions between bezafibrate and mizoribine in pharmacokinetic aspects. PMID:26474691

  9. A Novel Bidirectional Interaction between endothelin-3 and Retinoic Acid in Rat Enteric Nervous System Precursors

    PubMed Central

    Gisser, Jonathan M.; Cohen, Ariella R.; Yin, Han; Gariepy, Cheryl E.

    2013-01-01

    Background Signaling through the endothelin receptor B (EDNRB) is critical for the development of the enteric nervous system (ENS) and mutations in endothelin system genes cause Hirschsprung’s aganglionosis in humans. Penetrance of the disease is modulated by other genetic factors. Mutations affecting retinoic acid (RA) signaling also produce aganglionosis in mice. Thus, we hypothesized that RA and endothelin signaling pathways may interact in controlling development of the ENS. Methods Rat immunoselected ENS precursor cells were cultured with the EDNRB ligand endothelin-3, an EDNRB-selective antagonist (BQ-788), and/or RA for 3 or 14 days. mRNA levels of genes related to ENS development, RA- and EDNRB-signaling were measured at 3 days. Proliferating cells and cells expressing neuronal, glial, and myofibroblast markers were quantified. Results Culture of isolated ENS precursors for 3 days with RA decreases expression of the endothelin-3 gene and that of its activation enzyme. These changes are associated with glial proliferation, a higher percentage of glia, and a lower percentage of neurons compared to cultures without RA. These changes are independent of EDNRB signaling. Conversely, EDNRB activation in these cultures decreases expression of RA receptors β and γ mRNA and affects the expression of the RA synthetic and degradative enzymes. These gene expression changes are associated with reduced glial proliferation and a lower percentage of glia in the culture. Over 14 days in the absence of EDNRB signaling, RA induces the formation of a heterocellular plexus replete with ganglia, glia and myofibroblasts. Conclusions A complex endothelin-RA interaction exists that coordinately regulates the development of rat ENS precursors in vitro. These results suggest that environmental RA may modulate the expression of aganglionosis in individuals with endothelin mutations. PMID:24040226

  10. Androgen and FSH synergistically stimulate lipoprotein degradation and utilization by ovary granulosa cells

    SciTech Connect

    Schreiber, J.R.; Nakamura, K.; Schmit, V.; Weinstein, D.B.

    1984-01-01

    Androgen can directly modulate the induction of steroidogenic enzymes by FSH (follicle stimulating hormone) in ovary granulosa cells. In studies of its mechanism of action, the authors examined the androgen effect on granulosa cell interaction with lipoproteins, the physiologic source of cholesterol. After granulosa cells were cultured for 48 hours with and without androgen and/or FSH, the cells were incubated for 24 hours with /sup 125/I-lipoproteins (human high density lipoprotein (HDL), rat HDL, or human low density lipoprotein (LDL)). The media were then analyzed for lipoprotein protein coat degradation products (mainly /sup 125/I-monoiodotyrosine) and progestin (mainly 20 alpha-dihydroprogesterone (20 alpha-DHP)). In the absence of FSH and androgen, 2 X 10(5) granulosa cells degraded basal levels of all three lipoproteins, but produced no measurable 20 alpha-DHP. The addition of 10(-7) M androstenedione (A), testosterone (T), or 5 alpha-dihydrotestosterone (DHT) had no effect on lipoprotein protein degradation or 20 alpha-DHP production. FSH alone stimulated lipoprotein protein degradation by 50 to 300% while the addition of androgen synergistically augmented the FSH-stimulated 20 alpha-DHP production as well as protein coat degradation of all three lipoproteins. DHT and T were both effective, indicating that androgens themselves, and not estrogen products, were responsible for the effect on lipoprotein protein degradation and 20 alpha-DHP production.

  11. Social Interaction and Conditional Self-Discrimination under a Paradigm of Avoidance and Positive Reinforcement in Wistar Rats

    ERIC Educational Resources Information Center

    Penagos-Corzo, Julio C.; Pérez-Acosta, Andrés M.; Hernández, Ingrid

    2015-01-01

    The experiment reported here uses a conditional self-discrimination task to examine the influence of social interaction on the facilitation of self-discrimination in rats. The study is based on a previous report (Penagos- Corzo et al., 2011) showing positive evidence of such facilitation, but extending the exposition to social interaction…

  12. PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTION FOR A BINARY MIXTURE OF CHLORPYRIFOS AND DIAZINON IN THE RAT

    SciTech Connect

    Timchalk, Chuck; Poet, Torka S.; Hinman, Melissa N.; Busby, Andrea L.; Kousba, Ahmed A.

    2005-05-15

    Chlorpyrifos (CPF) and diazinon (DZN) are two commonly used organophosphorus (OP) insecticides and potential exists for concurrent exposures. The primary neurotoxic effects from OP pesticide exposures result from the inhibition of acetylcholinesterase (AChE) by their oxon metabolites. The pharmacokinetic and pharmacodynamic impact of acute binary exposures to CPF and DZN in rats were evaluated in this study. Rats were orally administered CPF, DZN or a CPF/DZN mixture (0, 15, 30 or 60 mg/kg) and blood (plasma and RBC), and brain were collected at 0, 3, 6, 12 and 24 h post-dosing, urine was also collected at 24 h. Chlorpyrifos, DZN and their respective metabolites 3,5,6-trichloro-2-pyridinol (TCP) and 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMHP) were quantified in blood and/or urine and cholinesterase (ChE) inhibition was measured in brain, RBCs and plasma. Co-exposure to CPF/DZN at 15/15 mg/kg, did not appreciably alter the pharmacokinetics of CPF, DZN or their metabolites in blood; whereas, a 60/60 mg/kg dose resulted in a transient increase in Cmax, AUC, and decreased clearance of both compounds, likely due to competition between CPF and DZN for CYP450 metabolism. At lower doses, most likely to be encountered in occupational or environmental exposures, the pharmacokinetics were linear. A dose-dependent inhibition of ChE was noted in tissues for both the single and co-exposures. The overall potency for ChE inhibition was greater for CPF than DZN and the binary mixture response appeared to be strongly influenced by CPF. A comparison of the ChE binary response at the low dose (15 mg/kg), where there were no apparent pharmacokinetic interactions, suggested that the overall ChE response was additive. These are the first reported experiments we are aware of that characterize both the pharmacokinetic and pharmacodynamic interactions between CPF and DZN in the rat, and will be used to further develop a binary physiologically based pharmacokinetic and pharmacodynamic

  13. Interaction between the antioxidant activity of curcumin and cholinergic system on memory retention in adult male Wistar rats

    PubMed Central

    Sarlak, Zeynab; Oryan, Shahrbanoo; Moghaddasi, Mehrnoush

    2015-01-01

    Objective(s): The cholinergic system plays an important role in learning and memory. This study investigated the effects of curcumin (turmeric extract) and the cholinergic system and their interaction on memory retention of passive avoidance learning in adult male Wistar rats. Materials and Methods: At first, an injection cannula was implanted in right ventricles of the animals. One week after the surgery, the animals were trained with a shuttle box set up. Post-training, injections were performed in all experiments. Administration of curcumin increased memory retention. Also administrations of nicotine and pilocarpine, the cholinergic receptor agonists, increased memory retention, while it is decreased by succinylcholine and scopolamine, the cholinergic receptor antagonists. Then co-administration of curcumin and cholinergic drugs were performed. Intraperitoneal and intracerebroventricular injections were applied for the curcumin and cholinergic drugs, respectively. Results: Co-administration of curcumin (45 mg/kg) with a low dose of nicotine (0.1 µg/rat) or pilocarpine (0.5 µg/rat) increased memory retention significantly. Effects of succinylcholine (0.01, 0.1 and 0.5 µg/rat) or scopolamine (0.1, 1 and 5 µg/rat) were attenuated by curcumin markedly (45 mg/kg). Conclusion: The results suggest that curcumin has a close interaction with cholinergic system in memory retention process. PMID:26019804

  14. Investigating herb-drug interactions: the effect of Citrus aurantium fruit extract on the pharmacokinetics of amiodarone in rats.

    PubMed

    Rodrigues, Márcio; Alves, Gilberto; Falcão, Amílcar

    2013-10-01

    Citrus aurantium extract has been largely used in weight loss and sports performance dietary supplements. However, the safety of C. aurantium-containing products has been questioned mainly due to the association of its use with adverse events in the cardiovascular system. Therefore, this work aimed to assess the potential for herb-drug interactions among a standardized C. aurantium extract (GMP certificate) and amiodarone (narrow therapeutic index drug) in rats. In a first pharmacokinetic study, rats were simultaneously co-administered with a single-dose of C. aurantium (164 mg/kg, p.o.) and amiodarone (50 mg/kg, p.o.); in a second study, rats were pre-treated during 14 days with C. aurantium (164 mg/kg/day, p.o.) and received amiodarone (50 mg/kg, p.o.) on the 15th day. Rats of the control groups received the corresponding volume of vehicle. Overall, after analysis of the pharmacokinetic data, it deserves to be highlighted the significant increase of the peak plasma concentration of amiodarone in rats pre-treated with C. aurantium extract, while the extent of systemic exposure was comparable between both groups. This paper reports, for the first time, data on the potential of herb-drug interaction between C. aurantium extract and amiodarone. However, specific clinical trials should be performed to confirm these results in humans. PMID:23886819

  15. Treadmill exercise alleviates stress-induced impairment of social interaction through 5-hydroxytryptamine 1A receptor activation in rats

    PubMed Central

    Kim, Tae-Woon; Lim, Baek-Vin; Kim, Kijeong; Seo, Jin-Hee; Kim, Chang-Ju

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) and its receptors tyrosine kinase B (trkB), and cyclic adenosine monophosphate response element binding protein (CREB) have been suggested as the neurobiological risk factors causing depressive disorder. Serotonin (5-hydroxytryptamine, 5-HT) plays an important role in the pathogenesis of depression. We in-vestigated the effect of treadmill exercise on social interaction in relation with BDNF and 5-HT expressions following stress in rats. Stress was induced by applying inescapable 0.2 mA electric foot shock to the rats for 7 days. The rats in the exercise groups were forced to run on a motorized treadmill for 30 min once a day for 4 weeks. Social interaction test and western blot for BDNF, TrkB, pCREB, and 5-HT1A in the hippocampus were performed. The results indicate that the spend time with unfamiliar partner was decreased by stress, in contrast, treadmill exercise increased the spending time in the stress-induced rats. Expressions of BDNF, TrkB, and pCREB were decreased by stress, in contrast, treadmill exercise enhanced expressions of BDNF, TrkB, and pCREB in the stress-induced rats. In addition, 5-HT1A receptor expression was de-creased by stress, in contrast, treadmill exercise enhanced 5-HT1A expression in the stress-induced rats. In the present study, treadmill exercise alleviated stress-induced social interaction impairment through enhancing hippocampal plasticity and serotonergic function in the hippocampus. These effects of treadmill exercise are achieved through 5-HT1A receptor activation. PMID:26331133

  16. Treadmill exercise alleviates stress-induced impairment of social interaction through 5-hydroxytryptamine 1A receptor activation in rats.

    PubMed

    Kim, Tae-Woon; Lim, Baek-Vin; Kim, Kijeong; Seo, Jin-Hee; Kim, Chang-Ju

    2015-08-01

    Brain-derived neurotrophic factor (BDNF) and its receptors tyrosine kinase B (trkB), and cyclic adenosine monophosphate response element binding protein (CREB) have been suggested as the neurobiological risk factors causing depressive disorder. Serotonin (5-hydroxytryptamine, 5-HT) plays an important role in the pathogenesis of depression. We in-vestigated the effect of treadmill exercise on social interaction in relation with BDNF and 5-HT expressions following stress in rats. Stress was induced by applying inescapable 0.2 mA electric foot shock to the rats for 7 days. The rats in the exercise groups were forced to run on a motorized treadmill for 30 min once a day for 4 weeks. Social interaction test and western blot for BDNF, TrkB, pCREB, and 5-HT1A in the hippocampus were performed. The results indicate that the spend time with unfamiliar partner was decreased by stress, in contrast, treadmill exercise increased the spending time in the stress-induced rats. Expressions of BDNF, TrkB, and pCREB were decreased by stress, in contrast, treadmill exercise enhanced expressions of BDNF, TrkB, and pCREB in the stress-induced rats. In addition, 5-HT1A receptor expression was de-creased by stress, in contrast, treadmill exercise enhanced 5-HT1A expression in the stress-induced rats. In the present study, treadmill exercise alleviated stress-induced social interaction impairment through enhancing hippocampal plasticity and serotonergic function in the hippocampus. These effects of treadmill exercise are achieved through 5-HT1A receptor activation. PMID:26331133

  17. Involvement of the SLIT/ROBO pathway in follicle development in the fetal ovary.

    PubMed

    Dickinson, Rachel E; Hryhorskyj, Lynn; Tremewan, Hannah; Hogg, Kirsten; Thomson, Axel A; McNeilly, Alan S; Duncan, W Colin

    2010-02-01

    In humans and domestic mammals, pivotal processes in ovary development, including primordial follicle assembly, occur prenatally. These events are essential for determining fertility in adult life; however, they remain poorly understood at the mechanistic level. In mammals, the SLITs (SLIT1, SLIT2 and SLIT3) and their ROBO (ROBO1, ROBO2, ROBO3/RIG-1 and ROBO4/MAGIC ROBO) receptors regulate neural, leukocyte, vascular smooth muscle cell and endothelial cell migration. In addition, the SLIT/ROBO pathway has functional roles in embryonic development and in the adult ovary by inhibiting cell migration and promoting apoptosis. We therefore characterised follicle formation and investigated the expression and localisation of the ROBO/SLIT pathway in the ovine fetal ovary. Using RT-PCR, we identified SLIT2, SLIT3, ROBO1, ROBO2 and ROBO4 in sheep ovaries harvested across gestation. The real-time quantitative PCR results implied that ROBO2 expression and ROBO4 expression were elevated during the early stages of follicle formation and stayed abundant during primordial follicle maturation (P<0.05). Immunohistochemistry examination demonstrated that ROBO1 was localised to the pre-granulosa cells, while ROBO2, ROBO4 and SLIT2 were expressed in the oocytes of the developing primordial follicle. This indicates that in the fetal ovary, SLIT-ROBO signalling may require an autocrine and paracrine interaction. Furthermore, at the time of increased SLIT-ROBO expression, there was a significant reduction in the number of proliferating oocytes in the developing ovary (P<0.0001). Overall, these results suggest, for the first time, that the SLIT-ROBO pathway is expressed at the time of follicle formation during fetal ovary development. PMID:19900988

  18. Oxytocin-Dopamine Interactions Mediate Variations in Maternal Behavior in the Rat

    PubMed Central

    Shahrokh, Dara K.; Zhang, Tie-Yuan; Diorio, Josie; Gratton, Alain; Meaney, Michael J.

    2010-01-01

    Variations in maternal behavior among lactating rats associate with differences in estrogen-oxytocin interactions in the medial preoptic area (mPOA) and in dopamine levels in the nucleus accumbens (nAcc). Thus, stable, individual differences in pup licking/grooming (LG) are abolished by oxytocin receptor blockade or treatments that eliminate differences in the nAcc dopamine signal. We provide novel evidence for a direct effect of oxytocin at the level of the ventral tegmental area (VTA) in the regulation of nAcc dopamine levels. Mothers that exhibit consistently increased pup LG (i.e. high LG mothers) by comparison with low LG mothers show increased oxytocin expression in the mPOA and the paraventricular nucleus of the hypothalamus and increased projections of oxytocin-positive cells from both mPOA and paraventricular nucleus of the hypothalamus to the VTA. Direct infusion of oxytocin into the VTA increased the dopamine signal in the nAcc. Finally, high compared with low LG mothers show greater increases in dopamine signal in the nAcc during bouts of pup LG, and this difference is abolished with infusions of an oxytocin receptor antagonist directly into the VTA. These studies reveal a direct effect of oxytocin on dopamine release within the mesocorticolimbic dopamine system and are consistent with previous reports of oxytocin-dopamine interactions in the establishment and maintenance of social bonds. PMID:20228171

  19. In vitro study of lovastatin interactions with amiodarone and with carbon tetrachloride in isolated rat hepatocytes

    PubMed Central

    Krasteva, AZ; Mitcheva, MK; Kondeva-Burdina, MS; Descatoire, VA

    2007-01-01

    AIM: To investigate the interactions at a metabolic level between lovastatin, amiodarone and carbon tetrachloride in isolated rat hepatocytes. METHODS: For cell isolation two-step collagenase liver perfusion was performed. Lovastatin was administered alone in increasing concentrations (1 μmol/L, 3 μmol/L, 5 μmol/L and 10 μmol/L) and in combination with CCl4 (86 μmol/L). The cells were also pretreated with 14 μmol/L amiodarone and then the other two compounds were added. RESULTS: Lovastatin promoted concentration-dependent significant toxicity estimated by decrease in cell viability and GSH level by 45% and 84%, respectively. LDH-activity increased by 114% and TBARS content by 90%. CCl4 induced the expected severe damage on the examined parameters. CCl4 induced toxicity was attenuated after lovastatin pretreatment, which was expressed in less increased values of LDH activity and TBARS levels, as well as in less decreased cell viability and GSH concentrations. However, the pretreatment of hepatocytes with amiodarone abolished the protective effect of lovastatin. CONCLUSION: We suggest that the observed cytopro-tective effect was due to interactions between lovastatin, CCl4 and amiodarone at a metabolic level. PMID:17465501

  20. Reproductive toxicity of the industrial solvent 2-ethoxyethanol in rats and interactive effects of ethanol

    SciTech Connect

    Nelson, B.K.; Brightwell, W.S.; Setzer, J.V.; O'Donohue, T.L.

    1984-08-01

    The solvent, 2-ethoxyethanol, induced complete embryo mortality in pregnant rats exposed to three times the current Federal permissible exposure limit (PEL). Following exposure to ethoxyethanol at a concentration only one-half the current PEL, the offspring evidenced behavioral and neurochemical deviations from controls. Subsequent studies found that ingestion of ethanol with concomitant inhalation of ethoxyethanol vapors early in pregnancy appeared to reduce the number of both behavioral and neurochemical deviations found for ethoxyethanol. In contrast, the concomitant exposure to ethanol and ethoxyethanol later in gestation potentiated the behavioral and neurochemical effects of ethoxyethanol. This research indicates that the industrial solvent 2-ethoxyethanol presents an occupational reproductive hazard and raises the issue of the importance of an interaction of social habits with occupational exposure to such hazards. The results would suggest that occupational physicians should advise pregnant workers in the chemical industry of the adverse effects of ethanol during pregnancy and of the possible interactions with other chemicals and should encourage them to be especially cautious with ethanol consumption since they may be at greater risk.

  1. Ovary cryopreservation and transplantation for fertility preservation.

    PubMed

    Silber, S J

    2012-02-01

    The aim of this review is to summarize the state-of-the-art of ovarian transplantation and cryopreservation. This field has progressed over the last half century from simple animal experiments to sophisticated application in humans. The initial poor results in humans began to improve when a series of nine monozygotic (MZ) twin pairs discordant for premature ovarian failure (POF) underwent ovary transplantation at one center. All of these fresh ovary transplants were successful, resulting in 11 healthy babies in 7 of the 9 recipients. The same surgical techniques were then applied to 3 frozen ovary tissue transplants, up to 14 years after the ovary had been frozen, resulting in 3 more healthy babies. Around the world, the number of healthy babies has now risen to 28. Even ovary allotransplantation is being attempted in the not so uncommon situation where a previous bone marrow donor is now willing to donate ovarian tissue to the same recipient. Recipients routinely reinitiated ovulatory menstrual cycles and normal Day 3 serum FSH levels by 4.5 months. Most conceived naturally (three of them twice or three times from the same graft). The duration of function of fresh ovarian grafts, contrary to initial expectations, indicated minimal oocyte loss from ischemia time. Grafts of just modest portions of ovarian tissue have lasted >7 years. In vitro studies suggest that vitrification of ovarian tissue may be an improvement over the 70% oocyte viability loss from slow freeze. PMID:22205727

  2. Antinociceptive drug interaction between intrathecal vitamin E and gabapentin in the rat formalin test

    PubMed Central

    Kim, Myoung-Joong; Ko, Young-Kwon; Hong, Boo Hwi

    2012-01-01

    Background Gabapentin is thought to exert an effect through the voltage-dependent calcium channel. Vitamin E is a widely known antioxidant which neutralizes the harmful effect of ROS which is considered to play a prominent role in various painful conditions. This study was therefore conducted to assess the antinociceptive effects of gabapentin and vitamin E and the interaction of these drugs in the modulation of pain in rats subjected to a formalin test. Methods Sprague-Dawley rats with a lumbar intrathecal catheter were tested for their paw flinches by 5% formalin injection after intrathecal injection of gabapentin or vitamin E. After obtaining dose-response curves for each drug, the effect of the combination was tested by the total dose fraction value and isobolographic analysis. Results When a single drug was injected intrathecally, significant dose-dependent decreases in flinches were shown only in the late phase. ED50 values of intrathecal gabapentin and vitamin E in the late phase were 75.3 ± 9.58 µg, and 17.56 ± 1.65 mg/kg respectively. The combination of gabapentin and vitamin E produced dose-dependent decreases in the number of flinches in both phases induced by the formalin test. The ED50 value of the combination was lower than the theoretical additive values in the late phase, but did not show a significant difference with the theoretical additive value. Conclusions Gabapentin and vitamin E (by itself) have no antinociceptive effect in the early phase; however their combination has shown an antinociceptive effect. In addition, they show additive effects in the late phase of the formalin test. PMID:23198040

  3. Functional interaction between losartan and central tachykinin NK3 receptors in the conscious rat.

    PubMed Central

    Picard, P; Chrétien, L; Couture, R

    1995-01-01

    1. The cardiovascular and behavioural effects elicted by the intracerebroventricular (i.c.v.) injection of substance P (SP), neurokinin A (NKA), [MePhe7]neurokinin B ([MePhe7]NKB) or angiotensin II (AII) in the conscious rat were assessed before and 5 min after i.c.v. pretreatment with antagonists selective for angiotensin AT1 (losartan and its active metabolite EXP 3174), angiotensin AT2 (PD 123,319) or tachykinin NK3 (R 486) receptors. 2. I.c.v. administration of 25 pmol AII evoked an increase in mean arterial blood pressure (MAP) and water intake behaviour, accompanied by a transient bradycardia, whereas 25 pmol [MePhe7]NKB caused a transient increase in MAP and heart rate (HR) concurrently with marked wet dog shake behaviour. At the same dose, SP and NKA were more potent than [MePhe7]NKB in increasing MAP and HR, but did not produce water intake or wet dog shake behaviours. 3. Losartan (650 pmol, i.c.v.) reduced significantly the cardiovascular and behavioural responses to AII or [MePhe7]NKB, but not to SP or NKA. While 65 pmol losartan was inactive, 260 pmol inhibited selectively the central effects of AII. Whereas EXP 3174 (6.5 nmol) blocked both AII and [MePhe7]NKB-mediated responses, the dose of 650 pmol blocked only the responses to AII. 4. The central responses to AII and [MePhe7]NKB were not affected by PD 123,319 (650 pmol). On the other hand, the [MePhe7]NKB-induced central effects were significnatly reduced by R 486 (650 pmol). The NK3-selective antagonist had no effect against AII. 5. This study provides functional evidence, to support earlier binding data, that losartan (and to some extent its active metabolite EXP 3174) interact with the tachykinin NK3 receptor in rat brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7541280

  4. Interaction between Macrophages and Fibroblasts during Wound Healing of Burn Injuries in Rats.

    PubMed

    Oka, Takeshi; Ohta, Keisuke; Kanazawa, Tomonoshin; Nakamura, Kei-Ichiro

    2016-01-01

    Analysis of the structural changes and cell-to-cell interactions occurring during wound healing of burn injuries is essential to elucidate the morphological characteristics of the reconstitution of tissue architecture. However, conventional approaches do not provide sufficient information with respect to cell-to-cell interactions during wound healing. The aim of this study was to evaluate the interaction between bone marrow-derived cells and resident stromal cells throughout the wound healing of burn injuries, using immunohistochemistry and focused ion beam/scanning electron microscope tomography. We induced third-degree burn injuries on the backs of Wistar rats with a heated cylindrical aluminum block (2.0 cm in diameter). At 7 and 14 days after the burn injuries, the burned skin was immunostained with anti-Iba1 and anti-HSP47 antibodies for visualization of bone marrow-derived cells/macrophages and resident stromal cells/fibroblasts, respectively. Normal skin tissue was used as a control. Double-staining immunohistochemistry revealed frequent contacts between macrophages and fibroblasts and a higher contact ratio in the 3 normal skin compared with burned skin, particularly in the areas of granuloma. Three-dimensional ultrastructural analysis with focused ion beam/scanning electron microscope tomography revealed that macrophages and fibroblasts were located closer together in the normal skin than in the burned skin, confirming the analysis by light microscopic observations and ultrastructural analysis from single sections. These results highlight the importance of contact between macrophages and fibroblasts in the maintenance of skin tissue structure and during wound healing. PMID:27237937

  5. Linkage of regulators of TGF-β activity in the fetal ovary to polycystic ovary syndrome.

    PubMed

    Hatzirodos, Nicholas; Bayne, Rosemary A; Irving-Rodgers, Helen F; Hummitzsch, Katja; Sabatier, Laetitia; Lee, Sam; Bonner, Wendy; Gibson, Mark A; Rainey, William E; Carr, Bruce R; Mason, Helen D; Reinhardt, Dieter P; Anderson, Richard A; Rodgers, Raymond J

    2011-07-01

    Although not often discussed, the ovaries of women with polycystic ovary syndrome (PCOS) show all the hallmarks of increased TGF-β activity, with increased amounts of fibrous tissue and collagen in the ovarian capsule or tunica albuginea and ovarian stroma. Recent studies suggest that PCOS could have fetal origins. Genetic studies of PCOS have also found linkage with a microsatellite located in intron 55 of the extracellular matrix protein fibrillin 3. Fibrillins regulate TGF-β bioactivity in tissues by binding latent TGF-β binding proteins. We therefore examined expression of fibrillins 1-3, latent TGF-β binding proteins 1-4, and TGF-β 1-3 in bovine and human fetal ovaries at different stages of gestation and in adult ovaries. We also immunolocalized fibrillins 1 and 3. The results indicate that TGF-β pathways operate during ovarian fetal development, but most important, we show fibrillin 3 is present in the stromal compartments of fetal ovaries and is highly expressed at a critical stage early in developing human and bovine fetal ovaries when stroma is expanding and follicles are forming. These changes in expression of fibrillin 3 in the fetal ovary could lead to a predisposition to develop PCOS in later life. PMID:21411746

  6. Transcriptomic Analysis of Ovaries from Pigs with High And Low Litter Size

    PubMed Central

    Feng, Yifang; Ding, Yueyun; Ye, Pengfei; Yin, Zongjun

    2015-01-01

    Litter size is one of the most important economic traits for pig production as it is directly related to the production efficiency. Litter size is affected by interactions between multiple genes and the environment. While recent studies have identified some genes associated with prolificacy in pigs, transcriptomic studies of specific genes affecting litter size in porcine ovaries are rare. In order to identify candidate genes associated with litter size in swine, we assessed gene expression differences between the ovaries of Yorkshire pigs with extremely high and low litter sizes using the RNA-Seq method. A total of 1 243 differentially expressed genes were identified: 897 genes were upregulated and 346 genes were downregulated in high litter size ovary samples compared with low litter size ovary samples. A large number of these genes related to steroid hormone regulation in animal ovaries, including 59 Gene Ontology terms and 27 Kyoto Encyclopedia of Genes and Genomes pathways involved in steroid biosynthesis and ovarian steroidogenesis. From these differentially expressed genes, we identified a total of 11 genes using a bioinformatics screen that may be associated with high litter size in Yorkshire pigs. These results provide a list of new candidate genes for porcine litter size and prolificacy to be further investigated. PMID:26426260

  7. Diagnosis and Treatment of Polycystic Ovary Syndrome.

    PubMed

    Williams, Tracy; Mortada, Rami; Porter, Samuel

    2016-07-15

    Polycystic ovary syndrome is the most common endocrinopathy among reproductive-aged women in the United States, affecting approximately 7% of female patients. Although the pathophysiology of the syndrome is complex and there is no single defect from which it is known to result, it is hypothesized that insulin resistance is a key factor. Metabolic syndrome is twice as common in patients with polycystic ovary syndrome compared with the general population, and patients with polycystic ovary syndrome are four times more likely than the general population to develop type 2 diabetes mellitus. Patient presentation is variable, ranging from asymptomatic to having multiple gynecologic, dermatologic, or metabolic manifestations. Guidelines from the Endocrine Society recommend using the Rotterdam criteria for diagnosis, which mandate the presence of two of the following three findings- hyperandrogenism, ovulatory dysfunction, and polycystic ovaries-plus the exclusion of other diagnoses that could result in hyperandrogenism or ovulatory dysfunction. It is reasonable to delay evaluation for polycystic ovary syndrome in adolescent patients until two years after menarche. For this age group, it is also recommended that all three Rotterdam criteria be met before the diagnosis is made. Patients who have marked virilization or rapid onset of symptoms require immediate evaluation for a potential androgen-secreting tumor. Treatment of polycystic ovary syndrome is individualized based on the patient's presentation and desire for pregnancy. For patients who are overweight, weight loss is recommended. Clomiphene and letrozole are first-line medications for infertility. Metformin is the first-line medication for metabolic manifestations, such as hyperglycemia. Hormonal contraceptives are first-line therapy for irregular menses and dermatologic manifestations. PMID:27419327

  8. Linkage of regulators of TGF-β activity in the fetal ovary to polycystic ovary syndrome

    PubMed Central

    Hatzirodos, Nicholas; Bayne, Rosemary A.; Irving-Rodgers, Helen F.; Hummitzsch, Katja; Sabatier, Laetitia; Lee, Sam; Bonner, Wendy; Gibson, Mark A.; Rainey, William E.; Carr, Bruce R.; Mason, Helen D.; Reinhardt, Dieter P.; Anderson, Richard A.; Rodgers, Raymond J.

    2011-01-01

    Although not often discussed, the ovaries of women with polycystic ovary syndrome (PCOS) show all the hallmarks of increased TGF-β activity, with increased amounts of fibrous tissue and collagen in the ovarian capsule or tunica albuginea and ovarian stroma. Recent studies suggest that PCOS could have fetal origins. Genetic studies of PCOS have also found linkage with a microsatellite located in intron 55 of the extracellular matrix protein fibrillin 3. Fibrillins regulate TGF-β bioactivity in tissues by binding latent TGF-β binding proteins. We therefore examined expression of fibrillins 1–3, latent TGF-β binding proteins 1–4, and TGF-β 1–3 in bovine and human fetal ovaries at different stages of gestation and in adult ovaries. We also immunolocalized fibrillins 1 and 3. The results indicate that TGF-β pathways operate during ovarian fetal development, but most important, we show fibrillin 3 is present in the stromal compartments of fetal ovaries and is highly expressed at a critical stage early in developing human and bovine fetal ovaries when stroma is expanding and follicles are forming. These changes in expression of fibrillin 3 in the fetal ovary could lead to a predisposition to develop PCOS in later life.—Hatzirodos, N., Bayne, R. A., Irving-Rodgers, H. F., Hummitzsch, K., Sabatier, L., Lee, S., Bonner, W., Gibson, M. A., Rainey, W. E., Carr, B. R., Mason, H. D., Reinhardt, D. P., Anderson, R. A., Rodgers, R. J. Linkage of regulators of TGF-β activity in the fetal ovary to polycystic ovary syndrome. PMID:21411746

  9. Drug Improves Birth Rates for Women with Ovary Disorder

    MedlinePlus

    ... therapy in increasing live births for women with polycystic ovary syndrome. Letrozole could provide a less expensive, more effective treatment for women with this syndrome. Polycystic ovary syndrome (PCOS) is a leading cause of female infertility. ...

  10. Interaction of Panax quinquefolius Saponin and Dual Antiplatelets on Vascular Endothelial Function in Rats with Acute Myocardial Infarction

    PubMed Central

    Wang, Baojun; Liu, Yue; Shang, Qinghua; Zhang, Qingxiang; Zhang, Lei; Liu, Jiangang; Shi, Dazhuo

    2015-01-01

    The objective of this study is to investigate the interaction of Panax quinquefolius saponin (PQS) and dual antiplatelets (aspirin and clopidogrel) on antiplatelet activity and vascular endothelial function in rats with acute myocardial infarction (AMI). Forty-eight male SD rats were randomly designed into sham group, model group, dual antiplatelet group, and PQS plus dual antiplatelet group. AMI rats were induced by ligation of left anterior descending coronary artery (LAD) and dual antiplatelet agents and additional PQS to dual antiplatelets were intragastrically administered for 28 days, respectively. The ventricular cavity area and cardiac transverse area ratio in PQS + dual antiplatelet group showed a decreased tendency. PAgT(%) decreased significantly in both dual antiplatelet group and PQS + dual antiplatelet group. TXB2 concentration significantly decreased in dual antiplatelet and PQS + dual antiplatelet groups, whereas 6-keto-PGF1α concentration significantly increased in PQS + dual antiplatelet group. Rats in PQS + dual antiplatelet group demonstrated a significant decrease in plasma ET-1 concentration and an increase in serum NO concentration compared with dual antiplatelet group. The combination therapy of PQS and dual antiplatelets showed some beneficial effects on vascular endothelial function and ventricular remodeling in rats with AMI. PMID:26090462

  11. Pharmacokinetic drug interactions between ondansetron and tamoxifen in female Sprague-Dawley rats with DMBA-induced mammary tumor.

    PubMed

    Yang, Si Hyung; Suh, Jung Hwa; Lee, Myung Gull; Kim, So Hee

    2013-02-01

    Tamoxifen, which is used to treat breast cancer, and ondansetron, used for the treatment of chemotherapy-induced nausea, are commonly metabolized via cytochrome P450 (CYP) 2D subfamily and 3A1/2 in rats, as in humans. This study was conducted to investigate the pharmacokinetic interactions between ondansetron and tamoxifen after intravenous and oral administration of ondansetron (both 8 mg/kg) and/or tamoxifen (2 and 10 mg/kg for intravenous and oral administration, respectively), in rats bearing 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammarian tumors (DMBA rats), used as an animal model of human breast cancer. The total area under the plasma concentration-time curve, from time zero to infinity (AUC) of tamoxifen was significantly greater after both intravenous and oral administration with ondansetron, compared to that after administration of tamoxifen-alone. The hepatic and intestinal metabolism of tamoxifen in DMBA rats was inhibited by ondansetron. Taken together, the significant increase in tamoxifen AUC in DMBA rats after intravenous or oral administration with ondansetron may be attributed to non-competitive hepatic (intravenous) and competitive intestinal (oral) inhibition of CYP2D subfamily- and 3A1/2-mediated tamoxifen metabolism by ondansetron. PMID:23393344

  12. Peering into the dynamics of social interactions: measuring play fighting in rats.

    PubMed

    Himmler, Brett T; Pellis, Vivien C; Pellis, Sergio M

    2013-01-01

    Play fighting in the rat involves attack and defense of the nape of the neck, which if contacted, is gently nuzzled with the snout. Because the movements of one animal are countered by the actions of its partner, play fighting is a complex, dynamic interaction. This dynamic complexity raises methodological problems about what to score for experimental studies. We present a scoring schema that is sensitive to the correlated nature of the actions performed. The frequency of play fighting can be measured by counting the number of playful nape attacks occurring per unit time. However, playful defense, as it can only occur in response to attack, is necessarily a contingent measure that is best measured as a percentage (#attacks defended/total # attacks X 100%). How a particular attack is defended against can involve one of several tactics, and these are contingent on defense having taken place; consequently, the type of defense is also best expressed contingently as a percentage. Two experiments illustrate how these measurements can be used to detect the effect of brain damage on play fighting even when there is no effect on overall playfulness. That is, the schema presented here is designed to detect and evaluate changes in the content of play following an experimental treatment. PMID:23353923

  13. Interactions between ADH and prostaglandins in isolated erythrocyte-perfused rat kidney

    SciTech Connect

    Lieberthal, W.; Vasilevsky, M.L.; Valeri, C.R.; Levinsky, N.G.

    1987-02-01

    Interactions between antidiuretic hormone (ADH) and renal prostaglandins in the regulation of sodium reabsorption and urinary concentrating ability were studied in isolated erythrocyte-perfused rat kidneys (IEPK). In this model, hemodynamic characteristics are comparable to those found in vivo, and tubular morphology is preserved throughout the period of perfusion. (Deamino)-D-arginine vasopressin (dDAVP) markedly reduced fractional sodium excretion (FE/sub Na/) in the IEPK. After indomethacin, FE/sub Na/ fell still further. In the absence of dDAVP indomethacin had no effect on sodium excretion. dDAVP increased urine osmolality in the IEPK. When prostaglandin synthesis was blocked with indomethacin, urinary osmolality increased further. In isolated kidneys perfused without erythrocytes (IPK), dDAVP decreased FE/sub Na/ from 14.5 +/- 1.8% to 9.6 +/- 1.2%. dDAVP increased urine osmolality only modestly in the IPK and indomethacin did not increase concentrating ability further. Thus the IEPK (unlike the IPK) can excrete markedly hypertonic urine in response to ADH. ADH also enhances tubular reabsorption of sodium in the IEPK. Prostaglandins inhibit both these actions of ADH but do not directly affect sodium excretion in the absence of the hormone. Prostaglandius were measured by radioimmunoassay.

  14. Experimental study on the mechanical interaction between silicon neural microprobes and rat dura mater during insertion.

    PubMed

    Fekete, Z; Németh, A; Márton, G; Ulbert, I; Pongrácz, A

    2015-02-01

    In vivo insertion experiments are essential to optimize novel neural implants. Our work focuses on the interaction between intact dura mater of rats and as-fabricated single-shaft silicon microprobes realized by deep reactive ion etching. Implantation parameters like penetration force and dimpling through intact dura mater were studied as a function of insertion speed, microprobe cross-section, tip angle and animal age. To reduce tissue resistance, we proposed a unique tip sharpening technique, which was also evaluated in in vivo insertion tests. By doubling the insertion speed (between 1.2 and 10.5 mm/min), an increase of 10-35% in penetration forces was measured. When decreasing the cross-section of the microprobes, penetration forces and dimpling was reduced by as much as 30-50% at constant insertion speeds. Force was noticed to gradually decrease by decreasing tip angles. Measured penetration forces through dura mater were reduced even down to 11±3 mN compared to unsharpened (49±13 mN) probes by utilizing our unique tip sharpening technique, which is very close to exerted penetration force in the case of retracted dura (5±1.5 mN). Our findings imply that age remarkably alters the elasticity of intact dura mater. The decreasing stiffness of dura mater results in a significant rise in penetration force and decrease in dimpling. Our work is the first in vivo comparative study on microelectrode penetration through intact and retracted dura mater. PMID:25631267

  15. Functional diversity and interactions between the repeat domains of rat intestinal lactase.

    PubMed Central

    Jost, B; Duluc, I; Richardson, M; Lathe, R; Freund, J N

    1997-01-01

    Lactase-phlorizin hydrolase (LPH), a major digestive enzyme in the small intestine of newborns, is synthesized as a high-molecular-mass precursor comprising four tandemly repeated domains. Proteolytic cleavage of the precursor liberates the pro segment (LPHalpha) corresponding to domains I and II and devoid of known enzymic function. The mature enzyme (LPHbeta) comprises domains III and IV and is anchored in the brush border membrane via a C-terminal hydrophobic segment. To analyse the roles of the different domains of LPHalpha and LPHbeta, and the interactions between them, we have engineered a series of modified derivatives of the rat LPH precursor. These were expressed in cultured cells under the control of a cytomegalovirus promoter. The results show that recombinant LPHbeta harbouring both domains III and IV produces lactase activity. Neither domain III nor IV is alone sufficient to generate active enzyme, although the corresponding proteins are transport-competent. Tandem duplication of domains III or IV did not restore lactase activity, demonstrating the separate roles of both domains within LPHbeta. Further, the development of lactase activity did not require LPHalpha; however, LPHalpha potentiated the production of active LPHbeta but the individual LPHalpha subdomains I and II were unable to do so. Lactase activity and targeting required the C-terminal transmembrane anchor of LPH; this requirement was terminal transmembrane anchor or LPH; this requirement was not satisfied by the signal/anchor region of another digestive enzyme: sucrase-isomaltase. On the basis of this study we suggest that multiple levels of intramolecular interactions occur within the LPH precursor to produce the mature enzyme, and that the repeat domains of the precursor have distinct and specific functions in protein processing, substrate recognition and catalysis. We propose a functional model of LPHbeta in which substrate is channelled from an entry point located within domain II to

  16. Abnormal gene expression profiles in human ovaries from polycystic ovary syndrome patients.

    PubMed

    Jansen, Erik; Laven, Joop S E; Dommerholt, Henri B R; Polman, Jan; van Rijt, Cindy; van den Hurk, Caroline; Westland, Jolanda; Mosselman, Sietse; Fauser, Bart C J M

    2004-12-01

    Polycystic ovary syndrome (PCOS) represents the most common cause of anovulatory infertility and affects 5-10% of women of reproductive age. The etiology of PCOS is still unknown. The current study is the first to describe consistent differences in gene expression profiles in human ovaries comparing PCOS patients vs. healthy normoovulatory individuals. The microarray analysis of PCOS vs. normal ovaries identifies dysregulated expression of genes encoding components of several biological pathways or systems such as Wnt signaling, extracellular matrix components, and immunological factors. Resulting data may provide novel clues for ovarian dysfunction in PCOS. Intriguingly, the gene expression profiles of ovaries from (long-term) androgen-treated female-to-male transsexuals (TSX) show considerable overlap with PCOS. This observation provides supportive evidence that androgens play a key role in the pathogenesis of PCOS. Presented data may contribute to a better understanding of dysregulated pathways in PCOS, which might ultimately reveal novel leads for therapeutic intervention. PMID:15308691

  17. Interaction of central Angiotensin II and estrogen on systolic blood pressure in female DOCA-salt treated rats

    PubMed Central

    Kafami, Marzieh; Hosseini, Mahmoud; Niazmand, Saeed; Hadjzadeh, Mousa Alreza; Farrokhi, Esmaeil; Mazloum, Tahereh; Shafei, Mohammad Naser

    2016-01-01

    Background: There is a probable interaction of central angiotensin II (Ang II) and estrogen (Est) on blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Therefore, in the present study, the interaction between Ang II and Est in ovariectomized (Ovx) and Sham rats that were treated with DOCA- salt was evaluated. Materials and Methods: The female rats were divided into 10 groups as follows: Sham, Ovx, Sham-DOCA, Ovx-DOCA, Sham-DOCA-estrogen (E), Ovx DOCA-E, Sham-DOCA-losartan (L), Ovx-DOCA-L, Sham–DOCA-L-E, and Ovx-DOCA-L-E. The Est groups received estradiol valerate (2 mg/kg; daily; subcutaneously (s.c)) for four weeks. Following that, several doses of Ang II (0.5, 5, 50, 500, 5000 ng/5 μl) were injected via the intracerebroventricular (i.c.v) route and the changes in systolic blood pressure (SBP) were evaluated. In the losartan groups, 200 μg losartan was injected (i.c.v) 15 minutes after the Ang II injection and the blood pressure was recorded. Treatment by DOCA was performed by removal of one kidney, injection of DOCA (45 mg/kg i.p), and adding of sodium chloride (NaCl) (1%) and potassium chloride (KCl) (0.1%) in the drinking water. Results: The SBP was increased by Ang II and this effect in DOCA-salt treated rat was higher than in the untreated groups. The effect of Ang II on SBP in groups that were treated with Est and L was lower than that in the DOCA-salt groups. Increase in SBP was strongly attenuated by Ang II in groups that were co-treated with both Est and L compared to the DOCA-treated rats. These results showed that Est significantly attenuated the effect of central Ang II on SBP in the DOCA-salt treated rats. Conclusion: We suggest that there are interactions between E and Ang II in the control of blood pressure in DOCA-salt treated rats. PMID:27195251

  18. Melatonin influence in ovary transplantation: systematic review.

    PubMed

    Shiroma, M E; Botelho, N M; Damous, L L; Baracat, E C; Soares-Jr, J M

    2016-01-01

    Melatonin is an indolamine produced by the pineal gland and it can exert a potent antioxidant effect. Its free radical scavenger properties have been used to advantage in different organ transplants in animal experiments. Several concentrations and administration pathways have been tested and melatonin has shown encouraging beneficial results in many transplants of organs such as the liver, lungs, heart, pancreas, and kidneys. The objective of the present study was to review the scientific literature regarding the use of melatonin in ovary transplantation. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was carried out using the Cochrane and Pubmed databases and employing the terms 'melatonin' AND 'ovary' AND 'transplantation.' After analysis, 5 articles were extracted addressing melatonin use in ovary transplants and involving 503 animals. Melatonin enhanced various graft aspects like morphology, apoptosis, immunological reaction, revascularization, oxidative stress, and survival rate. Melatonin's antioxidative and antiapoptotic properties seemingly produce positive effects on ovarian graft activity. Despite the promising results, further studies in humans need to be conducted to consolidate its use, as ovary transplantation for fertility preservation is gradually being moved from the experimental stage to a clinical setting. PMID:27287621

  19. Management of Early Carcinoma of the Ovary

    PubMed Central

    Chapman, George W.

    1988-01-01

    Ovarian cancer represents a formidable challenge to physicians. Early symptoms are nonspecific, and are usually attributed to disorders of the upper gastrointestinal tract. Especially important is suspicion of this neoplasm in its early stage. This article discusses the epidemiology, clinical features, evaluation, and treatment of early carcinomas of the ovary. PMID:3071612

  20. Re-torsion of the ovaries.

    PubMed

    Hyttel, Trine E W; Bak, Geske S; Larsen, Solveig B; Løkkegaard, Ellen C L

    2015-03-01

    The increasing use of de-torsion of the ovaries may result in re-torsion. This review addresses risk of re-torsion and describes preventive strategies to avoid re-torsion in pre-menarcheal girls, and fertile and pregnant women. We clinically reviewed PubMed, Embase, Trip and Cochrane databases. The main outcome measures were re-torsion and viability of ovary with fixation measures. A total of 38 publications including 71 girls, 363 fertile women, and 69 pregnant women were found to be relevant. All studies were case reports or case series, sometimes with non-randomized controls. The studies show considerable heterogeneity in design, population, management and outcome. Only four studies included more than 50 cases. In pregnancy the risk of re-torsion was as high as 19.5-37.5%; among fertile women it was 28.6%. Most articles concluded that fixation of the ovaries to the pelvic sidewall or plication of the ovarian ligament after torsion may prevent re-torsion. In one case a girl experienced re-torsion after ovariopexy. Based on observational studies it seems that de-torsion and fixation of the ovary is a safe procedure that usually ensures maintenance of ovarian function and reduces the risk of recurrence, especially when there are no ovarian cysts or adnexal masses. PMID:25412114

  1. A bovine model for polycystic ovary syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polycystic ovary syndrome (PCOS) results in the greatest single cause of anovulatory infertility in reproductive age women (affecting 5-10%). Previously, research groups have created animal models utilizing non-human primates and sheep to better understand the mechanisms involved in PCOS. However, c...

  2. Interactive toxicity of chlorpyrifos and parathion in neonatal rats: Role of esterases in exposure sequence-dependent toxicity

    SciTech Connect

    Kacham, R.; Karanth, S.; Baireddy, P.; Liu, J.; Pope, C. . E-mail: carey.pope@okstate.edu

    2006-01-15

    We previously reported that sequence of exposure to chlorpyrifos and parathion in adult rats can markedly influence toxic outcome. In the present study, we evaluated the interactive toxicity of chlorpyrifos (8 mg/kg, po) and parathion (0.5 mg/kg, po) in neonatal (7 days old) rats. Rats were exposed to the insecticides either concurrently or sequentially (separated by 4 h) and sacrificed at 4, 8, and 24 h after the first exposure for biochemical measurements (cholinesterase activity in brain, plasma, and diaphragm and carboxylesterase activity in plasma and liver). The concurrently-exposed group showed more cumulative lethality (15/24) than either of the sequential dosing groups. With sequential dosing, rats treated initially with chlorpyrifos prior to parathion (C/P) exhibited higher lethality (7/23) compared to those treated with parathion before chlorpyrifos (P/C; 1/24). At 8 h after initial dosing, brain cholinesterase inhibition was significantly greater in the C/P group (59%) compared to the P/C group (28%). Diaphragm and plasma cholinesterase activity also followed a relatively similar pattern of inhibition. Carboxylesterase inhibition in plasma and liver was relatively similar among the treatment groups across time-points. Similar sequence-dependent differences in brain cholinesterase inhibition were also noted with lower binary exposures to chlorpyrifos (2 mg/kg) and parathion (0.35 mg/kg). In vitro and ex vivo studies compared relative oxon detoxification of carboxylesterases (calcium-insensitive) and A-esterases (calcium-sensitive) in liver homogenates from untreated and insecticide pretreated rats. Using tissues from untreated rats, carboxylesterases detoxified both chlorpyrifos oxon and paraoxon, while A-esterases only detoxified chlorpyrifos oxon. With parathion pretreatment, A-esterases still detoxified chlorpyrifos oxon while liver from chlorpyrifos pretreated rats had little apparent effect on paraoxon. We conclude that while neonatal rats are less

  3. Development of a technique for efficient gene transfer to antral follicular cells in the mouse ovary.

    PubMed

    Sato, Masahiro; Akasaka, Eri; Saitoh, Issei; Ohtsuka, Masato; Watanabe, Satoshi

    2012-06-01

    Ovarian follicle development is a complex process mediated by interactions between oocytes and surrounding follicular cells. In an ovary, oocytes are ultimately released from Graafian follicles, which develop from antral follicles localized near the surface of an ovary. To examine the molecular interaction between these 2 cell types, direct gene transfer to follicular cells as well as oocytes appears to be a promising approach, but few studies have applied this technique. The aim of the present study was to develop a technique for gene transfer to antral follicle cells based on their accessibility near the surface of an ovary. B6C3F1 (a hybrid between C57BL6/N and C3H/HeN) female mice aged 4 or 8 w were anesthesized and their ovaries were exposed. About 100 nl of a solution containing reporter plasmid DNA (0.5 µg/μl) and 0.1% trypan blue was injected into a follicle using a glass micropipette attached to the mouthpiece. A total of 6 follicles were injected per ovary. After injection, the ovary was immediately subjected to in vivo electroporation (EP) using an electroporator with 8 square electric pulses of 50 ms and 50 V. After 24 h, the treated ovaries were excised to examine the expression of reporter constructs by histochemistry. All the injected follicles expressed reporter genes to different extents. Inspection of cryostat sections of ovaries injected with the lacZ expression plasmid demonstrated that 50-100% of follicular cells within a follicle were successfully transfected. However, there were no oocytes within the antral follicles that were negative for such staining (15 follicles tested). Similar results were obtained when the enhanced green fluorescent protein expression plasmid was introduced. The present method based on in vivo EP was found to be very effective for transfection of follicular cells. This approach might be useful to explore the roles of genes related to oogenesis/folliculogenesis, and for reproductive manipulation targeted to antral

  4. Sex-specific effects of early life stress on social interaction and prefrontal cortex dendritic morphology in young rats.

    PubMed

    Farrell, M R; Holland, F H; Shansky, R M; Brenhouse, H C

    2016-09-01

    Early life stress has been linked to depression, anxiety, and behavior disorders in adolescence and adulthood. The medial prefrontal cortex (mPFC) is implicated in stress-related psychopathology, is a target for stress hormones, and mediates social behavior. The present study investigated sex differences in early-life stress effects on juvenile social interaction and adolescent mPFC dendritic morphology in rats using a maternal separation (MS) paradigm. Half of the rat pups of each sex were separated from their mother for 4h a day between postnatal days 2 and 21, while the other half remained with their mother in the animal facilities and were exposed to minimal handling. At postnatal day 25 (P25; juvenility), rats underwent a social interaction test with an age and sex matched conspecific. Distance from conspecific, approach and avoidance behaviors, nose-to-nose contacts, and general locomotion were measured. Rats were euthanized at postnatal day 40 (P40; adolescence), and randomly selected infralimbic pyramidal neurons were filled with Lucifer yellow using iontophoretic microinjections, imaged in 3D, and then analyzed for dendritic arborization, spine density, and spine morphology. Early-life stress increased the latency to make nose-to-nose contact at P25 in females but not males. At P40, early-life stress increased infralimbic apical dendritic branch number and length and decreased thin spine density in stressed female rats. These results indicate that MS during the postnatal period influenced juvenile social behavior and mPFC dendritic arborization in a sex-specific manner. PMID:27180166

  5. Interaction between heat acclimation and exogenous insulin in brown adipose tissue of rats

    NASA Astrophysics Data System (ADS)

    Ohno, H.; Yamashita, H.; Sato, N.; Habara, Y.; Gasa, S.; Nagasawa, J.; Sato, Y.; Ishikawa, M.; Segawa, M.; Yamamoto, M.

    1992-09-01

    Seventy-one male Wistar strain rats (7 weeks old) were kept at 5, 25, or 34° C, respectively, for 2 weeks with or without insulin administration. Insulin (Novo Lente MC) was given subcutaneously in a dose of 3.62 nmol/125 µl saline per 100 g body weight. An apparent effect of insulin treatment was noted only in heat-exposed rats, resulting in a remarkable gain in inter-scapular brown adipose tissue (BAT) mass of heat-acclimated, insulin-treated rats in terms of weight or weight per unit body weight. The BAT from heat-acclimated, insulin-treated rats had significantly higher levels of protein, DNA, RNA, and triglyceride than BAT from heat-acclimated, saline-treated rats. Therefore, it seems likely that the growth of BAT in heat-acclimated, insulin-treated rats was mostly due to the anabolic effects of insulin. The uncoupling protein mRNA was, however, present in BAT of heat-acclimated, insulin-treated rats at rather a depressed level, explaining a corresponding decrease in cold tolerance. On the other hand, the expression of insulin receptor mRNA was attenuated in BAT of rats from all the insulin-treated groups, possibly due to the down-regulation of insulin. Thus, there appeared to be some linkage among BAT, heat acclimation, and insulin.

  6. Effect of ovary induction on bread wheat anther culture: ovary genotype and developmental stage, and candidate gene association.

    PubMed

    Castillo, Ana M; Sánchez-Díaz, Rosa A; Vallés, María P

    2015-01-01

    Ovary pre-conditioned medium and ovary co-culture increased the efficiency of green doubled haploid plant production in bread wheat anther culture. The positive effect of this medium led to a 6- and 11-fold increase in the numbers of embryos and green plants, respectively, having a greater effect on a medium-low responding cultivar. Ovary genotype and developmental stage significantly affected microspore embryogenesis. By the use of Caramba ovaries it was possible to reach a 2-fold increase in the number of embryos and green plants, and to decrease the rate of albinism. Mature ovaries from flowers containing microspores at a late binucleate stage raised the number of embryos and green plants by 25-46% as compared to immature ovaries (excised from flowers with microspores at a mid-late uninucleate stage). The highest numbers of embryos and green plants were produced when using mature Caramba ovaries. Ovaries from Galeón, Tigre, and Kilopondio cultivars successfully induced microspore embryogenesis at the same rate as Caramba ovaries. Moreover, Tigre ovaries raised the percentage of spontaneous chromosome doubling up to 71%. Attempts were made to identify molecular mechanisms associated to the inductive effect of the ovaries on microspore embryogenesis. The genes TAA1b, FLA26, and WALI6 associated to wheat microspore embryogenesis, the CGL1 gene involved in glycan biosynthesis or degradation, and the FER gene involved in the ovary signaling process were expressed and/or induced at different rates during ovary culture. The expression pattern of FLA26 and FER could be related to the differences between genotypes and developmental stages in the inductive effect of the ovary. Our results open opportunities for new approaches to increase bread wheat doubled haploid production by anther culture, and to identify the functional components of the ovary inductive effect on microspore embryogenesis. PMID:26150821

  7. Interaction of prenatal stress and morphine alters prolactin and seizure in rat pups.

    PubMed

    Saboory, Ehsan; Ebrahimi, Loghman; Roshan-Milani, Shiva; Hashemi, Paria

    2015-10-01

    Prenatal exposure to stress and morphine has complicated effects on epileptic seizure. In the present study, effect of prenatal forced-swim stress and morphine co-administration on pentylenetetrazol (PTZ) induced epileptic behaviors and prolactin blood level (PBL) was investigated in rat offspring. Pregnant Wistar rats were divided to four groups of control-saline, control-morphine, stressed-saline and stressed-morphine. In the stressed group, pregnant rats were placed in 25°C water on gestation days 17, 18 and 19 (GD17, GD18 and GD19) for 30 min. In the morphine/saline group, pregnant rats received morphine (10, 12 and 15 mg/kg, IP, on GD17, GD18 and GD19, respectively) or saline (1 ml, IP). In the morphine/saline-stressed group, the rats received morphine or saline and then exposed to stress. On postnatal days 6 and 15 (P6 and P15), blood samples were obtained and PBL was determined. At P15 and P25, the rest of the pups was injected with PTZ to induce seizure. Then, epileptic behaviors of each rat were observed individually. Latency of first convulsion decreased in control-morphine and stressed-saline groups while increased in stressed-morphine rats compared to control-saline group on P15 (P=0.04). Number of tonic-clonic seizures significantly increased in control-morphine and stressed-saline rats compared to control-saline group at P15 (P=0.02). PBL increased in stressed-saline, control-morphine and stress-morphine groups compared to control-saline rats. It can be concluded that prenatal exposure of rats to forced-swim stress and morphine changed their susceptibility to PTZ-induced seizure and PBL during infancy and prepubertal period. Co-administration of morphine attenuated effect of stress on epileptic behaviors. PMID:26056076

  8. Synergistic interaction between nitrogen dioxide and respirable aerosols of sulfuric acid or sodium chloride on rat lungs

    SciTech Connect

    Last, J.A.; Warren, D.L.

    1987-08-01

    We examined interactions in rats between NO/sub 2/ gas and respirable aerosols of sulfuric acid (H/sub 2/SO/sub 4/) or sodium chloride (NaCl). Rats were exposed for 1, 3, or 7 days to 5 ppm of NO/sub 2/ gas, alone or in combination with 1 mg/m3 of H/sub 2/SO/sub 4/ or NaCl aerosols. The apparent rate of collagen synthesis by lung minces was measured after 7 days of exposure, and the protein content of whole lung lavage fluid was measured after 1 or 3 days of exposure. Responses from rats exposed to 5 ppm of NO/sub 2/ alone were significantly different from controls by these assays. A synergistic interaction was demonstrated between 5 ppm of NO/sub 2/ and 1 mg/m3 of either H/sub 2/SO/sub 4/ or NaCl aerosol as evaluated by measurement of the rate of lung collagen synthesis. A synergistic interaction was also demonstrated by the criterion of increased protein content of lung lavage fluid in rats exposed to 5 ppm of NO/sub 2/ and 1 mg/m3 of H/sub 2/SO/sub 4/ aerosol after 1 day of exposure and between 5 ppm of NO/sub 2/ and 1 mg/m3 of NaCl aerosol after 3 days of exposure. These observations with 5 ppm of NO/sub 2/ alone and in combination with 1 mg/m3 of NaCl aerosol support the hypothesis that formation of nitrosyl chloride may contribute to a synergistic interaction between NO/sub 2/ gas and NaCl aerosol. These results suggest that, in general, combinations of oxidant gases with respirable acidic aerosols or with acidogenic gases will demonstrate interactive effects on rat lungs. Such a hypothesis is testable and makes specific predictions about effects of inhalation of pollutant mixtures.

  9. Selective photothermal laser-tissue interaction with augmentation of immunoadjuvants in treatment of DMBA-4 metastatic mammary tumors in rats

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Liu, Hong; Wolf, Roman F.; Lucroy, Michael D.; Nordquist, Robert E.

    2002-09-01

    Induced anti-tumor immunity can be the most effective and long-term cure for cancers, particularly for metastatic tumors. Laser immunotherapy has been developed to induce such immunological responses in rats bearing DMBA-4 metastatic mammary tumors. It involves an intratumoral administration of a laser-absorbing dye (indocyanine green) and a specially formulated immunoadjuvant (glycated chitosan), followed by an irradiation of a near-infrared laser (805-nm diode laser). To understand the immunity induced in this tumor model, immunization using freeze-thaw cell lysates against the DMBA-4 tumors was performed, followed by the tumor challenge twenty-one days later. Also performed is the surgical removal of the primary tumors of the rats before the observation of metastatic tumors. The immunization only delayed the emergence of the primary and metastases in the rats but did not provide immunity against the tumor challenge. After surgical removal of the primary tumors, the tumors re-emerged at the primary sites and the metastases developed at multiple remote sites. In contrast, laser immunotherapy cured rats experienced tumor regression and eradication. Our research has provided strong support for the working mechanism of laser immunotherapy. The experimental results showed that selective photothermal laser-tissue interaction with a complementary use of immunoadjuvant could be a potential therapy for treatment of metastatic tumors by inducing a tumor-specific, long-lasting immunity.

  10. Receptor-mediated gonadotropin action in the ovary. Regulatory role of cyclic nucleotide phosphodiesterase(s) in intracellular adenosine 3′:5′-cyclic monophosphate turnover and gonadotropin-stimulated progesterone production by rat ovarian cells

    PubMed Central

    Azhar, Salman; Menon, K. M. Jairam

    1979-01-01

    The regulatory role of cyclic nucleotide phosphodiesterase(s) and cyclic AMP metabolism in relation to progesterone production by gonadotropins has been studied in isolated rat ovarian cells. Low concentrations of choriogonadotropin (0.4–5ng/ml) increased steroid production without any detectable increase in cyclic AMP, when experiments were carried out in the absence of phosphodiesterase inhibitors. The concentration of choriogonadotropin (10ng/ml) that stimulated progesterone synthesis maximally resulted in a minimal increase in cyclic AMP accumulation and choriogonadotropin binding. Choriogonadotropin at a concentration of 10ng/ml and higher, however, significantly stimulated protein kinase activity and reached a maximum between 250 and 1000ng of hormone/ml. Higher concentrations (50–2500ng/ml) of choriogonadotropin caused an increase in endogenous cyclic AMP, and this increase preceded the increase in steroid synthesis. Analysis of dose–response relationships of gonadotropin-stimulated cyclic AMP accumulation, progesterone production and protein kinase activity revealed a correlation between these responses over a wide concentration range when experiments were performed in the presence of 3-isobutyl-1-methylxanthine. The phosphodiesterase inhibitors papaverine, theophylline and 3-isobutyl-1-methylxanthine each stimulated steroid production in a dose-dependent manner. Incubation of ovarian cells with dibutyryl cyclic AMP or 8-bromo cyclic AMP mimicked the steroidogenic action of gonadotropins and this effect was dependent on both incubation time and nucleotide concentration. Maximum stimulation was obtained with 2mm-dibutyryl cyclic AMP and 8-bromo cyclic AMP, and this increase was close to that produced by a maximally stimulating dose of choriogonadotropin. Other 8-substituted derivatives such as 8-hydroxy cyclic AMP and 8-isopropylthio cyclic AMP, which were less susceptible to phosphodiesterase action, also effectively stimulated steroidogenesis. The

  11. Interactions of ( sup 3 H)amphetamine with rat brain synaptosomes. I. Saturable sequestration

    SciTech Connect

    Zaczek, R.; Culp, S.; Goldberg, H.; Mccann, D.J.; De Souza, E.B. )

    1991-05-01

    Previous studies have identified a saturable site of d-({sup 3}H)amphetamine sequestration (AMSEQ) in rat brain synaptosomes. The present study characterized AMSEQ with respect to its subcellular, neuronal and regional distributions, ontogenetic development, pharmacological specificity and factors required for its maintenance. Although AMSEQ was reduced when assays were performed in Krebs' buffer incubated at 37{degree}C as compared to assays performed in isotonic Tris-sucrose buffer incubated at room temperature, the pharmacological profiles of AMSEQ were virtually identical under both conditions. AMSEQ was negligible in tissues outside the central nervous system, enriched in synaptosomes and partially reduced by striatal kainic acid lesion, indicating neuronal localization. The distribution of AMSEQ in the central nervous system was heterogenous. Highest levels were present in hypothalamus with progressively lower levels noted in parietal cortex, frontal cortex, striatum, thalamus, hippocampus, midbrain, cerebellum, pons-medulla and spinal cord. With regard to its ontogeny, AMSEQ increased early in neonatal life, reaching adult levels by postnatal day 14. Although the effects of amphetamine to abolish the transynaptosomal pH gradient suggest a possible role for this gradient in the maintenance of AMSEQ, the pharmacological profile of AMSEQ indicates that other factors are involved. An interaction with an intrasynaptosomal acid, such as N-acetylaspartate, may account for AMSEQ maintenance. AMSEQ did not possess a stereospecific preference for either d-(IC50 = 177 microM) or I-amphetamine (IC50 = 173 microM). However, the pharmacological profile of AMSEQ indicated structural specificity with antidepressants being relatively potent inhibitors. (Abstract Truncated)

  12. Transient solid-fluid interactions in rat brain tissue under combined translational shear and fixed compression.

    PubMed

    Haslach, Henry W; Leahy, Lauren N; Hsieh, Adam H

    2015-08-01

    An external mechanical insult to the brain may create internal deformation waves, which have shear and longitudinal components that induce combined shear and compression of the brain tissue. To isolate such interactions and to investigate the role of the extracellular fluid (ECF) in the transient mechanical response, translational shear stretch up to 1.25 under either 0 or 33% fixed normal compression is applied without preconditioning to heterogeneous sagittal slices which are nearly the full length of the rat brain cerebrum. The normal stress contribution is estimated by separate unconfined compression stress-stretch curves at 0.0667/s and 1/s engineering strain rates to 33% strain. Unconfined compression deformation causes lateral dimension expansion less than that predicted for an incompressible material under large deformation and often a visible loss of internal fluid from the specimen so that the bulk brain tissue is not incompressible in vitro, as sometimes assumed for mathematical modeling. The response to both slow 0.001/s and moderate 1/s shear translational stretch rates is deformation rate dependent and hardening under no compression but under 33% compression is nearly linear perhaps because of increased solid-solid friction. Both shear and normal stress relaxation are faster after the fast rate deformation possibly because higher deformation rates produce higher ECF hydrostatic pressure that primarily drives stress relaxation. The experimental results on ECF behavior guide the form of our nonlinear viscoelastic mathematical model. Our data are closely fit by non-equilibrium evolution equations that involve at most three specimen-specific empirical parameters and that are based on the idea that stretch of axons and glial processes resists load-induced ECF pressure. PMID:25913604

  13. Aldosterone and thyroid hormone interaction on the sodium and potassium transport pathways of rat colonic epithelium.

    PubMed

    Edmonds, C J; Willis, C L

    1990-01-01

    The effect of hypothyroidism on potassium adaptation (shown by increased potassium secretion in response to potassium loading) and on the action of aldosterone on potassium secretion and sodium fluxes was examined in the rat distal colon. Potassium adaptation, particularly the response to an acute potassium load, was impaired by hypothyroidism which also considerably reduced the rise of transepithelial electrical potential difference (p.d.) of total and transcellular (active) lumen-to-plasma sodium fluxes and of potassium secretion normally produced by aldosterone. These changes were, in part, corrected by a short period (3 days) of tri-iodothyronine replacement. Moreover in aldosterone-treated hypothyroid rats, amiloride in the lumen was considerably less effective in reducing the p.d. and sodium fluxes than in aldosterone-treated normal rats. The intracellular sodium transport pool was greater in the hypothyroid than in the normal rats (5.0 +/- 1.1 (S.E.M.) nmol/mg dry weight compared with 2.9 +/- 0.2 nmol/mg dry weight; P less than 0.02). Aldosterone increased the pool in the normal but not in the hypothyroid rats while amiloride had little effect on the pool in the aldosterone-treated hypothyroid rats but almost abolished it in aldosterone-treated normal rats. Aldosterone plays a major part in the adaptation of colonic sodium and potassium transport to sodium depletion or potassium excess; these adaptations were much impaired in hypothyroid animals. The present results are consistent with a deficiency in aldosterone induction of potassium- and amiloride-sensitive sodium pathways in the apical membrane of colonic epithelial cells in hypothyroid rats, a deficiency which limits the stimulant effect of aldosterone on sodium and potassium transport. PMID:2299278

  14. Nonhuman primate models of polycystic ovary syndrome

    PubMed Central

    Abbott, David H; Nicol, Lindsey E; Levine, Jon E; Xu, Ning; Goodarzi, Mark O; Dumesic, Daniel A

    2013-01-01

    With close genomic and phenotypic similarity to humans, nonhuman primate models provide comprehensive epigenetic mimics of polycystic ovary syndrome (PCOS), suggesting early life targeting for prevention. Fetal exposure to testosterone (T), of all nonhuman primate emulations, provides the closest PCOS-like phenotypes, with early-to-mid gestation T-exposed female rhesus monkeys exhibiting adult reproductive, endocrinological and metabolic dysfunctional traits that are co-pathologies of PCOS. Late gestational T exposure, while inducing adult ovarian hyperandrogenism and menstrual abnormalities, has less dysfunctional metabolic accompaniment. Fetal exposures to dihydrotestosterone (DHT) or diethylstilbestrol (DES) suggest androgenic and estrogenic aspects of fetal programming. Neonatal exposure to T produces no PCOS-like outcome, while continuous T treatment of juvenile females causes precocious weight gain and early menarche (high T), or high LH and weight gain (moderate T). Acute T exposure of adult females generates polyfollicular ovaries, while chronic T exposure induces subtle menstrual irregularities without metabolic dysfunction. PMID:23370180

  15. Dorsal hippocampal NMDA receptors mediate the interactive effects of arachidonylcyclopropylamide and MDMA/ecstasy on memory retrieval in rats.

    PubMed

    Ghaderi, Marzieh; Rezayof, Ameneh; Vousooghi, Nasim; Zarrindast, Mohammad-Reza

    2016-04-01

    A combination of cannabis and ecstasy may change the cognitive functions more than either drug alone. The present study was designed to investigate the possible involvement of dorsal hippocampal NMDA receptors in the interactive effects of arachidonylcyclopropylamide (ACPA) and ecstasy/MDMA on memory retrieval. Adult male Wistar rats were cannulated into the CA1 regions of the dorsal hippocampus (intra-CA1) and memory retrieval was examined using the step-through type of passive avoidance task. Intra-CA1 microinjection of a selective CB1 receptor agonist, ACPA (0.5-4ng/rat) immediately before the testing phase (pre-test), but not after the training phase (post-training), impaired memory retrieval. In addition, pre-test intra-CA1 microinjection of MDMA (0.5-1μg/rat) dose-dependently decreased step-through latency, indicating an amnesic effect of the drug by itself. Interestingly, pre-test microinjection of a higher dose of MDMA into the CA1 regions significantly improved ACPA-induced memory impairment. Moreover, pre-test intra-CA1 microinjection of a selective NMDA receptor antagonist, D-AP5 (1 and 2μg/rat) inhibited the reversal effect of MDMA on the impairment of memory retrieval induced by ACPA. Pre-test intra-CA1 microinjection of the same doses of D-AP5 had no effect on memory retrieval alone. These findings suggest that ACPA or MDMA consumption can induce memory retrieval impairment, while their co-administration improves this amnesic effect through interacting with hippocampal glutamatergic-NMDA receptor mechanism. Thus, it seems that the tendency to abuse cannabis with ecstasy may be for avoiding cognitive dysfunction. PMID:26612394

  16. HPLC-DAD Method for the Pharmacokinetic Interaction Study of Atorvastatin with Pioglitazone and Cholestyramine in Wistar Rats.

    PubMed

    Sharma, Ritesh N; Pancholi, Shyam S

    2014-09-01

    Carotid intima-media thickness is used as a surrogate marker for cardiovascular complications in diabetes mellitus. The combination of atorvastatin and pioglitazone was found to be effective in reducing the thickness of the carotid intima-media layer. The method of RP-HPLC coupled with a diode array detector (DAD) was developed for the pharmacokinetic interaction study of atorvastatin with pioglitazone and cholestyramine, respectively, in Wistar rats. Atorvastatin (ATR) and pioglitazone (PIO) were resolved on a C18 column with a mobile phase composed of 48% methanol, 19% acetonitrile, and 33% 10 mM ammonium formate (v/v/v; pH 3.5±0.3, by formic acid) and a 260 nm detection wavelength on the diode array detector. The method was validated according to international standards with good reproducibility and linear response; mean (r) 0.9987 and 0.9972 to ATR and PIO, respectively. The coefficients of variation of intra- and interassay precision ranged between 4.95-8.12 and 7.29-9.67, respectively. Pharmacokinetic parameters were determined in rats following an oral administration of atorvastatin in the presence and absence of pioglitazone and also with cholestyramine. Compared with the control given atorvastatin alone, the Cmax and AUC of atorvastatin were merely unchanged in rats with the co-administration of pioglitazone, while they decreased by nearly 21 and 15%, respectively, with the concurrent use of cholestyramine. There were no significant changes in Tmax and the plasma half-life (T1/2 ) of atorvastatin in both cases. The performed experiment demonstrated that the presented method was suitable for the estimation and pharmacokinetic interaction study of atorvastatin with pioglitazone and cholestyramine in Wistar rat plasma. PMID:25853068

  17. The effects of phthalates on the ovary.

    PubMed

    Hannon, Patrick R; Flaws, Jodi A

    2015-01-01

    Phthalates are commonly used as plasticizers in the manufacturing of flexible polyvinyl chloride products. Large production volumes of phthalates and their widespread use in common consumer, medical, building, and personal care products lead to ubiquitous human exposure via oral ingestion, inhalation, and dermal contact. Recently, several phthalates have been classified as reproductive toxicants and endocrine-disrupting chemicals based on their ability to interfere with normal reproductive function and hormone signaling. Therefore, exposure to phthalates represents a public health concern. Currently, the effects of phthalates on male reproduction are better understood than the effects on female reproduction. This is of concern because women are often exposed to higher levels of phthalates than men through their extensive use of personal care and cosmetic products. In the female, a primary regulator of reproductive and endocrine function is the ovary. Specifically, the ovary is responsible for folliculogenesis, the proper maturation of gametes for fertilization, and steroidogenesis, and the synthesis of necessary sex steroid hormones. Any defect in the regulation of these processes can cause complications for reproductive and non-reproductive health. For instance, phthalate-induced defects in folliculogenesis and steroidogenesis can cause infertility, premature ovarian failure, and non-reproductive disorders. Presently, there is a paucity of knowledge on the effects of phthalates on normal ovarian function; however, recent work has established the ovary as a target of phthalate toxicity. This review summarizes what is currently known about the effects of phthalates on the ovary and the mechanisms by which phthalates exert ovarian toxicity, with a particular focus on the effects on folliculogenesis and steroidogenesis. Further, this review outlines future directions, including the necessity of examining the effects of phthalates at doses that mimic human exposure

  18. The Effects of Phthalates on the Ovary

    PubMed Central

    Hannon, Patrick R.; Flaws, Jodi A.

    2015-01-01

    Phthalates are commonly used as plasticizers in the manufacturing of flexible polyvinyl chloride products. Large production volumes of phthalates and their widespread use in common consumer, medical, building, and personal care products lead to ubiquitous human exposure via oral ingestion, inhalation, and dermal contact. Recently, several phthalates have been classified as reproductive toxicants and endocrine-disrupting chemicals based on their ability to interfere with normal reproductive function and hormone signaling. Therefore, exposure to phthalates represents a public health concern. Currently, the effects of phthalates on male reproduction are better understood than the effects on female reproduction. This is of concern because women are often exposed to higher levels of phthalates than men through their extensive use of personal care and cosmetic products. In the female, a primary regulator of reproductive and endocrine function is the ovary. Specifically, the ovary is responsible for folliculogenesis, the proper maturation of gametes for fertilization, and steroidogenesis, and the synthesis of necessary sex steroid hormones. Any defect in the regulation of these processes can cause complications for reproductive and non-reproductive health. For instance, phthalate-induced defects in folliculogenesis and steroidogenesis can cause infertility, premature ovarian failure, and non-reproductive disorders. Presently, there is a paucity of knowledge on the effects of phthalates on normal ovarian function; however, recent work has established the ovary as a target of phthalate toxicity. This review summarizes what is currently known about the effects of phthalates on the ovary and the mechanisms by which phthalates exert ovarian toxicity, with a particular focus on the effects on folliculogenesis and steroidogenesis. Further, this review outlines future directions, including the necessity of examining the effects of phthalates at doses that mimic human exposure

  19. Complementary Therapy in Polycystic Ovary Syndrome

    PubMed Central

    Aquino, C. I.; Nori, S. L.

    2014-01-01

    Polycystic Ovary Syndrome (PCOS) is an endocrine disease. PCOS afflicts 5 to 10 % of women of reproductive age. The symptoms are: amenorrhea, oligomenorrhea, hirsutism, obesity, infertility, chronic hyperandrogenic anovulation and acne. Other risk factors aggravate this condition: insulin resistance, obesity, hypertension, dyslipidemia, inflammation and subclinical cardiovascular disease. Anxiety, depression and reduced quality of life are also common. This review highlights the mechanisms and the beneficial effects of acupuncture, exercise and resveratrol on animal models and on humans affected by PCOS. PMID:24809037

  20. Autoimmunity to endometrium and ovary in endometriosis.

    PubMed Central

    Mathur, S; Peress, M R; Williamson, H O; Youmans, C D; Maney, S A; Garvin, A J; Rust, P F; Fudenberg, H H

    1982-01-01

    Antibody titres to whole ovary, theca cells, granulosa cells and endometrium were determined by passive haemagglutination and immunofluorescence assays in sera and in cervical and vaginal secretions from 13 patients with endometriosis. Antibody titres to endometrium (mean log2 +/- s.e.m., 7.08 +/- 0.80; P less than 0.0001), ovary (3.58 +/- 0.87; P = 0.0092), theca cells (4.42 +/- 0.73; P less than 0.0001) and granulosa cells (3.33 +/- 0.63; P = 0.0024) were significantly higher in the patients' sera than in sera from 15 normal non-pregnant females. Antibody titres to granulosa cells were elevated (7.97 +/- 1.46; P = 0.0424) in their cervical secretions. Antibody titres to all tissues tested were similar in vaginal secretions of patients and controls. Immunofluorescent antibody assay of biopsied endometrial tissue and sera from the patients revealed the antibodies to be primarily IgG and IgA. The results suggest that autoantibodies to endometrium and ovary are present in patients with endometriosis. Images Fig. 1 Fig. 2 Fig. 3 PMID:6759000

  1. Lymphangioma of the ovary: etiology and management.

    PubMed

    Radhouane, Achour; Mayada, Saadaoui; Khaled, Neji

    2016-08-01

    Lymphangioma of the ovary is an extremely rare lesion. It was first described in 1908 [1] and there is only 19 cases reports in a 50-year literature survey [2]. Lymphangiomas are benign congenital malformations of lymphatic system. They are thought to happen due to obstruction of local lymph flow system and they can occur anywhere in the skin and the mucous membranes. Most common sites are the head and the neck and sometimes they can be found in the intestines, the pancreas and the mesentery. Lymphangioma of the ovary is a very rare tumor. Typically, lymphangiomas are slow-growing tumors that remain asymptomatic for a long time, with the tumor being identified incidentally during histopathological examination after excision. A 36-year-old women who consulted our department for infertility for 2 years. The systematic ultrasound examination reveals a right ovarian mass. The histologic analysis confirmed the diagnosis of cystic lymphangioma of the right ovary. She was planned for total laparoscopic tumorectomy with removal of all ovarian mass. The evolution was good for one year within Clinical and ultrasound monitoring. We report through this case report a review of the literature. PMID:27401696

  2. Melamine Induces Oxidative Stress in Mouse Ovary

    PubMed Central

    Dai, Xiao-Xin; Duan, Xing; Cui, Xiang-Shun; Kim, Nam-Hyung; Xiong, Bo; Sun, Shao-Chen

    2015-01-01

    Melamine is a nitrogen heterocyclic triazine compound which is widely used as an industrial chemical. Although melamine is not considered to be acutely toxic with a high LD50 in animals, food contaminated with melamine expose risks to the human health. Melamine has been reported to be responsible for the renal impairment in mammals, its toxicity on the reproductive system, however, has not been adequately assessed. In the present study, we examined the effect of melamine on the follicle development and ovary formation. The data showed that melamine increased reactive oxygen species (ROS) levels, and induced granulosa cell apoptosis as well as follicle atresia. To further analyze the mechanism by which melamine induces oxidative stress, the expression and activities of two key antioxidant enzymes superoxide dismutase (SOD) and glutathi-one peroxidase (GPX) were analyzed, and the concentration of malondialdehyde (MDA) were compared between control and melamine-treated ovaries. The result revealed that melamine changed the expression and activities of SOD and GPX in the melamine-treated mice. Therefore, we demonstrate that melamine causes damage to the ovaries via oxidative stress pathway. PMID:26545251

  3. Polycystic ovary syndrome: symptomatology, pathophysiology, and epidemiology.

    PubMed

    Guzick, D

    1998-12-01

    Women with polycystic ovary syndrome seek health care for 3 major reasons: infertility, menstrual irregularity, and androgen excess. The infertility is associated with anovulation. The menstrual irregularity is typically chronic, beginning with menarche. Although amenorrhea may sometimes occur, the more common presentation is irregular bleeding characteristic of anovulation. Androgen excess may be manifested by varying degrees of hirsutism. Patients may also report acne. The rapid development of virilizing signs, such as deepening of the voice, increased muscle mass, and temporal balding, should prompt a search for a tumor and lead one away from a diagnosis of polycystic ovary syndrome. Typically treatment is directed at alleviating the symptoms: ovulation induction for infertility, oral contraceptives or a progestin for menstrual irregularity, and oral contraceptives or spironolactone for hirsutism. On the basis of recent epidemiologic data suggestive of increased cardiovascular risk among women with polycystic ovary syndrome, such treatment might be complemented by a long-term approach that addresses the underlying pathophysiology of insulin resistance. PMID:9855614

  4. Trace Elements in Ovaries: Measurement and Physiology.

    PubMed

    Ceko, Melanie J; O'Leary, Sean; Harris, Hugh H; Hummitzsch, Katja; Rodgers, Raymond J

    2016-04-01

    Traditionally, research in the field of trace element biology and human and animal health has largely depended on epidemiological methods to demonstrate involvement in biological processes. These studies were typically followed by trace element supplementation trials or attempts at identification of the biochemical pathways involved. With the discovery of biological molecules that contain the trace elements, such as matrix metalloproteinases containing zinc (Zn), cytochrome P450 enzymes containing iron (Fe), and selenoproteins containing selenium (Se), much of the current research focuses on these molecules, and, hence, only indirectly on trace elements themselves. This review focuses largely on two synchrotron-based x-ray techniques: X-ray absorption spectroscopy and x-ray fluorescence imaging that can be used to identify the in situ speciation and distribution of trace elements in tissues, using our recent studies of bovine ovaries, where the distribution of Fe, Se, Zn, and bromine were determined. It also discusses the value of other techniques, such as inductively coupled plasma mass spectrometry, used to garner information about the concentrations and elemental state of the trace elements. These applications to measure trace elemental distributions in bovine ovaries at high resolutions provide new insights into possible roles for trace elements in the ovary. PMID:26864198

  5. Effects of trifluralin on the mouse ovary.

    PubMed

    Cecconi, Sandra; Rossi, Gianna; Carta, Gaspare; Di Luigi, Gianluca; Cellini, Valerio; Canipari, Rita; Buccione, Roberto

    2013-04-01

    Trifluralin, a herbicide used to protect many arable and horticultural crops, was evaluated for its potential toxicity on the mammalian ovary. To this end, adult female mice were fed or not (control) with a trifluralin-enriched diet (150 mg/kg body weight/day) during gestation and lactation. After weaning, 3-week-old female mice from either trifluralin-treated or control groups were used to evaluate whether the exposure to this herbicide in utero and during lactation could induce stress responses in the ovary. It was found that trifluralin exposure caused a significantly higher level of p53, but not of pRb, in the whole ovary, and in particular in granulosa cells. TUNEL staining showed that herbicide treatment did not increase the apoptotic index of the somatic compartment. Also oocyte fertilizability was unaffected, as metaphase II oocytes retrieved from treated mice were capable of forming male and female pronuclei after in vitro fertilization as control mice. However, trifluralin determined a slightly higher number of oocytes with cytoplasmic degeneration compared with control animals. In conclusion, our results suggest that exposure to a low trifluralin dose during pregnancy and lactation does not impair oocyte quality, but can induce a stress response in ovarian somatic cells. PMID:21544921

  6. Mood disorders and quality of life in polycystic ovary syndrome.

    PubMed

    Podfigurna-Stopa, Agnieszka; Luisi, Stefano; Regini, Cristina; Katulski, Krzysztof; Centini, Gabriele; Meczekalski, Blazej; Petraglia, Felice

    2015-06-01

    Polycystic ovary syndrome (PCOS) affects 5-10% of the population of women. The exact etiology of PCOS remains unclear, but it is believed to result from complex interactions between genetic, behavioral and environmental factors. The spectrum of its symptoms such as hirsutism, skin problems, obesity and finally infertility has a huge negative impact on the individuals' psychological and interpersonal functioning. PCOS symptoms can lead to significant deterioration in quality of life and be highly stressful negatively affecting psychological well-being and sexuality. Fear symptoms like palpitation, being out of breath and tension might be caused by many somatic diseases. Moreover, detection and continuous thinking about illness can lead to significant negative impact on individual functioning in society. PCOS may be a factor potentially favoring the occurrence of mood disorders and depression. Biological, social and psychological consequences of PCOS among women of reproductive age are opening a new perspective on management of women's health in these patients. PMID:26204044

  7. Morphine-induced trafficking of a mu-opioid receptor interacting protein in rat locus coeruleus neurons.

    PubMed

    Jaremko, Kellie M; Thompson, Nicholas L; Reyes, Beverly A S; Jin, Jay; Ebersole, Brittany; Jenney, Christopher B; Grigson, Patricia S; Levenson, Robert; Berrettini, Wade H; Van Bockstaele, Elisabeth J

    2014-04-01

    Opiate addiction is a devastating health problem, with approximately 2million people currently addicted to heroin or non-medical prescription opiates in the United States alone. In neurons, adaptations in cell signaling cascades develop following opioid actions at the mu opioid receptor (MOR). A novel putative target for intervention involves interacting proteins that may regulate trafficking of MOR. Morphine has been shown to induce a re-distribution of a MOR-interacting protein Wntless (WLS, a transport molecule necessary for secretion of neurotrophic Wnt proteins), from cytoplasmic to membrane compartments in rat striatal neurons. Given its opiate-sensitivity and its well-characterized molecular and cellular adaptations to morphine exposure, we investigated the anatomical distribution of WLS and MOR in the rat locus coeruleus (LC)-norepinephrine (NE) system. Dual immunofluorescence microscopy was used to test the hypothesis that WLS is localized to noradrenergic neurons of the LC and that WLS and MOR co-exist in common LC somatodendritic processes, providing an anatomical substrate for their putative interactions. We also hypothesized that morphine would influence WLS distribution in the LC. Rats received saline, morphine or the opiate agonist [d-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin (DAMGO), and tissue sections through the LC were processed for immunogold-silver detection of WLS and MOR. Statistical analysis showed a significant re-distribution of WLS to the plasma membrane following morphine treatment in addition to an increase in the proximity of gold-silver labels for MOR and WLS. Following DAMGO treatment, MOR and WLS were predominantly localized within the cytoplasmic compartment when compared to morphine and control. In a separate cohort of rats, brains were obtained from saline-treated or heroin self-administering male rats for pulldown co-immunoprecipitation studies. Results showed an increased association of WLS and MOR following heroin exposure. As the

  8. Morphine-induced trafficking of a mu-opioid receptor interacting protein in rat locus coeruleus neurons

    PubMed Central

    Jaremko, Kellie M.; Thompson, Nicholas L.; Reyes, Beverly A. S.; Jin, Jay; Ebersole, Brittany; Jenney, Christopher B.; Grigson, Patricia S.; Levenson, Robert; Berrettini, Wade H.; Van Bockstaele, Elisabeth J.

    2014-01-01

    Opiate addiction is a devastating health problem, with approximately 2 million people currently addicted to heroin or non-medical prescription opiates in the United States alone. In neurons, adaptations in cell signaling cascades develop following opioid actions at the mu opioid receptor (MOR). A novel putative target for intervention involves interacting proteins that may regulate trafficking of MOR. Morphine has been shown to induce a re-distribution of a MOR-interacting protein Wntless (WLS, a transport molecule necessary for secretion of neurotrophic Wnt proteins), from cytoplasmic to membrane compartments in rat striatal neurons. Given its opiate-sensitivity and its well-characterized molecular and cellular adaptations to morphine exposure, we investigated the anatomical distribution of WLS and MOR in the rat locus coeruleus (LC)-norepinephrine (NE) system. Dual immunofluorescence microscopy was used to test the hypothesis that WLS is localized to noradrenergic neurons of the LC and that WLS and MOR co-exist in common LC somatodendritic processes, providing an anatomical substrate for their putative interactions. We also hypothesized that morphine would influence WLS distribution in the LC. Rats received saline, morphine or the opiate agonist [D-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin (DAMGO), and tissue sections through the LC were processed for immunogold-silver detection of WLS and MOR. Statistical analysis showed a significant re-distribution of WLS to the plasma membrane following morphine treatment in addition to an increase in the proximity of gold-silver labels for MOR and WLS. Following DAMGO treatment, MOR and WLS were predominantly localized within the cytoplasmic compartment when compared to morphine and control. In a separate cohort of rats, brains were obtained from saline-treated or heroin self-administering male rats for pulldown co-immunoprecipitation studies. Results showed an increased association of WLS and MOR following heroin exposure. As

  9. Transcriptomic analysis of different stages of pigeon ovaries by RNA-sequencing.

    PubMed

    Xu, Xiaoqin; Zhao, Xuting; Lu, Lizhi; Duan, Xiujun; Qin, Haorong; Du, Xue; Li, Guoqin; Tao, Zhengrong; Zhong, Shengliang; Wang, Genlin

    2016-07-01

    The pigeon ovary is an ideal model for deciphering the molecular mechanism of folliculogenesis. While most analysis has focused on the influence of hormones and factors on ovarian follicle development in this model, changes occurring in the ovarian stroma can also be extremely informative. Here, we profiled the transcriptome of pigeon ovaries at pre-ovulation, post-ovulation, and 5-6 days after ovulation using RNA-sequencing to gain insights into the molecular and cellular events mediating ovary activity. We obtained 44,784,505 clean reads that aligned with 14,088 genes. Gene expression profile analysis identified 409 differentially expressed genes between pre- and post-ovulation; 96 genes were up-regulated genes while 313 genes were down-regulated. Gene ontology analysis of the down-regulated genes revealed significant enrichment in components of the immune response, immune system, antigen processing and presentation, receptor binding, and biological adhesion. Pathway analyses of the high-expression genes of the post-ovulation ovary identified enrichment in phagosomes, lysosomes, cytokine-cytokine receptor interactions, cell adhesion molecules, and the Toll-like receptor signaling. These data together suggest that post-ovulatory follicle regression and elimination occurs through an immune response. Mol. Reprod. Dev. 83: 640-648, 2016. © 2016 Wiley Periodicals, Inc. PMID:27404894

  10. Involvement of nitric oxide in inflammation of ovaries in gilts.

    PubMed

    Jana, Barbara; Andronowska, Aneta; Kucharski, Jan

    2002-03-01

    NADPH-diaphorase (NADPH-d) and an inducible type of nitric oxide synthase (iNOS) were demonstrated in porcine ovaries after unilateral infusion of bacteria into the hilus of an ovary. In group I one ml of saline was infused into the hilus of each ovary from the 15th day to the 19th day of the estrous cycle. In group II one ml of bacterial suspension (10(9) colony forming units of Escherichia coli, Staphylococcus aureus and Corynebacterium pyogenes, in a proportion 1:1:1, respectively) in saline was infused into the hilus of one ovary on days corresponding to those of the control group (gr. I), whereas saline was infused into the contralateral ovary. The ovaries were collected on the 7th day of the next estrous cycle. In the bacteria-treated ovary, the activity of NADPH-d was higher in the endothelium of blood vessels, corpora lutea and follicular walls in comparison to that observed in the respective structures of the contralateral ovary. The highest activity of NADPH-d was found in the vascular endothelium in the bacteria-infused ovary. Vascular smooth muscle cells found in both ovaries of the bacteria-treated gilts were more intensely stained for NADPH-d than those in control animals. After bacteria administration, the intensity of NADPH-d reaction in all the structures of both ovaries in group II was higher than in control group. The strongest immunostaining for iNOS was observed in all structures of the bacteria-infused ovary. In the contralateral ovary, iNOS-immunoreactivity was weaker but still stronger than that in control group. The present results revealed that infusions of bacteria into the hilus of one ovary enhanced the activity of NADPH-d and immunoreactivity for iNOS in both porcine ovaries. However, the activity of both enzymes was higher in the bacteria-infused ovary than in the contralateral one. These data suggest that locally synthesized NO can mediate an inflammatory effect of bacteria in the porcine ovaries. PMID:14666163

  11. Interaction of vitamin E and exercise training on oxidative stress and antioxidant enzyme activities in rat skeletal muscles.

    PubMed

    Chang, Chen-Kang; Huang, Hui-Yu; Tseng, Hung-Fu; Hsuuw, Yan-Der; Tso, Tim K

    2007-01-01

    It has been shown that free radicals are increased during intensive exercise. We hypothesized that vitamin E (vit E) deficiency, which will increase oxidative stress, would augment the training-induced adaptation of antioxidant enzymes. This study investigated the interaction effect of vit E and exercise training on oxidative stress markers and activities of antioxidant enzymes in red quadriceps and white gastrocnemius of rats in a 2x2 design. Thirty-two male rats were divided into trained vit E-adequate, trained vit E-deficient, untrained vit E-adequate, and untrained vit E-deficient groups. The two trained groups swam 6 h/day, 6 days/week for 8 weeks. The two vit E-deficient groups consumed vit E-free diet for 8 weeks. Vitamin E-training interaction effect was significant on thiobarbituric acid reactive substances (TBARSs), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in both muscles. The trained vit E-deficient group showed the highest TBARS and GPX activity and the lowest SOD activity in both muscles. A significant vit E effect on glutathione reductase and catalase was present in both muscles. Glutathione reductase and catalase activities were significantly lower in the two vit E-adequate groups combined than in the two vit E-deficient groups combined in both muscles. This study shows that vit E status and exercise training have interactive effect on oxidative stress and GPX and SOD activities in rat skeletal muscles. Vitamin E deprivation augmented the exercise-induced elevation in GPX activity while inhibiting exercise-induced SOD activity, possibly through elevated oxidative stress. PMID:16644199

  12. Synergistic interaction between metformin and sulfonylureas on diclofenac-induced antinociception measured using the formalin test in rats

    PubMed Central

    Ortiz, Mario I

    2013-01-01

    BACKGROUND There is evidence that biguanides and sulfonylureas block diclofenac-induced antinociception (DIA) in rat models. However, little is known about the interaction between these hypoglycemics with respect to DIA. OBJECTIVE: To determine whether metformin-sulfonylurea combinations affect DIA during the formalin test. METHODS: Rats received the appropriate vehicle or diclofenac before 1% formaldehyde was injected into the paw. Rats were also pretreated with vehicle, glibenclamide, glipizide, metformin or glibenclamide/metformin and glipizide/metformin combinations before the diclofenac and formaldehyde injections, and the effect on antinociception was assessed. Isobolograms of the combinations were constructed to test for a synergistic interaction. RESULTS: Systemic injection of diclofenac resulted in antinociception during the second phase of the test. Systemic pretreatment with the combinations of glibenclamide (0.56 mg/kg to 10 mg/kg)/metformin (10 mg/kg to 180 mg/kg) and glipizide (0.56 mg/kg to10 mg/kg)/metformin (10 mg/kg to 180 mg/kg) blocked DIA. The derived theoretical effective doses for 50% of subjects (ED50) for the glibenclamide/metformin and glipizide/metformin combinations were 32.52 mg/kg and 32.42 mg/kg, respectively, and were significantly higher than the actual observed experimental ED50 values (7.57 mg/kg and 8.43 mg/kg, respectively). CONCLUSION: Pretreatment with glibenclamide, glipizide or metformin blocked DIA in a dose-dependent manner, and combining either sulfonylurea with metformin produced even greater effects. The observed ED50s for the combinations were approximately fourfold lower than the calculated additive effects. These data indicate that sulfonylureas interact to produce antagonism of DIA. Combination therapy is a common second-line treatment for patients with diabetes and metabolic syndrome, a group that experiences pain from multiple sources. The results suggest that at least some anti-inflammatory agents may not be

  13. Interaction of bilirubin and indocyanine green with the binding and conjugation of sulfobromophthalein by rat liver cytosol proteins.

    PubMed

    Davis, D R; Yeary, R A

    1980-02-01

    The interaction of bilirubin and indocyanine green with sulfobromophthalein (BSP) binding and conjugation by rat liver cytosol proteins was studied. BSP bound to cytosol proteins X, ligandin and Z and the BSP-glutathione conjugate were isolated by sephadex gel chromatography. Neither bilirubin nor indocyanine green affected the binding of BSP to ligandin and Z protein. However, indocyanine green did significantly reduce BSP conjugation in both in vitro and in vivo experiments. Diethyl maleate significantly reduced liver glutathione levels and BSP conjugation. It is suggested that indocyanine gree competitively binds at the ligandin catalytic site whereas the primary binding site for bilirubin is probably a noncatalytic site. PMID:7367753

  14. Endocrine disruption and ovarian morphometric responses in rats following exposure to tetradifon.

    PubMed

    Badraoui, Riadh; Abdelmoula, Nouha B; Feki, Nozha; Ben Nasr, Hmed; Rebai, Tarek

    2010-04-01

    We have investigated whether exposure to tetradifon causes ovary injuries, disrupts folliculogenesis in rat and whether ovary hormones (estrogen and progesterone) to be affected by this endocrine-active agent. Female rats were exposed orally to a dose of 28.9 mg/kg/day for 6 or 12 weeks. After sacrifice, ovary glands were examined for morphometric changes. The serums were used to determine levels of 17beta-estradiol and progesterone. Results showed no sign of toxicity. However, tetradifon promoted a significant increase in the percentage of atretic follicles in the 12-weeks treated rats. Number and the diameter of mature follicles (tertiary and preovulatory) were markedly diminished together with a reduction of the relative weight of ovaries. Compared with controls, the treated rats exhibited significant reduction in serum 17beta-estradiol and progesterone levels. These results suggest an endocrine disruption by tetradifon which may interfere with ovarian follicles development in rat. PMID:19800343

  15. Genotoxicity studies of methyl isocyanate in Salmonella, Drosophila, and cultured Chinese hamster ovary cells

    SciTech Connect

    Mason, J.M.; Zeiger, E.; Haworth, S.; Ivett, J.; Valencia, R.

    1987-01-01

    The genotoxic effects of methyl isocyanate (MIC) were investigated using four short-term tests: the Salmonella reversion assay (Ames test), the Drosophila sex-linked recessive lethal assay, and the sister chromatic exchange (SCE) and chromosomal aberration assays in cultured Chinese hamster ovary (CHO) cells. No evidence was found for the induction of mutations in either Salmonella or Drosophila. MIC did, however, induce SCEs and chromosomal aberrations in CHO cells both in the presence and absence of Aroclor-induced rat liver S-9.

  16. Mephedrone interactions with cocaine: prior exposure to ‘bath salt’ constituent enhances cocaine-induced locomotor activation in rats

    PubMed Central

    Gregg, Ryan A.; Tallarida, Christopher S.; Reitz, Allen B.; Rawls, Scott M.

    2014-01-01

    Concurrent use of mephedrone (4-methylmethcathinone) (MEPH) and established drugs of abuse is now commonplace, but knowledge about interactions between these drugs is sparse. The present study was designed to test the hypothesis that prior MEPH exposure enhances the locomotor-stimulant effects of cocaine and methamphetamine (METH). For cocaine experiments, rats pretreated with saline, cocaine (15 mg/kg), or MEPH (15 mg/kg) for 5 days were injected with cocaine after 10 days of drug absence. For METH experiments, rats pretreated with saline, METH (2 mg/kg), or MEPH (15 mg/kg) were injected with METH after 10 days of drug absence. Cocaine challenge produced greater locomotor activity following pretreatment with cocaine or MEPH than following pretreatment with saline. METH challenge produced greater locomotor activity following METH pretreatment than following saline pretreatment; however, locomotor activity in rats pretreated with MEPH or saline and then challenged with METH was not significantly different. The locomotor response to MEPH (15 mg/kg) was not significantly affected by pretreatment with cocaine (15 mg/kg) or METH (0.5, 2 mg/kg). The present demonstration that cocaine-induced locomotor activation is enhanced by prior MEPH exposure suggests that MEPH cross-sensitizes to cocaine and increases cocaine efficacy. Interestingly, MEPH cross-sensitization was not bi-directional and did not extend to METH, suggesting the phenomenon is sensitive to specific psychostimulants. PMID:24126218

  17. Mephedrone interactions with cocaine: prior exposure to the 'bath salt' constituent enhances cocaine-induced locomotor activation in rats.

    PubMed

    Gregg, Ryan A; Tallarida, Christopher S; Reitz, Allen B; Rawls, Scott M

    2013-12-01

    Concurrent use of mephedrone (4-methylmethcathinone; MEPH) and established drugs of abuse is now commonplace, but knowledge about interactions between these drugs is sparse. The present study was designed to test the hypothesis that prior MEPH exposure enhances the locomotor-stimulant effects of cocaine and methamphetamine (METH). For cocaine experiments, rats pretreated with saline, cocaine (15 mg/kg), or MEPH (15 mg/kg) for 5 days were injected with cocaine after 10 days of drug absence. For METH experiments, rats pretreated with saline, METH (2 mg/kg), or MEPH (15 mg/kg) were injected with METH after 10 days of drug absence. Cocaine challenge produced greater locomotor activity after pretreatment with cocaine or MEPH than after pretreatment with saline. METH challenge produced greater locomotor activity after METH pretreatment than after saline pretreatment; however, locomotor activity in rats pretreated with MEPH or saline and then challenged with METH was not significantly different. The locomotor response to MEPH (15 mg/kg) was not significantly affected by pretreatment with cocaine (15 mg/kg) or METH (0.5, 2 mg/kg). The present demonstration that cocaine-induced locomotor activation is enhanced by prior MEPH exposure suggests that MEPH cross-sensitizes to cocaine and increases cocaine efficacy. Interestingly, MEPH cross-sensitization was not bidirectional and did not extend to METH, suggesting that the phenomenon is sensitive to specific psychostimulants. PMID:24126218

  18. Genetic interaction between hyperglycemic QTLs is manifested under a high calorie diet in OLETF-derived congenic rats.

    PubMed

    Fukumura, Tomoe; Kose, Hiroyuki; Takeda, Chiyo; Kurita, Yuko; Ochiai, Kazuhiko; Yamada, Takahisa; Matsumoto, Kozo

    2011-01-01

    The condition of hyperglycemia results from multiple genetic and environmental factors. In recent years much progress has been made with regards to the search for candidate genes involved in the expression of various common diseases including type 2 diabetes. However less is known about the specific genetic and environmental connections that are important for the development of the disease. In the present study, we used hyperglycemic congenic rats to address this issue. When given a normal diet, two hyperglycemic QTLs (quantitative trait locus), Nidd2/of and Nidd10/of, showed mild obesity and/or increased blood glucose in the oral glucose tolerance test. In a double congenic strain possessing both loci, these indices were not significantly different from those of either single congenic strain. In contrast, the double congenic strain fed a high-calorie diet showed significantly greater body weight than the single congenic strains or normoglycemic control rats. Although postprandial glucose levels of the double congenic rat were not further aggravated even on the high fat diet, it was notable that the postprandial insulin levels were drastically elevated. From these results, we constructed a novel model animal especially for the study of prediabetic hyperinsulemia, in which two QTLs and an additional dietary condition are involved. This may help to shed light on the genetic basis and gene-to-diet interaction during the early stage of type 2 diabetes. PMID:21512267

  19. Inhibition of Ovarian KIT Phosphorylation by the Ovotoxicant 4-Vinylcyclohexene Diepoxide in Rats1

    PubMed Central

    Mark-Kappeler, Connie J.; Sen, Nivedita; Lukefahr, Ashley; McKee, Laurel; Sipes, I. Glenn; Konhilas, John; Hoyer, Patricia B.

    2011-01-01

    In vitro exposure of Postnatal Day 4 (PND4) rat ovaries to the occupational chemical 4-vinylcyclohexene diepoxide (VCD) destroys specifically primordial and primary follicles via acceleration of atresia. Because oocyte-expressed c-kit (KIT) plays a critical role in follicle survival and activation, a direct interaction of VCD with KIT as its mechanism of ovotoxicity was investigated. PND4 rat ovaries were cultured with and without VCD (30 μM) for 2 days. When assessed by Western analysis or mobility shift detection, phosphorylated KIT (pKIT) was decreased (P < 0.05) by VCD exposure, while total KIT protein was unaffected. Anti-mouse KIT2 (ACK2) antibody binds KIT and blocks its signaling pathways, whereas anti-mouse KIT 4 (ACK4) antibody binds KIT but does not block its activity. PND4 rat ovaries were incubated for 2 days with and without VCD with and without ACK2 (80 μg/ml) or ACK4 (80 μg/ml). ACK2 decreased pKIT; however, ACK4 had no effect. Conversely, ACK2 did not affect a VCD-induced decrease in pKIT, whereas ACK4 further reduced it. Because ACK2 and ACK4 (known to directly bind KIT) affect VCD responses, these results support the fact that VCD interacts directly with KIT. The effect of these antibodies on VCD-induced follicle loss was measured after 8 days of incubation. ACK2 further reduced (P < 0.05) VCD-induced follicle loss, whereas ACK4 did not affect it. These findings demonstrate that VCD induces ovotoxicity by direct inhibition of KIT autophosphorylation of the oocyte. The data also further support the vital function of KIT and its signaling pathway in primordial follicle survival and activation, as well as its role in VCD-induced ovotoxicity. PMID:21677306

  20. Inhibition of ovarian KIT phosphorylation by the ovotoxicant 4-vinylcyclohexene diepoxide in rats.

    PubMed

    Mark-Kappeler, Connie J; Sen, Nivedita; Lukefahr, Ashley; McKee, Laurel; Sipes, I Glenn; Konhilas, John; Hoyer, Patricia B

    2011-10-01

    In vitro exposure of Postnatal Day 4 (PND4) rat ovaries to the occupational chemical 4-vinylcyclohexene diepoxide (VCD) destroys specifically primordial and primary follicles via acceleration of atresia. Because oocyte-expressed c-kit (KIT) plays a critical role in follicle survival and activation, a direct interaction of VCD with KIT as its mechanism of ovotoxicity was investigated. PND4 rat ovaries were cultured with and without VCD (30 μM) for 2 days. When assessed by Western analysis or mobility shift detection, phosphorylated KIT (pKIT) was decreased (P < 0.05) by VCD exposure, while total KIT protein was unaffected. Anti-mouse KIT2 (ACK2) antibody binds KIT and blocks its signaling pathways, whereas anti-mouse KIT 4 (ACK4) antibody binds KIT but does not block its activity. PND4 rat ovaries were incubated for 2 days with and without VCD with and without ACK2 (80 μg/ml) or ACK4 (80 μg/ml). ACK2 decreased pKIT; however, ACK4 had no effect. Conversely, ACK2 did not affect a VCD-induced decrease in pKIT, whereas ACK4 further reduced it. Because ACK2 and ACK4 (known to directly bind KIT) affect VCD responses, these results support the fact that VCD interacts directly with KIT. The effect of these antibodies on VCD-induced follicle loss was measured after 8 days of incubation. ACK2 further reduced (P < 0.05) VCD-induced follicle loss, whereas ACK4 did not affect it. These findings demonstrate that VCD induces ovotoxicity by direct inhibition of KIT autophosphorylation of the oocyte. The data also further support the vital function of KIT and its signaling pathway in primordial follicle survival and activation, as well as its role in VCD-induced ovotoxicity. PMID:21677306

  1. Neurotensin effect on dopamine release and calcium transport in rat striatum: interactions with diphenylalkylamine calcium antagonists.

    PubMed

    Battaini, F; Govoni, S; Di Giovine, S; Trabucchi, M

    1986-03-01

    The release of dopamine was investigated in rat striatal slices exposed in vitro to neurotensin. This peptide increased basal and K+-evoked dopamine release. Moreover neurotensin antagonized the flunarizine-induced inhibition of K+-stimulated dopamine release. The K+-evoked 45Ca2+ accumulation was also inhibited by flunarizine. This effect was antagonized by neurotensin. The results suggest that dopamine release in rat striatum is regulated by different molecular events also of peptidergic nature having as possible mechanism of action an influence on calcium ion movements. PMID:3713871

  2. Surgical transposition of the ovaries: Imaging findings in 14 patients

    SciTech Connect

    Kier, R.; Chambers, S.K. )

    1989-11-01

    Pelvic radiation therapy for cervical or vaginal cancer often leads to ovarian failure. To remove the ovaries from the radiation portal and preserve their function, they can be transposed to the lateral abdomen. Serial imaging studies in 14 patients who had undergone ovarian transposition (five bilateral, nine unilateral) were reviewed. Images obtained included 32 CT scans, 20 sonograms, and one MR image. Most transposed ovaries were located along the paracolic gutters near the iliac crests, creating an extrinsic mass effect on adjacent bowel. Detection of surgical clips on the ovary on CT scans allowed confident recognition of all 19 transposed ovaries. Cysts in the transposed ovaries, noted on most imaging studies, did not correlate with complications of pain or hormonal dysfunction. In one case, a large physiologic cyst in a transposed ovary distorted the cecum and was mistaken for a mucocele of the appendix. In another case, a large ovarian cyst was thought to be tumor recurrence or a lymphocele. These findings indicate that although the transposed ovaries can be recognized on CT scans by the surgical clips attached to the ovaries, the appearance of the ovary does not predict reliably the development of complications.

  3. Melatonin inhibits cholangiocyte hyperplasia in cholestatic rats by interaction with MT1 but not MT2 melatonin receptors.

    PubMed

    Renzi, Anastasia; Glaser, Shannon; Demorrow, Sharon; Mancinelli, Romina; Meng, Fanyin; Franchitto, Antonio; Venter, Julie; White, Mellanie; Francis, Heather; Han, Yuyan; Alvaro, Domenico; Gaudio, Eugenio; Carpino, Guido; Ueno, Yoshiyuki; Onori, Paolo; Alpini, Gianfranco

    2011-10-01

    In bile duct-ligated (BDL) rats, large cholangiocytes proliferate by activation of cAMP-dependent signaling. Melatonin, which is secreted from pineal gland as well as extrapineal tissues, regulates cell mitosis by interacting with melatonin receptors (MT1 and MT2) modulating cAMP and clock genes. In the liver, melatonin suppresses oxidative damage and ameliorates fibrosis. No information exists regarding the role of melatonin in the regulation of biliary hyperplasia. We evaluated the mechanisms of action by which melatonin regulates the growth of cholangiocytes. In normal and BDL rats, we determined the hepatic distribution of MT1, MT2, and the clock genes, CLOCK, BMAL1, CRY1, and PER1. Normal and BDL (immediately after BDL) rats were treated in vivo with melatonin before evaluating 1) serum levels of melatonin, bilirubin, and transaminases; 2) intrahepatic bile duct mass (IBDM) in liver sections; and 3) the expression of MT1 and MT2, clock genes, and PKA phosphorylation. In vitro, large cholangiocytes were stimulated with melatonin in the absence/presence of luzindole (MT1/MT2 antagonist) and 4-phenyl-2-propionamidotetralin (MT2 antagonist) before evaluating cell proliferation, cAMP levels, and PKA phosphorylation. Cholangiocytes express MT1 and MT2, CLOCK, BMAL1, CRY1, and PER1 that were all upregulated following BDL. Administration of melatonin to BDL rats decreased IBDM, serum bilirubin and transaminases levels, the expression of all clock genes, cAMP levels, and PKA phosphorylation in cholangiocytes. In vitro, melatonin decreased the proliferation, cAMP levels, and PKA phosphorylation, decreases that were blocked by luzindole. Melatonin may be important in the management of biliary hyperplasia in human cholangiopathies. PMID:21757639

  4. Interaction of physical training and chronic nitroglycerin treatment on blood pressure and plasma oxidant/antioxidant systems in rats.

    PubMed

    Husain, Kazim; Somani, Satu M; Boley, Theresa M; Hazelrigg, Stephen R

    2003-05-01

    Many individuals with cardiovascular diseases undergo periodic physical conditioning with or without medication. Therefore, this study investigated the interaction of exercise training and chronic nitroglycerin treatment on blood pressure (BP) and alterations in nitric oxide (NO), glutathione (GSH), antioxidant enzyme activities and lipid peroxidation in rats. Fisher 344 rats were divided into four groups: (1) sedentary control, (2) exercise training for 8 weeks, (3) nitroglycerin (15 mg/kg, s.c. for 8 weeks) and (4) training + nitroglycerin for 8 weeks. BP, heart rate (HR) and respiratory exchange ratio (RER) were monitored weekly for 8 weeks using tail-cuff method and oxygen/carbon dioxide analyzer, respectively. The animals were sacrificed 24 h after last treatments and plasma isolated and analyzed using HPLC, ELISA and UV-VIS spectrophotometric techniques. The results show that exercise conditioning significantly enhanced NO production (p < 0.001), GSH levels (p < 0.001), GSH/GSSG ratio (p < 0.05) and the up-regulation of the activities of catalase (CAT) (p < 0.05), glutathione peroxidase (GSH-Px) (p < 0.001), and glutathione reductase (GR) (p < 0.05), and depression of lactate levels (p < 0.001) in the plasma of the rat. These biochemical changes were accompanied by a significant increase in RER (p < 0.001) without a significant change in BP and HR. Chronic nitroglycerin administration significantly increased NO levels (p < 0.05), GSH levels (p < 0.001), superoxide dismutase (SOD) activity (p < 0.05), GST activity (p < 0.05), and decreased MDA levels (p < 0.05). These biochemical changes were accompanied by a significant decrease in BP (p < 0.05) and without any significant changes in HR and RER. Interaction of exercise training and chronic nitroglycerin treatment resulted in normalization of plasma NO, MDA, lactate levels, and CAT activity. The combination of exercise and nitroglycerin significantly enhanced GSH levels (p < 0.05), and the up-regulation of SOD

  5. Cellular and molecular mechanisms of pentoxifylline's beneficial effects in experimental polycystic ovary.

    PubMed

    Rezvanfar, Mohammad A; Saadat, Sepideh; Shojaei Saadi, Habib A; Mansoori, Parisa; Saeedi, Sarah; Gooshe, Maziar; Baeeri, Maryam; Abdollahi, Mohammad

    2015-04-01

    Chronic low-grade inflammation and oxidative stress (OS) appear to be two main pathways involved in the pathogenesis of polycystic ovary (PCO) syndrome. Therefore, targeting these pathways by means of anticytokine and antioxidant agents might be a therapeutic alternative approach to the current treatments of PCO syndrome. In this study, we investigated the protective effects of pentoxifylline (PTX), a drug with antioxidant and anti-tumor necrosis factor alpha (TNF-α) properties, in hyperandrogenism-induced PCO rats. The inflammatory and OS responses and their connections with ovarian functionality in induced PCO rats were investigated through ovarian histopathologic examination and a series of biochemical measurements including serum estradiol, progesterone, testosterone, insulin, and TNF-α, ovarian and serum lipid peroxidation, total antioxidant power, and reactive oxygen species. Experimental PCO was induced in rats by oral administration of letrozole (1 mg/kg body weight) for 21 consecutive days. In a different group, PTX was administrated orally (50 mg/kg/d) for 21 days simultaneous with letrozole to assess its potential protective effects. The letrozole-induced PCOs were characterized by irregular cycles, high incidence of subcapsular ovarian cysts with diminished or scant granulosa cell layers, increased number of atretic preantral and antral follicles, and absence of CL. In addition, the letrozole-induced PCO rats exhibited notable increase in lipid peroxidation and reactive oxygen species of serum and ovary, serum testosterone, insulin, and TNF-α and significant decline in total antioxidant power, serum estradiol, and serum progesterone. Our results indicated that all the identified pathologic parameters and biochemical characteristics in letrozole-induced PCO rats in this study were preserved close to normal levels by simultaneous PTX treatments. Present results demonstrate that there is a direct connection between ovarian dysfunction and increased

  6. TOXIC INTERACTIONS BETWEEN CARBON TETRACHLORIDE AND CHLOROFORM IN CULTURED RAT HEPATOCYTES

    EPA Science Inventory

    Primary cultures of adult rat hepatocytes were incubated (1.5-16 hr) with various concentrations of CC14 (<0.5 mM) and/or CHCl3 (<2.5 mM). gent dependent alterations in hepatocyte functions were assessed by measuring (1) [3H]choline incorporation into phosphatidylcholine (endopla...

  7. Pharmacokinetic characteristics of N7-substituted theophylline derivatives and their interaction with quinolone in rats.

    PubMed

    Hasegawa, T; Nadai, M; Apichartpichean, R; Muraoka, I; Nabeshima, T; Takagi, K

    1991-10-01

    Disposition of diprophylline (DPP) and proxyphylline (PXP) and the effect of enoxacin on their disposition were investigated in rats. Concentrations of the two drugs in plasma and urine were measured by HPLC. The pharmacokinetic parameters of the two drugs were estimated by model-independent methods. Although the chemical structures of the two drugs are very similar, remarkable differences in the disposition of the two drugs were observed. Total body clearance (CLT) of DPP was 1.77 L/h/kg, which was sevenfold greater than that of PXP (0.26 L/h/kg). Diprophylline was excreted in an almost completely unchanged form in the urine, but only 50% of PXP was excreted. However, no binding of either drug to proteins in rat plasma was observed. The DPP renal clearance (CLR) was 1.75 L/h/kg, approximately 13-fold the CLR for PXP (0.13 L/h/kg) and sevenfold the rat glomerular filtration rate. This study indicates that in rats, DPP is mainly excreted by active tubular secretion and that renal tubular reabsorption contributes to renal excretion of PXP with glomerular filtration. No significant changes in any pharmacokinetic parameters of the two drugs were observed when they were coadministered with enoxacin, compared with the drug administered alone, suggesting that enoxacin had no effect on the pharmacokinetics of either drug. PMID:1664467

  8. INTERACTION OF AMBIENT TEMPERATURE AND MICROWAVE POWER DENSITY ON SCHEDULE-CONTROLLED BEHAVIOR IN THE RAT

    EPA Science Inventory

    Most guidelines of microwave exposure do not explicitly address effects of ambient temperature. The experiment revealed that ambient temperature potentiates the behavioral effects of intensity of irradiation. Sixty-four adult male Long-Evans rats were trained to insert their head...

  9. Dietary selenium (Se) and copper (Cu) interact to affect homocysteine metabolism in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previously we reported that both Se deficiency (SeD) and Cu deficiency (CuD) decreased plasma homocysteine (pHcys) and increased plasma glutathione (pGSH) in rats. We also showed that the catalytic subunit of glutamate-cysteine ligase (Gclc), which catalyzes the rate limiting step in glutathione bio...

  10. Impact Depth and the Interaction with Impact Speed Affect the Severity of Contusion Spinal Cord Injury in Rats

    PubMed Central

    Lam, Cameron J.; Assinck, Peggy; Liu, Jie; Tetzlaff, Wolfram

    2014-01-01

    Abstract Spinal cord injury (SCI) biomechanics suggest that the mechanical factors of impact depth and speed affect the severity of contusion injury, but their interaction is not well understood. The primary aim of this work was to examine both the individual and combined effects of impact depth and speed in contusion SCI on the cervical spinal cord. Spinal cord contusions between C5 and C6 were produced in anesthetized rats at impact speeds of 8, 80, or 800 mm/s with displacements of 0.9 or 1.5 mm (n=8/group). After 7 days postinjury, rats were assessed for open-field behavior, euthanized, and spinal cords were harvested. Spinal cord tissue sections were stained for demyelination (myelin-based protein) and tissue sparing (Luxol fast blue). In parallel, a finite element model of rat spinal cord was used to examine the resulting maximum principal strain in the spinal cord during impact. Increasing impact depth from 0.9 to 1.5 mm reduced open-field scores (p<0.01) above 80 mm/s, reduced gray (GM) and white matter (WM) sparing (p<0.01), and increased the amount of demyelination (p<0.01). Increasing impact speed showed similar results at the 1.5-mm impact depth, but not the 0.9-mm impact depth. Linear correlation analysis with finite element analysis strain showed correlations (p<0.001) with nerve fiber damage in the ventral (R2=0.86) and lateral (R2=0.74) regions of the spinal cord and with WM (R2=0.90) and GM (R2=0.76) sparing. The results demonstrate that impact depth is more important in determining the severity of SCI and that threshold interactions exist between impact depth and speed. PMID:24945364

  11. Isolation and co-culture of rat parenchymal and non-parenchymal liver cells to evaluate cellular interactions and response

    PubMed Central

    Bale, Shyam Sundhar; Geerts, Sharon; Jindal, Rohit; Yarmush, Martin L.

    2016-01-01

    The liver is a central organ in the human body, and first line of defense between host and external environment. Liver response to any external perturbation is a collective reaction of resident liver cells. Most of the current in vitro liver models focus on hepatocytes, the primary metabolic component, omitting interactions and cues from surrounding environment and non-parenchymal cells (NPCs). Recent studies suggest that contributions of NPCs are vital, particularly in disease conditions, and outcomes of drugs and their metabolites. Along with hepatocytes, NPCs–Kupffer (KC), sinusoidal endothelial (LSEC) and stellate cells (SC) are major cellular components of the liver. Incorporation of primary cells in in vitro liver platforms is essential to emulate the functions of the liver, and its overall response. Herein, we isolate individual NPC cell fractions from rat livers and co-culture them in a transwell format incorporating primary rat hepatocytes with LSECs, SCs, and KCs. Our results indicate that the presence and contributions of multiple cells within the co-culture capture the interactions between hepatocytes and NPC, and modulates the responses to inflammatory stimulus such as LPS. The isolation and co-culture methods could provide a stable platform for creating in vitro liver models that provide defined functionality beyond hepatocytes alone. PMID:27142224

  12. Isolation and co-culture of rat parenchymal and non-parenchymal liver cells to evaluate cellular interactions and response.

    PubMed

    Bale, Shyam Sundhar; Geerts, Sharon; Jindal, Rohit; Yarmush, Martin L

    2016-01-01

    The liver is a central organ in the human body, and first line of defense between host and external environment. Liver response to any external perturbation is a collective reaction of resident liver cells. Most of the current in vitro liver models focus on hepatocytes, the primary metabolic component, omitting interactions and cues from surrounding environment and non-parenchymal cells (NPCs). Recent studies suggest that contributions of NPCs are vital, particularly in disease conditions, and outcomes of drugs and their metabolites. Along with hepatocytes, NPCs-Kupffer (KC), sinusoidal endothelial (LSEC) and stellate cells (SC) are major cellular components of the liver. Incorporation of primary cells in in vitro liver platforms is essential to emulate the functions of the liver, and its overall response. Herein, we isolate individual NPC cell fractions from rat livers and co-culture them in a transwell format incorporating primary rat hepatocytes with LSECs, SCs, and KCs. Our results indicate that the presence and contributions of multiple cells within the co-culture capture the interactions between hepatocytes and NPC, and modulates the responses to inflammatory stimulus such as LPS. The isolation and co-culture methods could provide a stable platform for creating in vitro liver models that provide defined functionality beyond hepatocytes alone. PMID:27142224

  13. Interaction of pinaverium (a quaternary ammonium compound) with 1,4-dihydropyridine binding sites in rat ileum smooth muscle.

    PubMed

    Feron, O; Wibo, M; Christen, M O; Godfraind, T

    1992-02-01

    1. The interaction of pinaverium bromide, a quaternary ammonium compound, with binding sites for (L-type) calcium channel blockers was investigated in rat ileum smooth muscle. 2. Pinaverium inhibited [3H]-(+)-PN200-110 ([3H]-(+)-isradipine) specific binding to tissue homogenates incompletely (Ki 0.38 microM; maximal inhibition 80%). In contrast, binding to single cell preparations (obtained by collagenase treatment) and to saponin-treated homogenates was completely inhibited. These data are compatible with the view that, in untreated homogenates, 20% of [3H]-(+)-isradipine binding sites are not accessible to pinaverium because it is associated with sealed inside-out vesicles. 3. Pinaverium bromide increased the apparent KD of [3H]-(+)-isradipine binding to saponin-treated homogenates but did not significantly affect the Bmax value. Moreover, the dissociation rate constant of [3H]-(+)-isradipine binding was not changed by pinaverium. These data suggest that pinaverium interacts with the dihydropyridine binding site in a competitive manner. However, in contrast to uncharged dihydropyridine calcium antagonists, pinaverium inhibited, rather than stimulated, [3H]-diltiazem binding to rat brain membranes (at 30-37 degrees C). 4. Although Bmax values of [3H]-(+)-isradipine were similar in homogenates prepared from tissue and cells (collagenase-treated), the KD value was significantly higher in cell homogenates (166 vs 95 pM). Similarly, the Ki value of pinaverium was higher in cell preparations than in tissue homogenates (0.77 vs 0.38 microM). Thus, collagenase can significantly modify the dihydropyridine recognition site.5. The competitive interaction of pinaverium, a permanently charged drug, with [3H]-(+)-isradipine bound to intact cells and its absence of interaction with [3H]-(+)-isradipine bound to sealed inside-out vesicles imply that the dihydropyridine receptor lies near the external surface of the plasma membrane. PMID:1313732

  14. Rat and human colonic mucins bind to and inhibit adherence lectin of Entamoeba histolytica.

    PubMed Central

    Chadee, K; Petri, W A; Innes, D J; Ravdin, J I

    1987-01-01

    Establishment of adherence by Entamoeba histolytica is mediated by a 170-kD Gal/GalNAc inhibitable lectin and is required for cytolysis and phagocytosis of mammalian target cells. We studied the biochemical mechanisms of the in vitro interaction between rat and human colonic mucins and axenic E. histolytica trophozoites. Crude mucus prevented amebic adherence to Chinese hamster ovary (CHO) cells by up to 70%. Purification of the colonic mucins by Sepharose 4B chromatography, nuclease digestion, and cesium chloride gradient centrifugation resulted in a 1,000-fold enrichment of the inhibitory mucins. Purified rat mucin inhibited amebic adherence to and cytolysis of homologous rat colonic epithelial cells. Oxidation and enzymatic cleavage of rat mucin Gal and GalNAc residues completely abrogated mucin inhibition of amebic adherence. The binding of rat 125I-mucin to amebae was galactose specific, saturable, reversible, and pH dependent. A monoclonal antibody specific for the 170-kD amebic Gal/GalNAc lectin completely inhibited the binding of rat 125I-mucin. Rat mucin bound to Affigel affinity purified the amebic lectin from conditioned medium. Colonic mucin glycoproteins act as an important host defense by binding to the parasite's adherence lectin, thus preventing amebic attachment to and cytolysis of host epithelial cells. Images PMID:2890655

  15. ANDROGENS AND OPIATES: TESTOSTERONE INTERACTION WITH MORPHINE SELF-ADMINISTRATION IN MALE RATS

    PubMed Central

    Cooper, Sarah E.; Wood, Ruth I.

    2016-01-01

    Abuse of anabolic-androgenic steroids (AAS) and opioids intersect in athletics. Evidence from humans and animals suggests that AAS may act in the brain via opioidergic mechanisms, and may potentiate effects of opioids. To determine if AAS enhance motivation for opioid intake, this study treated male rats chronically for 6 weeks with high levels of testosterone (7.5 mg/kg) or vehicle s.c. and tested them for morphine self-administration under fixed (FR) and progressive ratio (PR) schedules. Initially, rats received chronic morphine infusion (16.8–50 mg/kg/day) over 7 days. Subsequently, rats were tested for morphine self-administration (3.2 mg/kg) 6h/day for 3 days under an FR1 schedule, and for 7 days under a PR 9-4 schedule. With FR1, controls self-administered more morphine (95.9±8.5 mg/kg), compared with testosterone-treated rats (63.2±7.2 mg/kg, p<0.05). Under PR, there was no effect of testosterone on morphine intake or operant responding (26.7±5.7 responses vs 30.9±5.9 responses for vehicle; n.s.). To determine if testosterone enhances morphine sedation, additional rats were treated with testosterone or vehicle and evaluated for locomotor behavior and rearing activity over 30 min in response to saline or 10 mg/kg morphine. Morphine inhibited locomotor activity and rearing; testosterone selectively reduced rearing behavior, but did not alter locomotor behavior. These results suggest that testosterone does not increase motivation for morphine. PMID:24488032

  16. Oral contraceptives in polycystic ovary syndrome.

    PubMed

    Helvaci, N; Yildiz, B O

    2014-09-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of women of reproductive age and combined oral contraceptives (OCs) are often the first-line treatment of the syndrome by improving hyperandrogenism and regulating menstrual cycles. Oral contraceptives have some cardiovascular and metabolic effects that varies among different formulations depending upon the dose and type of the both estrogen and progestin components. These cardiometabolic effects of OCs raise some concerns about their long-term use in PCOS, but available data suggest that the benefits outweigh the risks. More studies are needed to clarify the safety of long-term use of OCs in PCOS. PMID:25003228

  17. Functional and anatomical characteristics of the nerve-brown adipose interaction in the rat

    NASA Technical Reports Server (NTRS)

    Flaim, K. E.; Horowitz, J. M.; Horwitz, B. A.

    1976-01-01

    Experiments were conducted on 12 male rats to study the coupling of signals from the sympathetic nervous system to the brown adipose tissue. Analysis of electron photomicrographs revealed considerable morphological heterogeneity among the nerves entering and leaving the interscapular fat pad. In response to electrical simulation of the nerves, the temperature of the brown fat increased following a rapid but transient temperature drop. Such changes were observed only on the ipsilateral side, indicating that the innervation to the interscapular brown fat of the rat is functionally bilateral rather than diffuse. The finding that brown fat is capable of responding in a graded fashion correlates well with observations suggesting that clusters of brown adipocytes may be electrically coupled.

  18. TLR4 stimulation and corticosteroid interactively induce osteonecrosis of the femoral head in rat.

    PubMed

    Okazaki, Shunichiro; Nagoya, Satoshi; Matsumoto, Hiroshi; Mizuo, Keisuke; Shimizu, Junya; Watanabe, Satoshi; Inoue, Hiromasa; Yamashita, Toshihiko

    2016-02-01

    We previously reported that a toll-like receptor 4 signaling contributes to the development of osteonecrosis of the femoral head. Also, oxidative stress is suggested to be one of the possible pathogenesis of osteonecrosis of the femoral head. A recent study showed that toll-like receptor 4 signaling leads to oxidative stress. The aim of the present study was to evaluate whether toll-like receptor 4 stimulation and subsequent corticosteroid treatment lead to the development of osteonecrosis of the femoral head in rat, and oxidative stress is associated with it. Male Wistar rats were randomly divided into four treatment groups: Saline + Saline, Saline + Methylprednisolone, Lipopolysaccharide + Saline, Lipopolysaccharide + Methylprednisolone. Osteonecrosis of the femoral head at 14 days after the treatment was observed in 1 of 10 Lipopolysaccharide + Saline, and 5 of 10 Lipopolysaccharide + Methylprednisolone treated rats. However, it was not observed at all in the Saline + Saline and Saline + Methylprednisolone treated groups. Glutathione peroxidase activity in the liver at 1 day after the treatment was significantly increased when treated with lipopolysaccharide. However, methylprednisolone treatment reduced the activity. On the other hand, glutathione peroxidase activity in the femur did not change in any intergroup. In conclusion, the present study showed that toll-like receptor 4 stimulation by lipopolysaccharide administration strengthen incidence of corticosteroid-induced osteonecrosis of the femoral head, however, concomitant oxidative stress via toll-like receptor 4 signaling may not contribute to the development of osteonecrosis of the femoral head in rats. PMID:26249756

  19. Ethopharmacological evaluation of the rat exposure test: a prey-predator interaction test.

    PubMed

    Campos, Kelciane Ferreira Caetano; Amaral, Vanessa Cristiane Santana; Rico, Javier Leonardo; Miguel, Tarciso Tadeu; Nunes-de-Souza, Ricardo Luiz

    2013-03-01

    The rat exposure test (RET) is a prey (mouse)-predator (rat) situation that activates brain defensive areas and elicits hormonal and defensive behavior in the mouse. Here, we investigated possible correlations between the spatiotemporal [time spent in protected (home chamber and tunnel) and unprotected (surface) compartments and frequency of entries into the three compartments] and ethological [e.g., duration of protected and unprotected stretched-attend postures (SAP), duration of contact with the rat's compartment] measures (Experiment 1). Secondly, we investigated the effects of systemic treatment with pro- or anti-aversive drugs on the behavior that emerged from the factor analysis (Experiment 2). The effects of chronic (21 days) imipramine and fluoxetine on defensive behavior were also investigated (Experiment 3). Exp. 1 revealed that the time in the protected compartment, protected SAP and rat contacts loaded on factor 1 (defensive behavior), while the total entries and unprotected SAP loaded on factor 2 (locomotor activity). Exp. 2 showed that alprazolam (but not diazepam) selectively changed the defensive factor. Caffeine produced a mild proaversive-like effect, whereas yohimbine only decreased locomotor activity (total entries). Fluoxetine (but not imipramine) produced a weak proaversive-like effect. 5-HT(1A)/5-HT(2) receptor ligands did not change any behavioral measure. In Exp. 3, chronic fluoxetine (but not imipramine) attenuated the defensive behavior factor without changing locomotion. Given that the defensive factor was sensitive to drugs known to attenuate (alprazolam and chronic fluoxetine) and induce (caffeine) panic attack, we suggest the RET as a useful test to assess the effects of panicolytic and panicogenic drugs. PMID:23195112

  20. Tumor necrosis factor-induced contraction of cultured rat mesangial cells: interaction with angiotensin II.

    PubMed

    Medina, J; Baud, L; Garcia Escribano, C; Gila, J A; Rodriguez Puyol, D; Rodriguez Puyol, M

    1993-08-01

    The role of tumor necrosis factor alpha in the regulation of renal function, particularly glomerular filtration rate, has not been completely defined. This study was designed to assess the intrinsic role of this cytokine on glomerular filtration rate by analyzing its short-term effect on the degree of contraction in cultured rat mesangial cells, not only directly but also in the presence of angiotensin II. Contraction was evaluated both morphologically--by measuring planar cell surface area of cultured rat mesangial cells and glomerular cross-sectional area of isolated rat glomeruli--and biochemically--by analyzing myosin light-chain phosphorylation in cells. Tumor necrosis factor alpha significantly decreased planar cell surface area in a dose-dependent and time-dependent manner, an effect completely abolished by preincubation of the cells with platelet-activating factor receptor antagonists BN 52021 and alprazolam. This effect was also observed in the presence of angiotensin II, whether tumor necrosis factor alpha was added before or after angiotensin II, increasing the reduction in planar cell surface area induced by angiotensin II in both cases. Changes in planar cell surface area were evident not only when the absolute values of this parameter were considered but also when the percentage of contracted cells (cells with a planar cell surface area reduction > 10%) was analyzed. Tumor necrosis factor alpha also induced a significant reduction of glomerular cross-sectional area in isolated rat glomeruli. The results of the morphologic studies were supported by myosin light-chain phosphorylation experiments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8340701

  1. Bicarbonate-water interactions in the rat proximal convoluted tubule. An effect of volume flux on active proton secretion

    PubMed Central

    1984-01-01

    The effect of volume absorption on bicarbonate absorption was examined in the in vivo perfused rat proximal convoluted tubule. Volume absorption was inhibited by isosmotic replacement of luminal NaCl with raffinose. In tubules perfused with 25 mM bicarbonate, as raffinose was increased from 0 to 55 to 63 mM, volume absorption decreased from 2.18 +/- 0.10 to 0.30 +/- 0.18 to -0.66 +/- 0.30 nl/mm X min, respectively, and bicarbonate absorption decreased from 131 +/- 5 to 106 +/- 8 to 91 +/- 13 pmol/mm X min, respectively. This bicarbonate-water interaction could not be attributed to dilutional changes in luminal or peritubular bulk phase bicarbonate concentrations. Inhibition of active proton secretion by acetazolamide abolished the effect of volume flow on bicarbonate absorption, which implies that the bicarbonate reflection coefficient is close to 1 and eliminates the possibility of solvent drag across the tight junction. When the luminal bicarbonate concentration was varied, the magnitude of the bicarbonate-water interaction increased with increasing luminal bicarbonate concentration. The largest interaction occurred at high luminal bicarbonate concentrations, where the rate of proton secretion has been previously shown to be independent of luminal bicarbonate concentration and pH. The results thus suggest that a peritubular and/or cellular compartment exists that limits bicarbonate diffusion, and where pH changes secondary to bicarbonate-water interactions (solute polarization) alter the rate of active proton secretion. PMID:6096481

  2. Gonadotropin-releasing hormone in the ovary.

    PubMed

    Metallinou, Chryssa; Asimakopoulos, Byron; Schröer, Andreas; Nikolettos, Nikos

    2007-12-01

    Gonadotropin-releasing hormone (GnRH) plays a pivotal role in the physiology of reproduction in mammals. GnRH acts by binding to the GnRH receptor (GnRHR). In humans, only 1 conventional GnRH receptor subtype (type I GnRH receptor) has been found. In the human genome, 2 forms of GnRH have been identified, GnRH-I (mammal GnRH) and GnRH-II (chicken GnRH II). Both forms and their common receptor are expressed, apart from the hypothalamus, in various compartments of the human ovary. Gonadal steroids, gonadotropins, and GnRH itself controls the regulation of the GnRH/GnRHR system gene expression in the human ovary. The 2 types of GnRH acting paracrinally/autocrinally influence ovarian steroidogenesis, decrease the proliferation, and induce apoptosis of ovarian cells. In this review, the biology of GnRH/GnRHR system in humans, the potential roles of GnRH, and the direct effects of GnRH analogues in ovarian cells are discussed. PMID:18089592

  3. Polycystic Ovaries Associated with Congenital Adrenal Hyperplasia

    PubMed Central

    Lucis, O. J.; Hobkirk, R.; Hollenberg, C. H.; MacDonald, S. A.; Blahey, P.

    1966-01-01

    Polycystic ovaries were found in a 16-year-old female with congenital absence of vagina, male-like external genitalia, and congenital adrenal hyperplasia. Masculinization was sufficiently severe to cause the patient to be reared as a male. Biochemical studies of ovarian tissue revealed hyperactivity and an imbalance of enzyme systems concerned with steroid-hormone biosynthesis, which led to production of large amounts of androgens. The pathway towards estrogens was preserved but less efficient than normal. Urinary steroid metabolites before and after hysterectomy and bilateral salpingo-oophorectomy revealed an absence of Porter-Silber chromogens and tetrahydrocortisone. Excretion of aldosterone was normal and that of corticosterone slightly higher than normal. The patterns of urinary 17-ketosteroids, pregnanediol, pregnanetriol and pregnanetriolone were similar to those commonly seen in congenital adrenal hyperplasia with steroid 21-hydroxylase deficiency. Urinary estrogens after panhysterectomy were low, being in the post-menopausal range. The pathogenesis of polycystic ovaries and their possible contribution to masculinization are discussed. ImagesFig. 1Fig. 2Fig. 3 PMID:5901591

  4. Polycystic ovary syndrome and prolactinoma association.

    PubMed

    Yavasoglu, Irfan; Kucuk, Mert; Coskun, Adil; Guney, Engin; Kadikoylu, Gurhan; Bolaman, Zahit

    2009-01-01

    Hyperprolactinemia is the most common pituitary hormone hypersecretion syndrome in both men and women. Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting 5%-10% of reproductive age women. Here, we present a patient with irregular menses, obesity, hirsutism and infertility, and hyperprolactinemia who was diagnosed as PCOS and prolactinoma and admitted to our clinic. Prolactinoma and PCOS association is a rare condition. This 33-year-old woman was admitted to the internal medicine outpatient clinic for irregular menses, obesity, hirsutism and infertility, and hyperprolactinemia. Her laboratory results were as follows: prolactin was 74 ng/mL (normal range:1.8-20.3 ng/mL). Pelvic ultrasonography was correlated with polycystic ovary syndrome. Pituitary MRI showed 6x8 mm microadenoma at left half. Bromocriptine was started with 1.25 mg/day and increased to 5 mg/day. After six months of bromocriptine treatment her prolactin level was normal and no adenoma was detected in pituitary MRI. PCOS and prolactinoma association should be taken into account in PCOS cases with mild hyperprolactinoma. PMID:19367058

  5. Analysis of Phagocytosis in the Drosophila Ovary.

    PubMed

    Meehan, Tracy L; Serizier, Sandy B; Kleinsorge, Sarah E; McCall, Kimberly

    2016-01-01

    Programmed cell death (PCD) is essential for health and development. Generally, the last step of PCD is clearance, or engulfment, by phagocytes. Engulfment can be broken down into five basic steps: attraction of the phagocyte, recognition of the dying cell, internalization, phagosome maturation, and acidification of the engulfed material. The Drosophila melanogaster ovary serves as an excellent model to study diverse types of PCD and engulfment by epithelial cells. Here, we describe several methods to detect and analyze multiple steps of engulfment in the Drosophila ovary: recognition, vesicle uptake, phagosome maturation, and acidification. Annexin V detects phosphatidylserine, which is flipped to the outer leaflet of the plasma membrane of apoptotic cells, serving as an "eat me" signal. Several germline markers including tral-GFP, Orb, and cleaved Dcp-1 can all be used to label the germline and visualize its uptake into engulfing follicle cells. Drosophila strains expressing GFP and mCherry protein fusions can enable a detailed analysis of phagosome maturation. LysoTracker labels highly acidified compartments, marking phagolysosomes. Together these labels can be used to mark the progression of engulfment in Drosophila follicle cells. PMID:27557574

  6. Interaction of flunarizine with sodium valproate or ethosuximide in gamahydroxybutyrate induced absence seizures in rats.

    PubMed

    Subramanyam, K; David, J; Joseph, T

    2001-10-01

    Sodium valproate(VPA), ethosuximide(ESM), 200 mg/kg ip and flunarizine (FLU) 5 or 10 mg/kg ip were first administered independently to rats in order to study their effects on behavioural and EEG aspects of spike and wave discharges (SWDs) induced by y- hydroxybutyrate (GHB,100 mg/kg ip). GHB treated rats show behavioural changes and concomitant repetitive EEG episodes of 7 to 9 Hz SWDs, mimicking human absence seizures (AS), and can be used as a pharmacological model. The number and duration of SWDs were calculated for 1 hr from the EEG and were parameters for drug evaluation. VPA and ESM at 200 mg/kg, significantly reduced SWD number and duration/hr, while FLU showed significant reduction only at 10 but not at 5 mg/kg. Combination of FLU, 10 mg/kg with either VPA or ESM showed significant reduction of SWD number and duration, suggesting an additive effect of the anti-absence agents with the calcium channel blocker, FLU, on experimental absence seizures in rats. PMID:11883524

  7. Interaction of ethanol and microwaves on the blood-brain barrier of rats

    SciTech Connect

    Neilly, J.P.; Lin, J.C.

    1986-01-01

    The combined effects of ethanol and microwaves on the permeation of Evans blue dye through the mammalian blood-brain barrier was studied in male Wistar rats. Anesthetized rats were infused through a cannula in the left femoral vein with 0.1, 0.3, 0.5 or 0.7 grams of absolute ethanol per kilogram of body mass. A control group was given 0.7 g/kg of isotonic saline. The left hemisphere of the brain was irradiated by 3.15-GHz microwave energy at 3.0 W/cm2 rms for 15 min. The rat's rectal temperature was maintained at 37.0 degrees C. Immediately after irradiation, 2% Evans blue dye in saline (2.0 ml/kg body mass) was injected through the cannula. The results show that as the quantity of alcohol was increased, the degree of staining was decreased or eliminated. The temperature of the irradiated area of the brain increased for the first 4 to 5 minutes of irradiation and then stabilized for the remainder of the irradiation period. The steady-state temperature was highest in animals receiving saline or the smallest dose of alcohol. As the quantity of alcohol was increased, the steady-state temperature was reduced. These results indicate that ethanol inhibits microwave-induced permeation of the blood-brain barrier through reduced heating of the brain.

  8. Life-threatening interaction between the root extract of Pueraria lobata and methotrexate in rats

    SciTech Connect

    Chiang, H.-M.; Fang, S.-H.; Wen, K.-C.; Hsiu, S.-L.; Tsai, Shang-Yuan; Hou, Y.-C.; Chi, Y.-C.; Lee Chao, Pei-Dawn . E-mail: pdlee@mail.cmu.edu.tw

    2005-12-15

    Isoflavone supplements are nowadays widely used as alternative for hormone replacement therapy. However, the safety remains unanswered. This study attempted to investigate the effect of Pueraria lobata root decoction (PLRD), an isoflavone-rich herb, on the pharmacokinetics of methotrexate (MTX), a bicarboxylate antimetabolite with narrow therapeutic window. Rats were orally and intravenously given methotrexate alone and coadministered with PLRD. Blood samples were withdrawn via cardiopuncture at specific time points after drug administration. Serum methotrexate concentrations were assayed by specific monoclonal fluorescence polarization immunoassay method. Pharmacokinetic parameters were calculated using noncompartment model of WINNONLIN for both oral and intravenous data of MTX. Our results showed that coadministration of 4.0 g/kg and 2.0 g/kg of PLRD significantly increased the AUC{sub 0-t} by 207.8% and 127.9%, prolonged the mean residence time (MRT) by 237.8 and 155.2%, respectively, finally resulted in surprisingly high mortalities of 57.1% and 14.3% in rats. When MTX was given intravenously, the coadministration of PLRD at 4.0 g/kg significantly increased the half-life by 53.9% and decreased the clearance by 47.9%. In conclusion, the coadministration of PLRD significantly decreased the elimination and resulted in markedly increased exposure of MTX in rats.

  9. Life-threatening interaction between the root extract of Pueraria lobata and methotrexate in rats.

    PubMed

    Chiang, Hsiu-Mei; Fang, Shih-Hua; Wen, Kuo-Ching; Hsiu, Su-Lan; Tsai, Shang-Yuan; Hou, Yu-Chi; Chi, Ying-Chang; Chao, Pei-Dawn Lee

    2005-12-15

    Isoflavone supplements are nowadays widely used as alternative for hormone replacement therapy. However, the safety remains unanswered. This study attempted to investigate the effect of Pueraria lobata root decoction (PLRD), an isoflavone-rich herb, on the pharmacokinetics of methotrexate (MTX), a bicarboxylate antimetabolite with narrow therapeutic window. Rats were orally and intravenously given methotrexate alone and coadministered with PLRD. Blood samples were withdrawn via cardiopuncture at specific time points after drug administration. Serum methotrexate concentrations were assayed by specific monoclonal fluorescence polarization immunoassay method. Pharmacokinetic parameters were calculated using noncompartment model of WINNONLIN for both oral and intravenous data of MTX. Our results showed that coadministration of 4.0 g/kg and 2.0 g/kg of PLRD significantly increased the AUC(0-t) by 207.8% and 127.9%, prolonged the mean residence time (MRT) by 237.8 and 155.2%, respectively, finally resulted in surprisingly high mortalities of 57.1% and 14.3% in rats. When MTX was given intravenously, the coadministration of PLRD at 4.0 g/kg significantly increased the half-life by 53.9% and decreased the clearance by 47.9%. In conclusion, the coadministration of PLRD significantly decreased the elimination and resulted in markedly increased exposure of MTX in rats. PMID:15936791

  10. Nicotine-induced plasma corticosterone is attenuated by social interactions in male and female adolescent rats.

    PubMed

    Pentkowski, N S; Painter, M R; Thiel, K J; Peartree, N A; Cheung, T H C; Deviche, P; Adams, M; Alba, J; Neisewander, J L

    2011-11-01

    Most smokers begin smoking during adolescence, a period during which social reward is highly influential. Initial exposure to nicotine can produce anxiogenic effects that may be influenced by social context. This study examined play behavior and plasma corticosterone following nicotine administration (0.6 mg/kg, s.c.) in both male and female adolescent (PND39) Sprague-Dawley rats in either isolate or social contexts. In blood samples collected immediately following the 15-min test session, nicotine increased plasma corticosterone relative to saline in both male and female isolate rats, but failed to do so in both males and females placed together in same-sex pairs. Nicotine also attenuated several indices of play behavior including nape attacks, pins and social contact. In isolate rats, nicotine selectively increased locomotor activity in females; however, when administered to social pairs, nicotine decreased locomotion in both sexes. These findings suggest that the presence of a social partner may decrease the initial negative, stress-activating effects of nicotine, perhaps leading to increased nicotine reward. PMID:21782841

  11. Nicotine-induced plasma corticosterone is attenuated by social interactions in male and female adolescent rats

    PubMed Central

    Pentkowski, N.S.; Painter, M.R.; Thiel, K.J.; Peartree, N.A.; Cheung, T.H.C.; Deviche, P.; Adams, M.; Alba, J.; Neisewander, J.L.

    2011-01-01

    Most smokers begin smoking during adolescence, a period during which social reward is highly influential. Initial exposure to nicotine can produce anxiogenic effects that may be influenced by social context. This study examined play behavior and plasma corticosterone following nicotine administration (0.6 mg/kg, s.c.) in both male and female adolescent (PND39) Sprague-Dawley rats in either isolate or social contexts. In blood samples collected immediately following the 15-min test session, nicotine increased plasma corticosterone relative to saline in both male and female isolate rats, but failed to do so in both males and females placed together in same-sex pairs. Nicotine also attenuated several indices of play behavior including nape attacks, pins and social contact. In isolate rats, nicotine selectively increased locomotor activity in females; however, when administered to social pairs, nicotine decreased locomotion in both sexes. These findings suggest that the presence of a social partner may decrease the initial negative, stress-activating effects of nicotine, perhaps leading to increased nicotine reward. PMID:21782841

  12. Interactions between chemokine and mu-opioid receptors: Anatomical findings and electrophysiological studies in the rat periaqueductal grey

    PubMed Central

    Heinisch, Silke; Palma, Jonathan; Kirby, Lynn G.

    2010-01-01

    Opioids have immunomodulatory functions and may alter susceptibility to immune disorders. Behavioral studies also indicate that chemokines, molecules expressed by immune cells, block opioid induced analgesia in the periaqueductal grey (PAG). Bi-directional heterologous desensitization of opioid and chemokine receptors has been described in cell systems. We report the anatomical and functional interactions of chemokine receptors with the mu-opioid receptor (MOR) in the rat brain. The chemokine receptors, CXCR4 and CX3CR1, as well as their chemokine substrates, CXCL12 and CX3CL1, are widely expressed in the central nervous system (CNS). Immunohistochemical techniques were utilized to investigate MOR-CXCR4 and MOR-CX3CR1 receptor colocalization in multiple brain areas. Our results demonstrate co-expression of these receptors on individual neurons in several regions including cingulate cortex, hippocampus and PAG, suggesting functional receptor interactions. Whole-cell patch-clamp recordings of PAG neurons in a rat brain slice preparation were used to examine morphine or chemokine (CXCL12, CX3CL1) effects alone or in combination on neuronal membrane properties. Morphine (10 µM) hyperpolarized and reduced input resistance of PAG neurons. CXCL12 and CX3CL1 (10 nM) had no impact on either parameter. In the presence of CXCL12, morphine’s electrophysiological effects were blocked in all neurons, whereas with CX3CL1, morphine’s effects were blocked in 57% of neurons. The data provide electrophysiological evidence for MOR-CXCR4 and MOR-CX3CR1 heterologous desensitization in the PAG at the single cell level. These interactions may contribute to the limited utility of opioid analgesics for inflammatory pain treatment and supports chemokines as neuromodulators. PMID:20974247

  13. A comprehensive transcriptomic analysis of infant and adult mouse ovary.

    PubMed

    Pan, Linlin; Gong, Wei; Zhou, Yuanyuan; Li, Xiaonuan; Yu, Jun; Hu, Songnian

    2014-10-01

    Ovary development is a complex process involving numerous genes. A well-developed ovary is essential for females to keep fertility and reproduce offspring. In order to gain a better insight into the molecular mechanisms related to the process of mammalian ovary development, we performed a comparative transcriptomic analysis on ovaries isolated from infant and adult mice by using next-generation sequencing technology (SOLiD). We identified 15,454 and 16,646 transcriptionally active genes at the infant and adult stage, respectively. Among these genes, we also identified 7021 differentially expressed genes. Our analysis suggests that, in general, the adult ovary has a higher level of transcriptomic activity. However, it appears that genes related to primordial follicle development, such as those encoding Figla and Nobox, are more active in the infant ovary, whereas expression of genes vital for follicle development, such as Gdf9, Bmp4 and Bmp15, is upregulated in the adult. These data suggest a dynamic shift in gene expression during ovary development and it is apparent that these changes function to facilitate follicle maturation, when additional functional gene studies are considered. Furthermore, our investigation has also revealed several important functional pathways, such as apoptosis, MAPK and steroid biosynthesis, that appear to be much more active in the adult ovary compared to those of the infant. These findings will provide a solid foundation for future studies on ovary development in mice and other mammals and help to expand our understanding of the complex molecular and cellular events that occur during postnatal ovary development. PMID:25251848

  14. Interactive toxicity of inorganic mercury and trichloroethylene in rat and human proximal tubules: Effects on apoptosis, necrosis, and glutathione status

    SciTech Connect

    Lash, Lawrence H. . E-mail: l.h.lash@wayne.edu; Putt, David A.; Hueni, Sarah E.; Payton, Scott G.; Zwickl, Joshua

    2007-06-15

    Simultaneous or prior exposure to one chemical may alter the concurrent or subsequent response to another chemical, often in unexpected ways. This is particularly true when the two chemicals share common mechanisms of action. The present study uses the paradigm of prior exposure to study the interactive toxicity between inorganic mercury (Hg{sup 2+}) and trichloroethylene (TRI) or its metabolite S-(1,2-dichlorovinyl)-L-cysteine (DCVC) in rat and human proximal tubule. Pretreatment of rats with a subtoxic dose of Hg{sup 2+} increased expression of glutathione S-transferase-{alpha}1 (GST{alpha}1) but decreased expression of GST{alpha}2, increased activities of several GSH-dependent enzymes, and increased GSH conjugation of TRI. Primary cultures of rat proximal tubular (rPT) cells exhibited both necrosis and apoptosis after incubation with Hg{sup 2+}. Pretreatment of human proximal tubular (hPT) cells with Hg{sup 2+} caused little or no changes in GST expression or activities of GSH-dependent enzymes, decreased apoptosis induced by TRI or DCVC, but increased necrosis induced by DCVC. In contrast, pretreatment of hPT cells with TRI or DCVC protected from Hg{sup 2+} by decreasing necrosis and increasing apoptosis. Thus, whereas pretreatment of hPT cells with Hg{sup 2+} exacerbated cellular injury due to TRI or DCVC by shifting the response from apoptosis to necrosis, pretreatment of hPT cells with either TRI or DCVC protected from Hg{sup 2+}-induced cytotoxicity by shifting the response from necrosis to apoptosis. These results demonstrate that by altering processes related to GSH status, susceptibilities of rPT and hPT cells to acute injury from Hg{sup 2+}, TRI, or DCVC are markedly altered by prior exposures.

  15. Modulatory Effect of Gonadotropins on Rats’ Ovaries after Nandrolone Decanoate Administration: A Stereological Study

    PubMed Central

    Bordbar, Hossein; Mesbah, Fakhroddin; Talaei, Tahereh; Dehghani, Farzaneh; Mirkhani, Hossein

    2014-01-01

    Background: Nandrolone decanoate (ND) is an anabolic androgenic steroid (AAS) which influences the ovarian structure and function. We assessed the effects of ND on the ovarian volume, number of primordial follicles, and level of hormones and also evaluated the modulatory effects of gonadotropins on the histopathological changes imposed by the administration of ND. Methods: Six groups of Sprague-Dawley adult female rats (n=30) were used. The experimental rats were injected intraperitoneally with 3 and 10 mg/kg ND with or without human menopausal gonadotropin (hMG), 10 IU weekly for one month. The vehicle and control rats were administered olive oil and saline, respectively, for the same period of time. The ovarian volume and number of primordial follicles were estimated by stereological methods. Results: The results showed a decrease in the ovarian volume, number of primordial follicles, and level of gonadotropins in the ND-treated animals compared with the vehicle groups. In the rats treated with 3 mg/kg of ND with hMG, an increase in the ovarian volume and number of primordial follicles was shown as compared to the rats treated with the same dose of ND without hMG. Conclusion: ND exerted detrimental effects on the dimensions of the ovary, number of follicles, and level of sex hormones. However, hMG, prevented the harmful effects of ND (at least in a low dose) on the ovarian follicles. PMID:24453393

  16. Interaction of exposure concentration and duration in determining the apoptosis of testis in rats after cigarette smoke inhalation.

    PubMed

    He, Lijuan; Gong, Haiyan; Zhang, Jing; Zhong, Chunxue; Huang, Yunfei; Zhang, Chen; Aqeel Ashraf, Muhammad

    2016-07-01

    The effects of differences in smoke concentration and exposure duration in Sprague Dawley rats to determine variation in type and severity of the testis apoptosis were evaluated. The daily dosages were 10, 20 and 30 non-filter cigarettes for a period of 2, 4, 6, 8 and 12 weeks. Mainstream smoke exposure suppressed body weight gain in all regimens. A dose-related increase in plasma nicotine concentration was observed in smoke-exposed groups for 4, 6, 8 and 12 week regimens. Histopathological examination of the exposed groups showed disturbances in the stages of spermatogenesis, tubules atrophying and these appeared to be dose-related. Cytoplasmic caspase-3 immunostaining was detected both in Sertoli cells and germ cells in smoke-exposure groups. An increase in TUNEL-positive cells of testicular cells was observed after 6 weeks of cigarette exposure. The results indicate that cigarette exposure concentration and duration have interaction effect to induce apoptosis in the rat testes. PMID:27298588

  17. Carcinogenic interactions between a single inhalation of 239PuO2 and chronic exposure to cigarette smoke in rats.

    PubMed

    Mauderly, Joe L; Seilkop, Steven K; Barr, Edward B; Gigliotti, Andrew P; Hahn, Fletcher F; Hobbs, Charles H; Finch, Gregory L

    2010-05-01

    Rats were exposed once by inhalation to plutonium-239 dioxide ((239)PuO(2)), resulting in chronic alpha-particle irradiation of the lung, and exposed chronically to cigarette smoke to examine carcinogenic interactions between the two exposures. F344 rats were exposed to (239)PuO(2) to achieve an initial lung burden of 0.5 kBq and then exposed 6 h/day, 5 days/week to cigarette smoke at 100 or 250 mg particulate matter/m(3) for up to 30 months. Exposure to cigarette smoke increased the cumulative radiation dose to lung by slowing the clearance of (239)PuO(2). (239)PuO(2) alone did not affect survival, but the higher cigarette smoke exposure shortened survival in females. Combined exposure to (239)PuO(2) and cigarette smoke acted synergistically to shorten survival in both genders. The combined effects of cigarette smoke and (239)PuO(2) were approximately additive for lung hyperplasia and adenomas but were strongly synergistic for carcinomas. Differences between observed incidences and incidences predicted by survival-adjusted models accounting for increased radiation dose revealed a substantial component of synergy for carcinomas above that attributable to the radiation dose effect. The synergy for malignant lung tumors is consistent with findings from uranium miners and nuclear weapons production workers. These results bolster confidence in the epidemiological findings and have implications for risk assessment. PMID:20426667

  18. Anabolic-androgenic steroid interaction with rat androgen receptor in vivo and in vitro: a comparative study.

    PubMed

    Feldkoren, Boris I; Andersson, Stefan

    2005-04-01

    Anabolic steroids are synthetic derivatives of testosterone and are characterized by their ability to cause nitrogen retention and positive protein metabolism, thereby leading to increased protein synthesis and muscle mass. There are disagreements in the literature in regards to the interaction of anabolic steroids with the androgen receptor (AR) as revealed by competitive ligand binding assays in vitro using cytosolic preparations from prostate and skeletal muscle. By use of tissue extracts, it has been shown that some anabolic steroids have binding affinities for the AR that are higher than that of the natural androgen testosterone, while others such as stanozolol and methanedienone have significantly lower affinities as compared with testosterone. In this study we show that stanozolol and methanedienone are low affinity ligands of the rat recombinant AR as revealed by a ligand binding assay in vitro, however, based on a cell-based AR-dependent transactivation assay, they are potent activators of the AR. We also show that a single injection of stanozolol and methanedienone causes a rapid cytosolic depletion of AR in rat skeletal muscle. Based on these results, we conclude that anabolic steroids with low affinity to AR in vitro, can in fact in vivo act on the AR to cause biological responses. PMID:15876413

  19. Interaction of Inflammation and Hyperoxia in a Rat Model of Neonatal White Matter Damage

    PubMed Central

    Prager, Sebastian; van de Looij, Yohan; Reinboth, Barbara S.; Zimmermanns, Julia; Schlager, Gerald W.; Brait, Daniela; Sifringer, Marco; Endesfelder, Stefanie; Sizonenko, Stéphane; Mallard, Carina; Bührer, Christoph; Felderhoff-Mueser, Ursula; Gerstner, Bettina

    2012-01-01

    Intrauterine infection and inflammation are major reasons for preterm birth. The switch from placenta-mediated to lung-mediated oxygen supply during birth is associated with a sudden rise of tissue oxygen tension that amounts to relative hyperoxia in preterm infants. Both infection/inflammation and hyperoxia have been shown to be involved in brain injury of preterm infants. Hypothesizing that they might be additive or synergistic, we investigated the influence of a systemic lipopolysaccharide (LPS) application on hyperoxia-induced white matter damage (WMD) in newborn rats. Three-day-old Wistar rat pups received 0.25 mg/kg LPS i.p. and were subjected to 80% oxygen on P6 for 24 h. The extent of WMD was assessed by immunohistochemistry, western blots, and diffusion tensor (DT) magnetic resonance imaging (MRI). In addition, the effects of LPS and hyperoxia were studied in an in vitro co-culture system of primary rat oligodendrocytes and microglia cells. Both noxious stimuli, hyperoxia, and LPS caused hypomyelination as revealed by western blot, immunohistochemistry, and altered WM microstructure on DT-MRI. Even so, cellular changes resulting in hypomyelination seem to be different. While hyperoxia induces cell death, LPS induces oligodendrocyte maturity arrest without cell death as revealed by TUNEL-staining and immunohistological maturation analysis. In the two-hit scenario cell death is reduced compared with hyperoxia treated animals, nevertheless white matter alterations persist. Concordantly with these in vivo findings we demonstrate that LPS pre-incubation reduced premyelinating-oligodendrocyte susceptibility towards hyperoxia in vitro. This protective effect might be caused by upregulation of interleukin-10 and superoxide dismutase expression after LPS stimulation. Reduced expression of transcription factors controlling oligodendrocyte development and maturation further indicates oligodendrocyte maturity arrest. The knowledge about mechanisms that triggered

  20. Effects of naltrexone on firing activity of rat cortex neurons and its interactions with ethanol.

    PubMed

    Kozhechkin, S N; Mednikova, Yu S; Kolik, L G

    2013-09-01

    Naltrexone dose-dependently decreased neuron firing rate in the rat frontal cortex after intravenous (1-20 mg/kg) and microelectrophoretic administration. Microelectrophoretic applications of naltrexone reduced the excitatory neuronal response of neurons to low doses of ethanol (electroosmotic application) and potentiated depression of firing activity induced by ethanol in high doses. We concluded that opioid peptides take part in generation of spontaneous neuronal activity in the frontal cortex and neuronal excitation caused by ethanol in low doses. Naltrexone acts as a synergist of ethanol in its depressive effect on cortical neurons. PMID:24288728

  1. Interaction of acupuncture and electroacupuncture on the pharmacokinetics of aspirin and the effect of brain blood flow in rats.

    PubMed

    Wu, Ming-Tsang; Shaw, Lee-Hsin; Wu, Yu-Tse; Tsai, Tung-Hu

    2013-01-01

    Acupuncture and electroacupuncture have been used to improve the brain and motor functions of poststroke patients, and aspirin is used for the prevention of stroke recurrence. Our hypothesis is that acupuncture and electroacupuncture treatments may interact with aspirin in terms of pharmacokinetics via affecting the brain blood flow. The aim of this study is to investigate the potential interactions of acupuncture and electroacupuncture on the pharmacokinetics of aspirin. The effects of acupuncture treatments on brain blood flow were measured by the laser Doppler blood flow imager. The parallel pharmacokinetic study design included three groups: control, acupuncture, and electroacupuncture groups. Two acupoints, namely, Quchi (LI 11) and Zusanli (ST 36), were needled and stimulated electronically in anaesthetized rats. The concentrations of aspirin and its metabolite, salicylic acid were determined by microdialysis and HPLC analysis after aspirin administration (30 mg/kg, i.v.). The brain blood flow responded to electroacupuncture treatments, but the pharmacokinetic parameters of aspirin and salicylic acid in blood and brain were not significantly changed by acupuncture and electroacupuncture treatments. This study may, in part, offer some evidence to support the contention that there is no significant interaction for the combination of aspirin with acupuncture or electroacupuncture. PMID:24371465

  2. Learning and memory after neonatal exposure to 3,4-methylenedioxymethamphetamine (ecstasy) in rats: interaction with exposure in adulthood.

    PubMed

    Cohen, Martha A; Skelton, Matthew R; Schaefer, Tori L; Gudelsky, Gary A; Vorhees, Charles V; Williams, Michael T

    2005-09-01

    This study determined whether developmental and adult 3,4-methylenedioxymethamphetamine (MDMA) exposures in rats have interactive effects on body temperature, learning, other behaviors, and monoamine concentrations in the hippocampus, prefrontal cortex, and striatum. Learning was assessed in the Cincinnati water maze (CWM), Morris water maze (MWM), and novel object recognition (NOR). On acquisition trials in the MWM, significant differences from developmental MDMA exposure were found on latency, cumulative distance, path length, and angle of first bearing to the goal, but the early and adult MDMA exposure group performed no worse than the developmental-only MDMA group. In the reversal trials, however, an interaction was seen: latency to the goal, cumulative distance, and angle of first bearing were increased in animals treated both developmentally and in adulthood with MDMA compared with those treated only developmentally. Other tests (elevated zero maze, CWM, NOR, and open-field activity) did not show an interaction, nor did hippocampal concentrations of serotonin or dopamine. However, several behavioral tests showed neonatal MDMA effects, including increased errors in the CWM, reduced time spent with a new object in the NOR test, and reduced locomotor activity in the open-field. By contrast, adult MDMA decreased the number of entries into open quadrants of the elevated zero maze. Litter effects were controlled by treating litter as the experimental unit and using mixed models repeated measures analyses. Correlational analyses suggested that the MWM reversal interaction involves multiple monoamine changes. The results indicate that developmental MDMA exposure can interact with adult exposure to interfere with some aspects of learning. PMID:15945064

  3. Pharmacodynamic and pharmacokinetic interaction of Panchagavya Ghrita with phenytoin and carbamazepine in maximal electroshock induced seizures in rats

    PubMed Central

    Joshi, Rupa; Reeta, K. H.; Sharma, Surinder Kumar; Tripathi, Manjari; Gupta, Yogendra Kumar

    2015-01-01

    Introduction: Traditionally, Panchagavya Ghrita (PG) has been used for the management of epilepsy, anxiety, fever and jaundice. It consists of five components of cow products namely, cow milk, clarified butter from cow milk, cow urine, curd from cow milk, and cow dung juice. Aim: To evaluate the effect of PG in maximal electroshock (MES) induced seizures model and its pharmacodynamic and pharmacokinetic interaction with phenytoin (PHT) and carbamazepine (CBZ) in rats. Materials and Methods: Male Wistar rats were administered PG 500, 1000, 2000, and 4000 mg/kg orally for 7 days and seizures were induced by MES. For interaction studies, PG (4000 mg/kg) was administered along with a sub-therapeutic dose of PHT (20 mg/kg, p.o.) and CBZ (10 mg/kg, p.o.). Behavioral parameters were assessed. Oxidative stress markers and serum levels of PHT and CBZ were estimated. Results: Tonic hind limb extension, cognitive impairment, and oxidative stress produced by MES were reversed by PG (4000 mg/kg). Co-administration of PG (4000 mg/kg) with a sub-therapeutic dose of PHT and CBZ potentiated antiepileptic effect and ameliorated cognitive impairment as well as oxidative stress. Although, there was a slight increase in serum levels of PHT and CBZ on co-administration with PG, it was statistically insignificant. Conclusion: Co-administration of PG with low doses of PHT and CBZ caused complete seizure protection. This suggests the potential of PG as an adjunct in epilepsy with improved efficacy and tolerability. PMID:27011723

  4. Interaction between Lysophosphatidic Acid, Prostaglandins and the Endocannabinoid System during the Window of Implantation in the Rat Uterus

    PubMed Central

    Sordelli, Micaela S.; Beltrame, Jimena S.; Cella, Maximiliano; Gervasi, María Gracia; Perez Martinez, Silvina; Burdet, Juliana; Zotta, Elsa; Franchi, Ana M.; Ribeiro, María Laura

    2012-01-01

    Bioactive lipid molecules as lysophosphatidic acid (LPA), prostaglandins (PG) and endocannabinoids are important mediators of embryo implantation. Based on previous published data we became interested in studying the interaction between these three groups of lipid derivatives in the rat uterus during the window of implantation. Thus, we adopted a pharmacological approach in vitro using LPA, DGPP (a selective antagonist of LPA3, an LPA receptor), endocannabinoids’ receptor selective antagonists (AM251 and AM630) and non selective (indomethacin) and selective (NS-398) inhibitors of cyclooxygenase-1 and 2 enzymes. Cyclooxygenase isoforms participate in prostaglandins’ synthesis. The incubation of the uterus from rats pregnant on day 5 of gestation (implantation window) with LPA augmented the activity and the expression of fatty acid amide hydrolase, the main enzyme involved in the degradation of endocannabinoids in the rodent uteri, suggesting that LPA decreased endocannabinoids’ levels during embryo implantation. It has been reported that high endocannabinoids are deleterious for implantation. Also, LPA increased PGE2 production and cyclooxygenase-2 expression. The incubation of LPA with indomethacin or NS-398 reversed the increment in PGE2 production, suggesting that cyclooxygenase-2 was the isoform involved in LPA effect. PGs are important mediators of decidualization and vascularization at the implantation sites. All these effects were mediated by LPA3, as the incubation with DGPP completely reversed LPA stimulatory actions. Besides, we also observed that endocannabinoids mediated the stimulatory effect of LPA on cyclooxygenase-2 derived PGE2 production, as the incubation of LPA with AM251 or AM630 completely reversed LPA effect. Also, LPA augmented via LPA3 decidualization and vascularization markers. Overall, the results presented here demonstrate the participation of LPA3 in the process of implantation through the interaction with other groups of lipid

  5. Do prenatal immune activation and maternal iron deficiency interact to affect neurodevelopment and early behavior in rat offspring?

    PubMed

    Harvey, Louise; Boksa, Patricia

    2014-01-01

    Infection and iron deficiency are common during pregnancy and studies have described altered brain development in the offspring as a result of these individual maternal exposures. Both exposures have been identified as risk factors for schizophrenia yet they have never been modeled simultaneously. We developed a rat model of prenatal immune activation on a background of maternal iron deficiency to determine whether these factors interact to affect neurodevelopment and early behavior in offspring. Pregnant rats were placed on iron sufficient (IS) or iron deficient (ID) diets from E2 to P7, and administered LPS or saline on E15/16. Iron was reduced in liver, spleen, serum and placenta from ID dams by E15. LPS administration on E15 caused greater induction of serum interleukin-6 and tumor necrosis factor-α in ID dams compared to IS dams. Offspring (P0, P7) from ID dams had reduced iron in spleen, liver and brain compared to IS, which normalized by P21. Pups from ID dams showed differences in forelimb grasp and acoustic startle, whilst pups from LPS dams displayed differences in grip ability, geotaxis reflex, cliff avoidance and acoustic startle. Offspring from LPS dams displayed reduced locomotor activity at P7 and P60; offspring from ID dams showed no change. Our findings show effects of prenatal LPS and maternal iron deficiency were additive, such that offspring exposed to both insults displayed more neurodevelopmental abnormalities than offspring exposed to one alone. Yet surprisingly there was no interaction between factors, suggesting independent mechanisms of action. PMID:24064370

  6. Immediate early gene expression reveals interactions between social and nicotine rewards on brain activity in adolescent male rats.

    PubMed

    Bastle, Ryan M; Peartree, Natalie A; Goenaga, Julianna; Hatch, Kayla N; Henricks, Angela; Scott, Samantha; Hood, Lauren E; Neisewander, Janet L

    2016-10-15

    Smoking initiation predominantly occurs during adolescence, often in the presence of peers. Therefore, understanding the neural mechanisms underlying the rewarding effects of nicotine and social stimuli is vital. Using the conditioned place preference (CPP) procedure, we measured immediate early gene (IEG) expression in animals following exposure either to a reward-conditioned environment or to the unconditioned stimuli (US). Adolescent, male rats were assigned to the following CPP US conditions: (1) Saline+Isolated, (2) Nicotine+Isolated, (3) Saline+Social, or (4) Nicotine+Social. For Experiment 1, brain tissue was collected 90min following the CPP expression test and processed for Fos immunohistochemistry. We found that rats conditioned with nicotine with or without a social partner exhibited CPP; however, we found no group differences in Fos expression in any brain region analyzed, with the exception of the nucleus accumbens core that exhibited a social-induced attenuation in Fos expression. For Experiment 2, brain tissue was collected 90min following US exposure during the last conditioning session. We found social reward-induced increases in IEG expression in striatal and amydalar subregions. In contrast, nicotine reduced IEG expression in prefrontal and striatal subregions. Reward interactions were also found in the dorsolateral striatum, basolateral amygdala, and ventral tegmental area where nicotine alone attenuated IEG expression and social reward reversed this effect. These results suggest that in general social rewards enhance, whereas nicotine attenuates, activation of mesocorticolimbic regions; however, the rewards given together interact to enhance activation in some regions. The findings contribute to knowledge of how a social environment influences nicotine effects. PMID:27435419

  7. Interaction of pinaverium (a quaternary ammonium compound) with 1,4-dihydropyridine binding sites in rat ileum smooth muscle.

    PubMed Central

    Feron, O.; Wibo, M.; Christen, M. O.; Godfraind, T.

    1992-01-01

    1. The interaction of pinaverium bromide, a quaternary ammonium compound, with binding sites for (L-type) calcium channel blockers was investigated in rat ileum smooth muscle. 2. Pinaverium inhibited [3H]-(+)-PN200-110 ([3H]-(+)-isradipine) specific binding to tissue homogenates incompletely (Ki 0.38 microM; maximal inhibition 80%). In contrast, binding to single cell preparations (obtained by collagenase treatment) and to saponin-treated homogenates was completely inhibited. These data are compatible with the view that, in untreated homogenates, 20% of [3H]-(+)-isradipine binding sites are not accessible to pinaverium because it is associated with sealed inside-out vesicles. 3. Pinaverium bromide increased the apparent KD of [3H]-(+)-isradipine binding to saponin-treated homogenates but did not significantly affect the Bmax value. Moreover, the dissociation rate constant of [3H]-(+)-isradipine binding was not changed by pinaverium. These data suggest that pinaverium interacts with the dihydropyridine binding site in a competitive manner. However, in contrast to uncharged dihydropyridine calcium antagonists, pinaverium inhibited, rather than stimulated, [3H]-diltiazem binding to rat brain membranes (at 30-37 degrees C). 4. Although Bmax values of [3H]-(+)-isradipine were similar in homogenates prepared from tissue and cells (collagenase-treated), the KD value was significantly higher in cell homogenates (166 vs 95 pM). Similarly, the Ki value of pinaverium was higher in cell preparations than in tissue homogenates (0.77 vs 0.38 microM). Thus, collagenase can significantly modify the dihydropyridine recognition site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1313732

  8. Interaction between resistin and adiponectin in the proliferation of rat vascular smooth muscle cells.

    PubMed

    Hirai, Hiroyuki; Satoh, Hiroaki; Kudoh, Akihiro; Watanabe, Tsuyoshi

    2013-02-01

    We investigated the effect between resistin and adiponectin on the proliferation of vascular smooth muscle cells (VSMCs). We confirmed that resistin significantly increases the number of rat VSMCs as well as thymidine incorporation with them, whereas adiponectin diminishes resistin-induced cell proliferation. Resistin significantly increased p42/44 mitogen-activated protein kinase (MAPK) phosphorylation within rat VSMCs, whereas adiponectin inhibited resistin-induced MAPK phosphorylation. Moreover, resistin significantly increased c-fos expression, whereas adiponectin suppressed resistin-induced c-fos expression. Cell cycle progression is a tightly controlled event that is negatively regulated by cyclin-dependent kinases inhibitors (CDKIs) such as p53, p21, and p27. Resistin significantly decreased the expression of these CDKIs, whereas adiponectin restored the resistin-induced decrease in CDKIs expression. These effects were abolished in the MAPK inhibitors. In conclusion, resistin plays a role in the development of atherosclerosis, whereas adiponectin may be an important in its prevention in insulin-resistant patients. PMID:23267839

  9. Interaction of Lactobacillus fermentum BGHI14 with Rat Colonic Mucosa: Implications for Colitis Induction

    PubMed Central

    Lukic, Jovanka; Strahinic, Ivana; Milenkovic, Marina; Golic, Natasa; Kojic, Milan; Topisirovic, Ljubisa

    2013-01-01

    The present study was carried out to test the colonic mucosal response of rats to oral supplementation with Lactobacillus fermentum BGHI14 and to correlate the tissue reaction to trinitrobenzenesulfonate (TNBS)-induced colitis with mucosal barrier alterations caused by bacterial ingestion. An immune cell-mediated reaction of healthy colonic tissue was noticed after bacterial feeding. After prolonged bacterial treatment, the observed reaction had retreated to normality, but the mRNA levels of proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) remained elevated. These data point to the chronic low-grade inflammation that could be caused by long-term probiotic consumption. Although no detrimental effects of bacterial pretreatment were noticed in colitic rats, at least in the acute state of disease, the results obtained in our study point to the necessity of reassessment of existing data on the safety of probiotic preparations. Additionally, probiotic effects in experimental colitis models might depend on time coordination of disease induction with treatment duration. PMID:23851097

  10. Effects of metoclopramide and isoprenaline in the rat vas deferens; interactions with alpha-adrenoceptors.

    PubMed Central

    Spedding, M.

    1980-01-01

    1 Metoclopramide (2.8 to 280 microM) augmented contractions of rat vas deferens preparations induced by field stimulation (6 Hz for 1 s). This effect was antagonized by phentolamine (0.1 microM). Metoclopramide (2.8 to 280 microM) did not affect phenylephrine-induced contractions. 2 Metoclopramide (2.8 to 280 microM) antagonized the inhibitory effects of clonidine on the contractions induced by field stimulation, but not the inhibitory effects of purine nucleosides. 3 From these results it is concluded that metoclopramide (2.8 to 280 microM) is a presynaptic alpha-adrenoceptor antagonist in the rat vas deferens. 4 Following beta-adrenoceptor blockade with (+/-)-propranolol (3.3 microM), (-)-isoprenaline (0.47 to 14 microM) inhibited responses to field stimulation but not to phenylephrine. These propranolol-resistant effects of isoprenaline were antagonized by metoclopramide (2.8 to 280 microM) and by phentolamine (0.1 to 10 microM), indicating that isoprenaline may stimulate presynaptic alpha-adrenoceptors in this preparation. PMID:6258684

  11. [INTERACTION OF BETA-BLOCKER PROPRANOLOL WITH RENIN-ANGIOTENSIN SYSTEM INHIBITORS IN RAT KIDNEY].

    PubMed

    Kuzmin, O B; Buchneva, N V; Landar, L N

    2016-01-01

    Propranolol injection (0.5 mg/kg, s.c.) in anesthetized rats increases diuresis 1.60 times (p < 0.05) with simultaneous 1.54- and 1.62-fold increase (p < 0.05) in sodium and potassium excretion, respectively. Preliminary inhibition of renin-angiotensin system (RAS) activity using ACE inhibitor enalapril (1 mg/kg, orally, 7 days) increases the sensitivity of rat kidney to drug, increasing its diuretic effect 2.33 times, natriuresis 2.49 times, and urine potassium excretion 1.80 times (p < 0.05). After the preliminary insertion of AT1 angiotensin receptor antagonist losartan (1 mg/kg, orally, 7 days), propranolol causes 1.8-fold increase in diuresis, 2.48-fold decrease in urine sodium, and 1.71-fold decrease in kaliuresis (p < 0.05). Preliminary administration of direct renin inhibitor aliskiren (4 mg/kg, orally, 7 days) is accompanied by 2.30-fold increase in the diuretic effect of propranolol, 2.56-fold increase in natriuresis, and 2.27-fold increase in urine potassium excretion (p < 0.05). It is concluded that the renal tissue RAS is involved in the mechanism of propranolol action in the kidney, acting as modulator preventing excessive loss of water and electrolytes with urine. PMID:27455575

  12. PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTIONS BETWEEN DEHYDROEPIANDRO-STERONE AND PREDNISOLONE IN THE RAT

    PubMed Central

    Meno-Tetang, Guy M. L.; Yi Hon, Yuen; Van Wart, Scott; Jusko, William J.

    2014-01-01

    SUMMARY The effects of multiple-dosing with dehydroepiandrosterone sulfate (DHEA-SO4) on the pharmacokinetics and pharmacodynamics of prednisolone were examined. Prednisolone (25 mg/kg i.v.) was administered to male and female Sprague-Dawley rats (250–350 g) alone and following DHEA-SO4 (4 mg/kg i.v., every 8 h for 4 days). Male control rats cleared prednisolone faster [3.68 ± 1.30 (males) vs 1.01 ± 0.7 1/h/kg; p<0.05] and had larger Vss (1.38 ± 0.459 vs 0.394 ± 0.500 1/kg; p<0.05) than females both due largely to lesser plasma protein binding. Prednisolone clearance and Vss were not altered by DHEA-SO4 in males or females. The net effect of prednisolone on basophils and plasma corticosterone did not differ with gender. DHEA-SO4 had no effect on plasma corticosterone and did not alter prednisolone action. DHEA-SO4 inhibited basophil trafficking in males, but to a lesser extent than prednisolone, and antagonized the effect of prednisolone on basophil trafficking in both sexes. The steroid-sparing effect observed with DHEA clinically may not be due to an alteration of corticosteroid pharmacokinetics but partly to its ability to affect immune functions. PMID:10707113

  13. The rat prefrontostriatal system analyzed in 3D: evidence for multiple interacting functional units.

    PubMed

    Mailly, Philippe; Aliane, Verena; Groenewegen, Henk J; Haber, Suzanne N; Deniau, Jean-Michel

    2013-03-27

    Previous studies in monkeys disclosed a specific arrangement of corticostriatal projections. Prefrontal and premotor areas form dense projection fields surrounded by diffuse terminal areas extending outside the densely innervated region and overlapping with projections from other areas. In this study, the mode of prefrontostriatal innervation was analyzed in rats using a 3D approach. Following injections of tracers in defined cortical areas, 3D maps from individual cases were elaborated and combined into a global 3D map allowing us to define putative overlaps between projection territories. In addition to providing a detailed 3D mapping of the topographic representation of prefrontal cortical areas in the rat striatum, the results stress important similarities between the rodent and primate prefrontostriatal projections. They share the dual pattern of focal and diffuse corticostriatal projections. Moreover, besides segregated projections consistent with parallel processing, the interweaving of projection territories establishes specific patterns of overlaps spatially organized along the dorsoventral, mediolateral, and anteroposterior striatal axis. In particular, the extensive striatal projection fields from the prelimbic and anterior cingulate areas, which partly overlap the terminal fields from medial, orbital, and lateral prefrontal cortical areas, provide putative domains of convergence for integration between reward, cognitive, and motor processes. PMID:23536085

  14. Actions of 2-methylpiperidine (MP) and its interactions with (-)-nicotine (N) in the dog and rat

    SciTech Connect

    Sloan, J.W.; Martin, W.R.; Bostwick, M.; Hook, R.

    1986-03-01

    (+/-)-MP is a highly specific drug for enhancing the binding of (+/-)-(/sup 3/H)N in the rat brain P/sub 2/ preparation. Competition studies employing (+/-)-(/sup 3/H)N as the labelled ligand show that this activity resides in the (+) isomer. Saturation studies employing (+/-)-(/sup 3/H)MP indicate that it binds to a very high affinity site which is presumed to be an up-regulatory site. Studies were conducted where (+/-)-MP was injected through an implanted cannula into the 4th ventricle of intact beagle-type dogs. (+/-)-MP, like low doses of (+)-N, another drug which has specificity in enhancing the binding of (+/-)-, and (-)- and (+)-(/sup 3/H)N, produced EEG synchronization and miosis. (-)-N produced analgesia where as (+/-)-MP produced hyperalgesia. In the urethane-pentobarbital anethetized rats, the i.v. infusion of (+)-MP (600 ..mu..g/kg/min for 10 min), had no effect on heart rate, blood pressure or respiration. Pretreatment with (+)-MP delayed and decreased the bradycardia, vasodepression, and enhanced tidal volume produced by (-)-N infusion (60 ..mu..g/kg/min). These data show that the pharmacologic actions of MP are different from (-)-N and hexamethonium and that MP, which enhances the binding of (+/-)- and (-)-(/sup 3/H)N at the high affinity site, appears to exert opposite effects to and antagonistic effects against (-)-N.

  15. Psychological aspects of the polycystic ovary syndrome.

    PubMed

    Farkas, Judit; Rigó, Adrien; Demetrovics, Zsolt

    2014-02-01

    An overwhelming majority of scientific literature on the polycystic ovary syndrome has utilized a medical approach to analyse the disorder and only few studies have investigated its predisposing psychological factors. This literature review sheds light on the fact that this gynaecological disorder of endocrine origin, which is becoming more frequent, can be associated with a great number of psychological symptoms (e.g. depression, anxiety, body image dissatisfaction, eating and sexual disorders, and low life satisfaction). Thus, the syndrome is significant from a therapeutic point of view as well. Authors review the psychological correlates of specific symptoms, their relationships with other psychological syndromes and analyse the psychosocial background of the disorder as well as the possibilities of psychotherapy. PMID:24188448

  16. Hirsutism and acne in polycystic ovary syndrome.

    PubMed

    Archer, Johanna S; Chang, R Jeffrey

    2004-10-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine abnormality affecting reproductive age women. Population-based studies estimate a prevalence of 5-10% [Obstet Gynecol 101 (2003) 995; Aust N Z J Obstet Gynaecol 41 (2001) 202]. The clinical characteristics of PCOS include hyperandrogenism, chronic anovulation, insulin resistance and infertility. Hyperandrogenism is generally manifested as hirsutism and acne. Both these clinical symptoms are treated with similar drug therapies, including oral contraceptive pills (OCPs), topical medications or antiandrogens such as spironolactone, flutamide and finasteride, as well as topical medications. Recent studies have shown that lower doses of these medications are as efficacious as high doses and have the advantage of decreased cost and an improved side-effect profile. Although hirsutism and acne can be considered cosmetic in nature, they cause significant social embarrassment and emotional distress. Physicians should be sensitive to these issues and approach patients in a caring and sympathetic manner. PMID:15380144

  17. Polycystic Ovary Syndrome, Obesity, and Pregnancy.

    PubMed

    Joham, Anju E; Palomba, Stefano; Hart, Roger

    2016-03-01

    Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting up to one in five reproductive-aged women. It is underpinned by insulin resistance and hyperandrogenism and is associated with metabolic, reproductive, and psychological features. Women with PCOS have higher rates of obesity and central adiposity compared with women without PCOS, and weight strongly influences prevalence and clinical severity of PCOS. Women with PCOS may have subfertility and women should be aware of factors affecting fertility, in particular the impact of obesity and age. Once pregnant, women with PCOS have significantly increased risk of pregnancy-related complications including gestational diabetes, hypertensive disorders, premature delivery, and delivery by cesarean section. The offspring of women with PCOS may have increased risk of congenital abnormalities and hospitalization in childhood. Clinicians should be aware of the increased risk and screen, prevent, and manage accordingly. PMID:26854709

  18. Estrogen-Dependent Gene Expression in the Mouse Ovary

    PubMed Central

    Liew, Seng H.; Sarraj, Mai A.; Drummond, Ann E.; Findlay, Jock K.

    2011-01-01

    Estrogen (E) plays a pivotal role in regulating the female reproductive system, particularly the ovary. However, the number and type of ovarian genes influenced by estrogen remain to be fully elucidated. In this study, we have utilized wild-type (WT) and aromatase knockout (ArKO; estrogen free) mouse ovaries as an in vivo model to profile estrogen dependent genes. RNA from each individual ovary (n = 3) was analyzed by a microarray-based screen using Illumina Sentrix Mouse WG-6 BeadChip (45,281 transcripts). Comparative analysis (GeneSpring) showed differential expression profiles of 450 genes influenced by E, with 291 genes up-regulated and 159 down-regulated by 2-fold or greater in the ArKO ovary compared to WT. Genes previously reported to be E regulated in ArKO ovaries were confirmed, in addition to novel genes not previously reported to be expressed or regulated by E in the ovary. Of genes involved in 5 diverse functional processes (hormonal processes, reproduction, sex differentiation and determination, apoptosis and cellular processes) 78 had estrogen-responsive elements (ERE). These analyses define the transcriptome regulated by E in the mouse ovary. Further analysis and investigation will increase our knowledge pertaining to how E influences follicular development and other ovarian functions. PMID:21347412

  19. Computer-Generated Ovaries to Assist Follicle Counting Experiments

    PubMed Central

    Skodras, Angelos; Marcelli, Gianluca

    2015-01-01

    Precise estimation of the number of follicles in ovaries is of key importance in the field of reproductive biology, both from a developmental point of view, where follicle numbers are determined at specific time points, as well as from a therapeutic perspective, determining the adverse effects of environmental toxins and cancer chemotherapeutics on the reproductive system. The two main factors affecting follicle number estimates are the sampling method and the variation in follicle numbers within animals of the same strain, due to biological variability. This study aims at assessing the effect of these two factors, when estimating ovarian follicle numbers of neonatal mice. We developed computer algorithms, which generate models of neonatal mouse ovaries (simulated ovaries), with characteristics derived from experimental measurements already available in the published literature. The simulated ovaries are used to reproduce in-silico counting experiments based on unbiased stereological techniques; the proposed approach provides the necessary number of ovaries and sampling frequency to be used in the experiments given a specific biological variability and a desirable degree of accuracy. The simulated ovary is a novel, versatile tool which can be used in the planning phase of experiments to estimate the expected number of animals and workload, ensuring appropriate statistical power of the resulting measurements. Moreover, the idea of the simulated ovary can be applied to other organs made up of large numbers of individual functional units. PMID:25812007

  20. Transcriptome Analysis of the Capra hircus Ovary

    PubMed Central

    Zhao, Zhong Quan; Wang, Li Juan; Sun, Xiao Wei; Zhang, Jiao Jiao; Zhao, Yong Ju; Na, Ri Su; Zhang, Jia Hua

    2015-01-01

    Background Capra hircus is an important economic livestock animal, and therefore, it is necessary to discover transcriptome information about their reproductive performance. In this study, we performed de novo transcriptome sequencing to produce the first transcriptome dataset for the goat ovary using high-throughput sequencing technologies. The result will contribute to research on goat reproductive performance. Method and Results RNA-seq analysis generated more than 38.8 million clean paired end (PE) reads, which were assembled into 80,069 unigenes (mean size = 619 bp). Based on sequence similarity searches, 64,824 (60.6%) genes were identified, among which 29,444 and 11,271 unigenes were assigned to Gene Ontology (GO) categories and Clusters of Orthologous Groups (COG), respectively. Searches in the Kyoto Encyclopedia of Genes and Genomes pathway database (KEGG) showed that 27,766 (63.4%) unigenes were mapped to 258 KEGG pathways. Furthermore, we investigated the transcriptome differences of goat ovaries at two different ages using a tag-based digital gene expression system. We obtained a sequencing depth of over 5.6 million and 5.8 million tags for the two ages and identified a large number of genes associated with reproductive hormones, ovulatory cycle and follicle. Moreover, many antisense transcripts and novel transcripts were found; clusters with similar differential expression patterns, enriched GO terms and metabolic pathways were revealed for the first time with regard to the differentially expressed genes. Conclusions The transcriptome provides invaluable new data for a functional genomic resource and future biological research in Capra hircus, and it is essential for the in-depth study of candidate genes in breeding programs. PMID:25822507

  1. Does ovary need D-chiro-inositol?

    PubMed Central

    2012-01-01

    Backgroud Polycystic Ovary Syndrome (PCOS) is a multifactorial pathology that affects 10% of the women in reproductive age being the main cause of infertility due to menstrual dysfunction. Since 1980, it is known that PCOS is associated with insulin resistance (IR). The recognition of this association has prompted extensive investigation on the relationship between insulin and gonadal function, and has turned insulin sensitizer agent as the main therapeutic choice. In particular two different polyalcohol myo-inositol and D-chiro-inositol have been shown to improve insulin resistance, hyperandrogenism and to induce ovulation in PCOS women. In particular, while data on myo-inositol and restored ovulation were consistent, data on D-chiro-inositol were not . Recently, a comparative study, proposed a D-chiro-inositol paradox in the ovary of PCOS patients hypothesizing that only myo-inositol has a specific ovarian action. In the present study we aim to further study the role played by D-chiro-inositol at ovarian level. Methods A total of 54 women, aged <40 years and diagnosed with PCOS were enrolled in this study. Patients with insulin resistance and/or hyperglycaemia were excluded from the study. Patients were randomly divided into 5 groups (n=10-12): a placebo group, and 4 groups (A-D) that received 300-600-1200-2400 mg of DCI daily respectively. All treatments were carried out for 8 weeks before follicle stimulating hormone (rFSH) administration. Results Total r-FSH units increased significantly in the two groups that received the higher doses of DCI. The number of immature oocytes was significantly increased in the three groups that received the higher doses of DCI. Concurrently, the number of MII oocytes was significantly lower in the D group compared to placebo group. Noteworthy, the number of grade I embryos was significantly reduced by DCI supplementation. Conclusions Indeed, increasing DCI dosage progressively worsens oocyte quality and ovarian response. PMID

  2. [The polycystic ovary syndrome and insulin resistance].

    PubMed

    Kreze, A; Hrnciar, J; Dobáková, M; Pekarová, E

    1997-10-01

    The insulin resistance syndrome and the polycystic ovary syndrome (PCOS) appear to have some following coincidences: the existence of subclinical acanthosis nigricans in PCOS hyperinsulinemic women, correlation of insulin levels and free testosterone, insulin-like growth factor I binding protein (IGFIBP), and sex-hormone binding globulin. Insulin and IGFI act synergically with luteinizing hormone increasing the activity of cytochrome P450c17 and its enzymatic activity in the adrenals. The decrease in IGFI level and IGFI receptors in the ovarian granulosa cells reduce the steroids aromatisation. The increased expression of IGFI receptors in the theca cells favours the androgens' synthesis. Long-term insulin therapy results in an increase in ovary volume and the blood androgens levels. The deterioration of insulin resistance in PSOC women progresses also by the reduction of type I of skeletal muscle fibres which are sensitive to insulin, and the increase of type II fibres which are resistant to insulin in hyperandrogenemia. Testosterone deteriorates the skeletal as well as hepatic insulin sensitivity by both its facilitating effect on lipolysis and the increase of free fatty acids. Abdominal obesity seen in PCOS and insulin resistance is composed by adipocytes with glucocorticoid receptors, which after cortisol stimulation activate the lipoprotein lipase and fat accumulation. Gynoid obesity with the preferential aromatisation of steroids is not evolved because of the low estrogens and progesterone levels in PCOS. Low progesterone levels (with anticortisol effect) support the development of abdominal obesity. Ultimately, the early peak of insulin secretion (4-8 min) in PCOS is higher. This fact should testify a certain diabetic disposition. (Ref. 37.) PMID:9490171

  3. Postsynaptic density protein 95-regulated NR2B tyrosine phosphorylation and interactions of Fyn with NR2B in levodopa-induced dyskinesia rat models

    PubMed Central

    Ba, Maowen; Kong, Min; Ma, Guozhao

    2015-01-01

    Context Abnormality in interactions between N-methyl-d-aspartate (NMDA) receptor and its signaling molecules occurs in the lesioned striatum in Parkinson’s disease (PD) and levodopa-induced dyskinesia (LID). It was reported that Fyn-mediated NR2B tyrosine phosphorylation, can enhance NMDA receptor function. Postsynaptic density protein 95 (PSD-95), one of the synapse-associated proteins, regulates interactions between receptor and downstream-signaling molecules. In light of the relationship between PSD-95, NR2B, and Fyn kinases, does PSD-95 contribute to the overactivity of NMDA receptor function induced by dopaminergic treatment? To further prove the possibility, the effects of regulating the PSD-95 expression on the augmented NR2B tyrosine phosphorylation and on the interactions of Fyn and NR2B in LID rat models were evaluated. Methods In the present study, parkinsonian rat models were established by injecting 6-hydroxydopamine. Subsequently, valid PD rats were treated with levodopa (50 mg/kg/day with benserazide 12.5 mg/kg/day, twice daily) intraperitoneally for 22 days to create LID rat models. Then, the effect of pretreatment with an intrastriatal injection of the PSD-95mRNA antisense oligonucleotides (PSD-95 ASO) on the rotational response to levodopa challenge was assessed. The effects of pretreatment with an intrastriatal injection of PSD-95 ASO on the augmented NR2B tyrosine phosphorylation and interactions of Fyn with NR2B in the LID rat models were detected by immunoblotting and immunoprecipitation. Results Levodopa administration twice daily for 22 days to parkinsonian rats shortened the rotational duration and increased the peak turning responses. The altered rotational responses were attenuated by PSD-95 ASO pretreatment. Meanwhile, PSD-95 ASO pretreatment decreased the level of PSD-95 protein expression and reduced both the augmented NR2B tyrosine phosphorylation and interactions of Fyn with NR2B triggered during the levodopa administration in the

  4. Differences in responsiveness of mediodorsal thalamic and medial prefrontal cortical neurons to social interaction and systemically administered phencyclidine in rats.

    PubMed

    Jodo, E; Katayama, T; Okamoto, M; Suzuki, Y; Hoshino, K; Kayama, Y

    2010-11-10

    Phencyclidine (PCP) is a psychotomimetic drug that induces schizophrenia-like symptoms in healthy individuals and behavioral abnormalities with corresponding symptoms of schizophrenia in non-human animals. Our previous studies showed that systemically administered PCP produces tonic activation of neurons in the medial prefrontal cortex (mPFC) of rats and that this activation is mainly via excitatory inputs from regions outside the mPFC. Such long-lasting activation of PFC neurons is now considered to be a pivotal factor in PCP-induced behavioral abnormalities. Although our previous study identified the ventral hippocampus as a possible source of the excitatory inputs, it is not the only source innervating the mPFC. Several regions such as the thalamus also have monosynaptic projections to the mPFC. Recently, increased c-fos expression by systemic PCP administration was reported in the mediodorsal nucleus of the thalamus (MD) and the centromedial nucleus of the thalamus (CM), which have strong reciprocal innervations with the mPFC. However, few studies have reported effects of PCP on the firing activity of MD/CM neurons in unanesthetized animals. In the current study in freely moving rats, we examined effects of systemically administered PCP on the spontaneous firing activity of the MD/CM, after identifying the response properties of recorded neurons in social interaction with an unfamiliar partner. About 30% of MD/CM neurons recorded exhibited tonic excitation following systemic PCP administration, whereas only a few neurons (7%) were inhibited by PCP. The proportion of MD neurons activated by systemic PCP administration was about half of that in the mPFC. Although the proportion of neurons responsive to social interaction did not differ between the two regions (40%), neurons activated during social interaction in the mPFC (90%) were more likely to be affected by systemic PCP administration than those in the MD/CM (45%). These results suggest that neurons

  5. Role of Notch signaling in granulosa cell proliferation and polyovular follicle induction during folliculogenesis in mouse ovary.

    PubMed

    Terauchi, Karin J; Shigeta, Yuri; Iguchi, Taisen; Sato, Tomomi

    2016-07-01

    In the fetal mouse ovary, oocytes are connected by an intercellular bridge and form germ cell cysts. Folliculogenesis begins after birth. To study the role of Notch signaling in folliculogenesis, double-immunohistochemical localization of laminin and Ki-67 was performed in mouse ovaries from embryonic day 17.5 (E17.5) to postnatal day 4 (P4). Most cysts and follicles contained Ki-67-negative cells; however, a few Ki-67-positive cells were present in cysts from E17.5 through P4, indicating that a small number of pre-granulosa cells continue to proliferate during folliculogenesis. To examine the effects of an inhibitor of Notch signaling (DAPT) and a synthetic estrogen (diethylstilbestrol [DES]) on folliculogenesis, an organ-culture system was established. The numbers of cysts, primordial follicles (PrFs) and primary follicles were unchanged by DES, whereas the total number of PrFs and of PrFs with Ki-67-negative cells was reduced by DAPT. In organ-cultured neonatal ovaries, only DAPT treatment increased degenerating cells defined as oocytes. On the contrary, the number of polyovular follicles (PFs) and the PF incidence were significantly increased in ovaries organ-cultured with DES at day 20 post-grafting. In organ-cultured fetal and neonatal ovaries, DAPT reduced Notch 3 and Hey2 mRNAs, whereas DES increased Hey2 mRNA. These results suggest that Notch signaling in fetal ovaries is involved with PrF assembly by the regulation of oocyte survival rather than by cell proliferation. In PF induction, as a result of the disruption of interactions between oocytes and pre-granulosa cells, DES and Notch signaling act independently. PMID:26899251

  6. A comparison of the multiple oocyte maturation gene expression patterns between the newborn and adult mouse ovary

    PubMed Central

    Bahmanpour, Soghra; Talaei Khozani, Tahereh; Zarei fard, Nehleh; Jaberipour, Mansoureh; Hosseini, Ahmah; Esmaeilpour, Tahereh

    2013-01-01

    Background: The interaction between follicular cells and oocyte leads to a change in gene expression involved in oocyte maturation processes. Objective: The purpose of this study was to quantify the expression of more common genes involved in follicular growth and oocyte developmental competence. Materials and Methods: In this experimental study, the expression of genes was evaluated with qRT-PCR assay in female BALB/c mice pups at 3-day of pre-pubertal and 8 week old virgin adult ovaries. The tissue was prepared by H&E staining for normal morphological appearance. The data were calculated with the 2-∆Ct formula and assessed using non-parametric two-tailed Mann-Whitney test. The p<0.05 was considered as significant. Results: The data showed a significant increase in the level of Stra8 and GDF9 in adult compared with newborn mice ovaries (p=0.049). In contrast, a significant decrease in the level of Mvh, REC8, SCP1, SCP3, and ZP2 was observed in adult mice ovaries compared to those in the newborn mice ovaries (all p=0.049 except SCP1: p=0.046). There was no significant difference in the level of OCT4 and Cx37 expression between adult and newborn mice ovaries. Conclusion: The modifications in gene expression patterns coordinate the follicular developmental processes. Furthermore, the findings showed higher expression level of premeiotic gene (Stra8) and lower level of meiotic entry markers (SCP1, SCP3, and REC8) in juvenile than newborn mouse ovaries. This article extracted from Ph.D. thesis. (Nehleh Zarei fard) PMID:24639702

  7. Ultrastructural Analysis of Drosophila Ovaries by Electron Microscopy.

    PubMed

    Hurd, Thomas R; Sanchez, Carlos G; Teixeira, Felipe K; Petzold, Chris; Dancel-Manning, Kristen; Wang, Ju-Yu S; Lehmann, Ruth; Liang, Feng-Xia A

    2015-01-01

    The Drosophila melanogaster ovary is a powerful, genetically tractable system through which one can elucidate the principles underlying cellular function and organogenesis in vivo. In order to understand the intricate process of oogenesis at the subcellular level, microscopic analysis with the highest possible resolution is required. In this chapter, we describe the preparation of ovaries for ultrastructural analysis using transmission electron microscopy and focused ion beam scanning electron microscopy. We discuss and provide protocols for chemical fixation of Drosophila ovaries that facilitate optimal imaging with particular attention paid to preserving and resolving mitochondrial membrane morphology and structure. PMID:26324436

  8. Ultrastructural Analysis of Drosophila Ovaries by Electron Microscopy

    PubMed Central

    Hurd, Thomas R.; Sanchez, Carlos G.; Teixeira, Felipe K.; Petzold, Chris; Dancel-Manning, Kristen; Wang, Ju-Yu S.; Lehmann, Ruth; Liang, Feng-Xia A.

    2016-01-01

    i. Summary The Drosophila melanogaster ovary is a powerful, genetically tractable system through which one can elucidate the principles underlying cellular function and organogenesis in vivo. In order to understand the intricate process of oogenesis at the subcellular level, microscopic analysis with the highest possible resolution is required. In this chapter, we describe the preparation of ovaries for ultrastructural analysis using transmission electron microscopy and focused ion beam scanning electron microscopy. We discuss and provide protocols for chemical fixation of Drosophila ovaries that facilitate optimal imaging with particular attention paid to preserving and resolving mitochondrial membrane morphology and structure. PMID:26324436

  9. Bilateral Cystic Lymphangioma of Ovary Associated with Chylous Ascites

    PubMed Central

    Arakeri, Surekha Ulhas; Patil, Vijaya L.; Mulay, Himanshu Dilip

    2015-01-01

    Intraabdominal cystic lymphangiomas are rare and are located in retroperitoneum, mesentery, omentum and other visceral organs. Lymphangiomas of the ovary are rare and are usually unilateral. Cases with bilateral cystic lymphangiomas of the ovary are reported very rarely in literature. We report a rare case of bilateral cystic lymphangioma of ovary associated with chylous ascites in a 35-year-old lady who presented with complaints of severe dysmenorrhoea and oligomenorrhoea since 6 months with history of chyluria for the past 3 years. PMID:26435959

  10. Interaction of Egocentric and World-Centered Reference Frames in the Rat Posterior Parietal Cortex

    PubMed Central

    Clark, Benjamin J.; Forster, Tyler C.; Tatsuno, Masami; McNaughton, Bruce L.

    2014-01-01

    Navigation requires coordination of egocentric and allocentric spatial reference frames and may involve vectorial computations relative to landmarks. Creation of a representation of target heading relative to landmarks could be accomplished from neurons that encode the conjunction of egocentric landmark bearings with allocentric head direction. Landmark vector representations could then be created by combining these cells with distance encoding cells. Landmark vector cells have been identified in rodent hippocampus. Given remembered vectors at goal locations, it would be possible to use such cells to compute trajectories to hidden goals. To look for the first stage in this process, we assessed parietal cortical neural activity as a function of egocentric cue light location and allocentric head direction in rats running a random sequence to light locations around a circular platform. We identified cells that exhibit the predicted egocentric-by-allocentric conjunctive characteristics and anticipate orienting toward the goal. PMID:24741034

  11. Effects of intranasal and peripheral oxytocin or gastrin-releasing peptide administration on social interaction and corticosterone levels in rats.

    PubMed

    Kent, Pamela; Awadia, Alisha; Zhao, Leah; Ensan, Donna; Silva, Dinuka; Cayer, Christian; James, Jonathan S; Anisman, Hymie; Merali, Zul

    2016-02-01

    The intranasal route of drug administration has gained increased popularity as it is thought to allow large molecules, such as peptide hormones, more direct access to the brain, while limiting systemic exposure. Several studies have investigated the effects of intranasal oxytocin administration in humans as this peptide is associated with prosocial behavior. There are, however, few preclinical studies investigating the effects of intranasal oxytocin administration in rodents. Oxytocin modulates hypothalamic-pituitary-adrenal (HPA) axis functioning and it has been suggested that oxytocin's ability to increase sociability may occur through a reduction in stress reactivity. Another peptide that appears to influence both social behavior and HPA axis activity is gastrin-releasing peptide (GRP), but it is not known if these GRP-induced effects are related. With this in mind, in the present study, we assessed the effects of intranasal and intraperitoneal oxytocin and GRP administration on social interaction and release of corticosterone in rats. Intranasal and intraperitoneal administration of 20, but not 5 μg, of oxytocin significantly increased social interaction, whereas intranasal and peripheral administration of GRP (20 but not 5 μg) significantly decreased levels of social interaction. In addition, while intranasal oxytocin (20 μg) had no effect on blood corticosterone levels, a marked increase in blood corticosterone levels was observed following intraperitoneal oxytocin administration. With GRP, intranasal (20 μg) but not peripheral administration increased corticosterone levels. These findings provide further evidence that intranasal peptide delivery can induce behavioral alterations in rodents which is consistent with findings from human studies. In addition, the peptide-induced changes in social interaction were not linked to fluctuations in corticosterone levels. PMID:26658172

  12. Interaction of vasoactive substances released by platelet-activating factor in the rat perfused heart.

    PubMed Central

    Hu, W. M.; Man, R. Y.

    1991-01-01

    1. The coronary vascular effects of platelet-activating factor (PAF) have been intensively studied and it has been proposed that they are mediated by the release of vasoactive substances. In this study, a cascade perfusion model using two rat perfused hearts was developed to investigate the properties of PAF-released vasoactive substances and the interplay of these substances. The properties of the vasoactive substances after an injection of PAF (100 pmol) in the rat perfused heart were examined by collecting the effluent from the first heart for the perfusion of a second (recipient) heart. The presence of vasoconstrictor substances in the effluent was characterized by an increase in the perfusion pressure of the recipient heart. 2. Previous exposure of the recipient heart of PAF (100 pmol) abolished the response of the heart to subsequent administration of PAF, but did not affect the response of the recipient heart to the effluent. This suggested that the coronary vasoconstrictor response of the recipient heart was not due to the presence of PAF in the effluent but to other vasoactive substances. 3. Pretreatment of the recipient heart with the leukotriene receptor antagonist, L-649,923 (5 microM), partially reduced the vasoconstrictor effect of the effluent. Pretreatment of the first heart with indomethacin (2.8 microM) also partially reduced the vasoconstrictor effect of the effluent. The combination of indomethacin pretreatment of the first heart and L-649,923 pretreatment of the recipient heart completely abolished the vasoconstrictor effect of the effluent suggesting that both prostaglandins and leukotrienes are involved in the vasoconstrictor effect of the effluent. 4. Pretreatment of both hearts with L-649,923 or the first heart with the leukotriene synthesis inhibitor (MK-886, 10 microM) completely abolished the vasoconstrictor effect of the effluent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1810604

  13. The expression patterns of Reg IV gene in normal rat reproduction system.

    PubMed

    Du, Fang; Yao, Zhen-Wei

    2013-01-01

    Reg IV, the latest member of the regenerating gene family, has been documented in different tissues of human and rat, such as the colon, small intestine, stomach, and pancreas. Expression of Reg IV gene in distinct cell types has been correlated with its various functions in regeneration, cell growth and survival, proliferation and differentiation, cell adhesion, and resistance to apoptosis. However, there was no evidence to show whether the Reg IV protein is present in the reproductive system of normal rat. The aim of this study was to reveal the expression patterns of Reg IV in rat ovary and uterus. The expression of Reg IV was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot at mRNA and protein levels, respectively. The localization of Reg IV protein within rat ovary and uterus was investigated by immunohistochemistry (IHC). Our results showed that the expression of Reg IV in ovary was significantly higher than that in the uterus. The strong immunoreactive signals of Reg IV was observed in granulosa cells and oocytes of ovarian follicles, corpus luteum, and interstitial cells in rat ovary; only weak signals were detected in luminal and gland epithelium of rat endometrium. These findings first demonstrate the expression of Reg IV in ovary and uterus of the healthy rat at both mRNA and protein levels. It provides an evidence of Reg IV expression in rat reproductive system, which may help elucidate a potential role in cell growth and proliferation of reproductive system. PMID:23203400

  14. Interaction of histamine and calcitonin gene-related peptide in the formalin induced pain perception in rats.

    PubMed

    Mobarakeh, Jalal Izadi; Torkaman-Boutorabi, Anahita; Rahimi, Amir Abbas; Ghasri, Shahrooz; Nezhad, Reza Mohammad Ali; Hamzely, Arash; Khoshkholgh Sima, Baharak; Takahashi, Kazuhiro; Nunoki, Kazuo; Yanai, Kazuhiko

    2011-06-01

    Histamine and calcitonin gene-related peptide (CGRP) contribute to the pain perception. The aim of the present study is to clarify the interaction of histamine and CGRP in the perception of inflammatory pain. The effects of a histamine H1 receptor antagonist (pyrilamine, i.p.), an H2 receptor antagonist (ranitidine, i.p.) and a CGRP antagonist (CGRP 8-37, i.t.) on the formalininduced pain was studied in rats. Pyrilamine and ranitidine produced a dose-dependent antinociceptive response in the first and the second phases of the formalin test. A single administration of pyrilamine (1 mg/kg, i.p.), ranitidine (10 mg/kg, i.p.) or CGRP 8-37 (10 µg/µL, i.t.) had no significant effects on the pain perception in the second phase. A combination of CGRP 8-37 and pyrilamine or ranitidine at these sub-effective doses, however, showed nociceptive response in the second phase. Moreover, a histamine (i.t.)-induced hyperalgesia was completely prevented by treatment with GGRP 8-37 at this dose. Our findings have raised the possibility that the CGRP system has interaction with histamine in the perception of inflammatory pain. PMID:21673449

  15. Antinociceptive Interactions Between Meloxicam and Gabapentin in Neuropathic Pain Depend on the Ratio used in Combination in Rats.

    PubMed

    Espinosa-Juárez, Josué Vidal; Jaramillo-Morales, Osmar Antonio; Corona-Ramos, Janette Nallely; Medina-López, José Raúl; López-Muñoz, Francisco Javier

    2016-05-01

    Preclinical Research Neuropathic pain is particularly difficult to treat because of its diverse etiologies and underlying pathophysiological mechanisms. Drug combinations have been proposed to effectively treat some neuropathies. In the present study the interaction of five combinations of meloxicam and gabapentin, were studied to assess the possible synergistic antinociceptive response in neuropathic pain using the von Frey and acetone tests in rat models. Coadministration of meloxicam and gabapentin increased the antihyperalgesic or antiallodynic effects as compared with the compounds administered alone. The area under the curve (AUC) of the antihyperalgesic effects produced by the combination of the two drugs was generally similar to the theoretical sum of effects produced by each drug alone. However, the AUC of the antiallodynic effect produced by one combination (meloxicam 1.0 mg/kg + gabapentin 10 mg/kg) was greater than the theoretical sum of the effects produced by each drug alone. The type of final interaction on the drug combinations can be additive or cause potentiation of antinociceptive effects and depends on the proportion of each compound used in dosing. Drug Dev Res 77 : 134-142, 2016. © 2016 Wiley Periodicals, Inc. PMID:27041220

  16. Interactions of CaMKII with dopamine D2 receptors: roles in levodopa-induced dyskinesia in 6-hydroxydopamine lesioned Parkinson's rats

    PubMed Central

    Zhang, SuFang; Xie, ChengLong; Wang, Qiang; Liu, ZhenGuo

    2014-01-01

    Ca2+/calmodulin-dependent protein kinase II is a synapse-enriched kinase in mammalian brains. This kinase interacts with various synaptic proteins to regulate expression and function of interacting proteins and thereby modulates synaptic transmission. CaMKII and its interacting partners are also believed to play a pivotal role in the pathogenesis of various neurological and neurodegenerative disorders, such as Parkinson's disease (PD). In this study, we found that CaMKIIα binds to dopamine D2 receptors (D2R) in vitro. A distal region in the D2R third intracellular loop harbors CaMKIIα binding. Endogenous CaMKIIα was also found to interact with native D2Rs in rat striatal neurons in which D2Rs are expressed at a high level. In addition, in a rat 6-hydroxydopamine lesioned model of PD, chronic levodopa administration induced characteristic dyskinesia. In parallel, levodopa induced an increase in CaMKIIα-D2R interactions in striatal neurons. Intrastriatal injection of a Tat-fusion and CaMKIIα-D2R interaction-dead peptide (Tat-D2Ri) reversed this increase in the interaction between two proteins. Tat-D2Ri also alleviated dyskinetic behaviors induced by levodopa. These results reveal a new interaction between CaMKIIα and D2Rs in striatal neurons which is sensitive to long-term administration of levodopa in PD rats. Prevention of the response of CaMKIIα-D2R interactions to levodopa can alleviate levodopa-induced dyskinesia. PMID:25351365

  17. Interaction of co-expressed mu- and delta-opioid receptors in transfected rat pituitary GH(3) cells.

    PubMed

    Martin, N A; Prather, P L

    2001-04-01

    mu- and delta-Opioid agonists interact in a synergistic manner to produce analgesia in several animal models. Additionally, receptor binding studies using membranes derived from brain tissue indicate that interactions between mu- and delta-opioid receptors might be responsible for the observation of multiple opioid receptor subtypes. To examine potential interactions between mu- and delta-opioid receptors, we examined receptor binding and functional characteristics of mu-, delta-, or both mu- and delta-opioid receptors stably transfected in rat pituitary GH(3) cells (GH(3)MOR, GH(3)DOR, and GH(3)MORDOR, respectively). Saturation and competition binding experiments revealed that coexpression of mu- and delta-opioid receptors resulted in the appearance of multiple affinity states for mu- but not delta-opioid receptors. Additionally, coadministration of selective mu- and delta-opioid agonists in GH(3)MORDOR cells resulted in a synergistic competition with [(3)H][D-Pen(2,5)]enkephalin (DPDPE) for delta-opioid receptors. Finally, when equally effective concentrations of [D-Ala(2),N-MePhe(4),Gly-ol(5)]enkephalin (DAMGO) and two different delta-opioid agonists (DPDPE or 2-methyl-4a alpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12a alpha-octahydroquinolino-[2,3,3-g]-isoquinoline; TAN67) were coadministered in GH(3)MORDOR cells, a synergistic inhibition of adenylyl cyclase activity was observed. These results strongly suggest that cotransfection of mu- and delta-opioid receptors alters the binding and functional characteristics of the receptors. Therefore, we propose that the simultaneous exposure of GH(3)MORDOR cells to selective mu- and delta-opioid agonists produces an interaction between receptors resulting in enhanced receptor binding. This effect is translated into an augmented ability of these agonists to inhibit adenylyl cyclase activity. Similar interactions occurring in neurons that express both mu- and delta-opioid receptors could explain observations of multiple

  18. Roles of Oxidative Stress in Polycystic Ovary Syndrome and Cancers.

    PubMed

    Zuo, Tao; Zhu, Minghui; Xu, Wenming

    2016-01-01

    Oxidative stress (OS) has received extensive attention in the last two decades, because of the discovery that abnormal oxidation status was related to patients with chronic diseases, such as diabetes, cardiovascular, polycystic ovary syndrome (PCOS), cancer, and neurological diseases. OS is considered as a potential inducing factor in the pathogenesis of PCOS, which is one of the most common complex endocrine disorders and a leading cause of female infertility, affecting 4%-12% of women in the world, as OS has close interactions with PCOS characteristics, just as insulin resistance (IR), hyperandrogenemia, and chronic inflammation. It has also been shown that DNA mutations and alterations induced by OS are involved in cancer pathogenesis, tumor cell survival, proliferation, invasion, angiogenesis, and so on. Furthermore, recent studies show that the females with PCOS are reported to have an increasing risk of cancers. As a result, the more serious OS in PCOS is regarded as an important potential incentive for the increasing risk of cancers, and this study aims to analyze the possibility and potential pathogenic mechanism of the above process, providing insightful thoughts and evidences for preventing cancer potentially caused by PCOS in clinic. PMID:26770659

  19. Roles of Oxidative Stress in Polycystic Ovary Syndrome and Cancers

    PubMed Central

    Zuo, Tao; Zhu, Minghui; Xu, Wenming

    2016-01-01

    Oxidative stress (OS) has received extensive attention in the last two decades, because of the discovery that abnormal oxidation status was related to patients with chronic diseases, such as diabetes, cardiovascular, polycystic ovary syndrome (PCOS), cancer, and neurological diseases. OS is considered as a potential inducing factor in the pathogenesis of PCOS, which is one of the most common complex endocrine disorders and a leading cause of female infertility, affecting 4%–12% of women in the world, as OS has close interactions with PCOS characteristics, just as insulin resistance (IR), hyperandrogenemia, and chronic inflammation. It has also been shown that DNA mutations and alterations induced by OS are involved in cancer pathogenesis, tumor cell survival, proliferation, invasion, angiogenesis, and so on. Furthermore, recent studies show that the females with PCOS are reported to have an increasing risk of cancers. As a result, the more serious OS in PCOS is regarded as an important potential incentive for the increasing risk of cancers, and this study aims to analyze the possibility and potential pathogenic mechanism of the above process, providing insightful thoughts and evidences for preventing cancer potentially caused by PCOS in clinic. PMID:26770659

  20. Is Ovary Removal Tied to Colon Cancer Risk?

    MedlinePlus

    ... latter group included women who'd had a hysterectomy, but no clear indication that the ovaries had ... Health News Related MedlinePlus Health Topics Colorectal Cancer Hysterectomy Ovarian Disorders About MedlinePlus Site Map FAQs Contact ...

  1. Interaction of the main components from the traditional Chinese drug pair Chaihu-Shaoyao based on rat intestinal absorption.

    PubMed

    Chen, Yan; Wang, Jinyan; Yuan, Ling; Zhou, Lei; Jia, Xiaobin; Tan, Xiaobin

    2011-01-01

    The Chaihu-Shaoyao drug pair (Bupleuri Radix and Paeoniae Radix Alba) which is a traditional Chinese drug pair, has been widely used for anti-inflammatory purposes. Saikosaponin a (SSA), saikosaponin d (SSD) and paeoniflorin are identified as the main components in the pair. The present study focused on the interaction of the main components based on investigating their intestinal absorption using a four-site perfused rat intestinal model in order to clarify the mechanism of the compatibility of Chaihu-Shaoyao. The concentrations of SSA, SSD and paeoniflorin in the intestinal perfusate were determined by LC/MS or UPLC (Ultra Performance Liquid Chromatography) methods, followed by P*(eff) (effective permeability) and 10% ABS (the percent absorption of 10 cm of intestine) calculations. The results showed that all of the three main components displayed very low permeabilities (P*(eff) < 0.4), which implied their poor absorption in the rat intestine. The absorption levels of SSA and SSD were similar in intestine and higher in ileum than those in other intestinal regions in the decreasing order: colon, jejunum and duodenum. However, there is no significant difference in the absorption of paeoniflorin in the four segments (P < 0.05). The P*(eff) values of paeoniflorin exhibited an almost 2.11-fold or 1.90-fold increase in ileum when it was co-administrated with SSA and SSD, as well as 2.42-, 2.18-fold increase in colon, respectively, whereas the absorptions of SSA and SSD were not influenced by paeoniflorin. In conclusion, SSA and SSD could promote the absorption of paeoniflorin. To some extent this might explain the nature of the compatibility mechanisms of composite formulae in TCMs. PMID:22095024

  2. Characterization of the In Vitro Kinetic Interaction of Chlorpyrifos-Oxon with Rat Salivary Cholinesterase: A Potential Biomonitoring Matrix

    SciTech Connect

    Kousba, Ahmed A. ); Poet, Torka S. ); Timchalk, Charles

    2003-02-12

    Chlorpyrifos (CPF) is a commonly used organophosphate insecticide (OP). The primary mechanism of action for CPF involves the inhibition of acetylcholinesterase (AChE) by the active metabolite, CPF-oxon, with subsequent accumulation of acetylcholine (ACh) resulting in a wide range of neutotoxicity. CPF-oxon, can likewise inhibit other non-target cholinesterases (ChE) such as butyrylcholinesterase (BuChE), which represents a detoxification mechanism and a potential biomarker of exposure/response. Biological monitoring for OPs has focused on measuring parent chemical or metabolite in blood and urine or blood ChE inhibition. Salivary biomonitoring has recently been explored as a practical method for examination of chemical exposure; however, there are a limited number of studies exploring its use for OPs. To evaluate the use of salivary ChE as a biological monitor for OP exposure, the current study characterized salivary ChE activity in Sprague-Dawley rats through its comparison with brain and plasma ChE using BW284C51 and iso-OMPA as selective inhibitors of AChE and BuChE, respectively. The study also estimated the kinetic constants describing BuChE interaction with CPF-oxon. A modified Ellman assay in conjunction with pharmacodynamic (PD) modeling was used to characterize the in vitro titration of diluted rat salivary ChE enzyme with CPF-oxon. The results indicated that, more than 95% of rat salivary ChE activity was associated with BuChE activity, total BuChE active site concentration was 0.0012 0.00013 nmol/ml saliva, reactivation rate constant (Kr) was 0.068 0.008 h-1 and inhibitory (Ki) rate constant of 8.825 and 9.80 nM-1h-1 determined experimentally and using model optimization respectively. These study results would be helpful for further evaluating the potential utility of salivary ChE as a practical tool for biological monitor of OP exposures.

  3. Protective role of theophylline and their interaction with nitric oxide (NO) in adjuvant-induced rheumatoid arthritis in rats.

    PubMed

    Pal, Rishi; Chaudhary, Manju J; Tiwari, Prafulla C; Babu, Suresh; Pant, K K

    2015-12-01

    Theophylline (non-specific PDE inhibitor) and their interactions with nitric oxide modulators were evaluated in adjuvant-induced arthritic model of rats. Wistar rats (200-300g), 8 animals per group were used in the study. The animals were injected with 0.1mL of squalene and 0.2mL of complete Freund's adjuvant on day (0) in sub-planter region of right hind paw controls received only saline. The treatment with theophylline and nitric oxide modulators were done from day 14 to day 28. Arthritis indexes, ankle diameter, paw volume, and body weight were determined to assess RA progression from day (0) to day 28. On day 28 animals were sacrificed and their blood collected for IL-10 and TNF-α cytokine levels and hind paw for pathological analysis. Synovial fluid from joint spaces of CFA inoculated rats was collected to estimate TNF-α level in synovial fluid. The data obtained was analyzed by two-way ANOVA followed by the Newman-Keuls post-hoc test. Theophylline (10 and 20mg/kg) significantly decreased adjuvant induced increased arthritis-index, paw volume and ankle diameter (p<0.05 in all parameters) compared to only adjuvant control group. It also reversed adjuvant induced slight decrease in body weight to normalcy. l-Arginine 100mg/kg+theophylline 20mg/kg suppressed TNF-α and elevates IL-10 level as well as reversed adjuvant-induced elevated arthritic parameters as compared to only adjuvant and prednisone group (p<0.001). Synovial TNF-α level of adjuvant only group was several fold higher than its serum level. Treatment with theophylline 20mg/kg significantly reduces synovial TNF-α level as compared to adjuvant only group. Theophylline 20mg/kg+L-NAME 10mg/kg significantly reversed these adjuvant-induced changes in immunological, histopathological and arthritis parameters (p<0.05). PMID:26349791

  4. Mucin-producing tumors of the ovary: MR imaging appearance.

    PubMed

    Laurent, P-E; Thomassin-Piana, J; Jalaguier-Coudray, A

    2015-11-01

    Mucin-producing tumors of the ovary can be either primary epithelial mucin-producing tumors or ovarian metastases from a remote adenocarcinoma usually originating from the gastrointestinal tract. The purpose of this pictorial review is to describe the main types of primary or secondary mucin-producing tumors of the ovary and to provide MR imaging diagnostic criteria in order to guide further therapy. PMID:25753545

  5. Interactions of ethanol and quinidine on contractility and myocyte action potential in the rat ventricle.

    PubMed

    Guthrie, S K; Wilde, D W; Brown, R A; Savage, A O; Bleske, B

    1995-01-01

    The combined effects of ethanol and quinidine on cardiac electromechanical coupling are unknown, but both drugs affect cardiac conduction and can cause myocardial depression. Isolated left ventricular papillary and ventricular myocytes were used to assess the combined effects of quinidine and ethanol on the electrophysiologic and mechanical properties of rat myocardium. The combination of quinidine (1-300 microM) and ethanol (120-240 mg/dL) depressed active papillary muscle tension within the clinically useful concentration range. In electrophysiologic studies of isolated ventricular myocytes, quinidine prolonged the action potential duration at 50% (APD50) and 90% (APD90) repolarization, the absolute refractory period, and the relative refractory period, but decreased the maximum rate of change of depolarization in phase 0 (Vmax). When cells were exposed to ethanol (240 mg/dL) and quinidine (1.5 microM) together, a significant decrease in the quinidine-induced prolongation of the absolute refractory and relative refractory periods was seen. Additional changes in action potential parameters from the quinidine values included slight reductions in Vmax and in APD50 and APD90, but these reductions were not consistently displayed, nor were they statistically significant. PMID:7897336

  6. Interactions of ethanol on the acute toxicity of cocaine in the rat

    SciTech Connect

    Trouve, R. ); Latour, C ); Nahas, G.G. Columbia Univ., New York, NY )

    1992-02-26

    Administration of 65 mg/kg in the awake rate, restrained and instrumented, is associated with cardiovascular toxicity, convulsions and lethality within 9 feet 44 inches {plus minus} 4 feet 56 inches. Such an outcome is prevented if selected Ca{sup 2+} antagonists are administered intraarterially 5 minutes following cocaine. Four additional groups of Sprague Dawley rats were studied. The first was administered I.P. ethanol 1.5-2.0 gr. Such doses were well tolerated only producing hypertension of 50 minutes duration and all animals survived without apparent ill effects. Second and third groups were first administered the same doses of ethanol and 15 minutes later 65 mg/kg of cocaine. Survival time was 5 feet 49 inches with 1.5 mg/kg ethanol and 5 feet 57 inches {plus minus} 1 foot 26 inches with 2 mg/kg, significantly less than after cocaine administration alone. In a fourth group, animals were treated intraarterially with nicardipine or flunarizine, 2 minutes after cocaine. Survival time was not different from saline control. Ethanol enhances significantly cocaine lethal toxicity in the rate and prevents the protective effects of antidotes to this alkaloid.

  7. Interaction of insulin with the rat diaphragm. Subcellular distribution of insulin and its receptor

    SciTech Connect

    Brush, J.S.; Guzman-Diaz, A.; Celis, J.

    1987-05-01

    In studying the uptake and processing of A-14( SVI)monoiodoinsulin by isolated rat hemidiaphragms it was found that major amounts of the hormone are associated with the debris fraction. A method was developed for separating debris components by discontinuous sucrose density gradient centrifugation. Major amounts of radioactivity were associated with its myofibril component with much lower amounts in its sarcolemmal elements. Using a modified method of Marshall, et. al. insulin receptor was measurable in these fractions with greatest amounts in myofibril and microsomal fractions. Receptor was also detectable in the latter after gel electrophoresis and immunoblotting with receptor antiserum. Sarcolemmal marker enzyme (K -stimulated, ouabain-suppressible p-nitrophenylphosphate phosphatase) activity was insignificant in sarcolemmal and myofibril fractions, but was significant in the microsomal fraction. Sarcolemmal activity becomes significant after hemidiaphragm incubation with 1 M insulin for 90 sec. but does not change in the microsomal fraction. It is concluded that 1) a component bound to the myofibrils in muscle is important in insulin processing, and 2) the largest part of sarcolemmal insulin receptors are incorporated in the microsomal fraction of homogenized tissue.

  8. Differentiation of normal and cultured preneoplastic tracheal epithellal cells in rats: importance of epithelial mesenchymal interactions

    SciTech Connect

    Terzaghi, M.; Klein-Szanto, A.J.P.

    1980-11-01

    Changes in the dependence on mesenchymal tissues for survival and differentiation in inbred F344 female rats were investigated in tracheal epithelial cells exposed to 7,12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoylphorbol 13-acetate (TPA). Fresh suspensions of normal tracheal epithelium or cultured preneoplastic cells were inoculated into isolated organ segments (trachea, esophagus, bladder, or small intestine) or into Dacron containers that were then implanted subdermally into isogenic recipients. At various times after cell inoculation and implantation, tissues were removed for histologic evaluation. Normal cells inoculated into frozen-thawed trachea, esophagus, bladder, and intestine yielded a regular mucociliary epithelium. Normal cell inocula did not, however, survive in trachea previously heated (100/sup 0/C), fixed in ethanol, or digested with collagenese; nor did normal cells survive in Dacron containers unless tracheal fibroblasts plus epithelial cells were inoculated together. DMBA- and TPA-exposed cell populations with increased growth capacity in vitro survived and differentiated on all of the above substrates. For survival and differentiation in vivo, preneoplastic cells appeared to have less stringent substrate requirements than did normal cells. Application of the described techniques to the study of changes occurring early in the development of neoplastic disease is discussed.

  9. Interaction of a vasopressin antagonist with vasopressin receptors in the septum of the rat brain

    SciTech Connect

    Dorsa, D.M.; Brot, M.D.; Shewey, L.M.; Meyers, K.M.; Szot, P.; Miller, M.A.

    1988-01-01

    The ability of d(CH2)5-Tyr(Me)-arginine-8-vasopressin, an antagonist of peripheral pressoric (V1-type) vasopressin receptors, to label vasopressin binding sites in the septum of the rat brain was evaluated. Using crude membrane preparations from the septum, /sup 3/H-arginine-8-vasopressin (AVP) specifically labels a single class of binding sites with a Kd of 2.9 nM and maximum binding site concentration of 19.8 fmole/mg protein. /sup 3/H-Antag also labels a single class of membrane sites but with higher affinity (Kd = 0.47 nM) and lower capacity (10.1 fmole/mg protein) than /sup 3/H-AVP. The rank order of potency of various competitor peptides for /sup 3/H-AVP and /sup 3/H-Antag binding was similar. Oxytocin was 100-1,000 fold less potent than AVP in competing for binding with both ligands. /sup 3/H-AVP and /sup 3/H-Antag showed similar labeling patterns when incubated with septal tissue slices. Unlabeled Antag also effectively antagonized vasopressin-stimulated phosphatidylinositol hydrolysis in septal tissue slices.

  10. Interaction of Age and Mechanical Stability on Bone Defect Healing: An Early Transcriptional Analysis of Fracture Hematoma in Rat

    PubMed Central

    Ode, Andrea; Duda, Georg N.; Geissler, Sven; Pauly, Stephan; Ode, Jan-Erik; Perka, Carsten; Strube, Patrick

    2014-01-01

    Among other stressors, age and mechanical constraints significantly influence regeneration cascades in bone healing. Here, our aim was to identify genes and, through their functional annotation, related biological processes that are influenced by an interaction between the effects of mechanical fixation stability and age. Therefore, at day three post-osteotomy, chip-based whole-genome gene expression analyses of fracture hematoma tissue were performed for four groups of Sprague-Dawley rats with a 1.5-mm osteotomy gap in the femora with varying age (12 vs. 52 weeks - biologically challenging) and external fixator stiffness (mechanically challenging). From 31099 analysed genes, 1103 genes were differentially expressed between the six possible combinations of the four groups and from those 144 genes were identified as statistically significantly influenced by the interaction between age and fixation stability. Functional annotation of these differentially expressed genes revealed an association with extracellular space, cell migration or vasculature development. The chip-based whole-genome gene expression data was validated by q-RT-PCR at days three and seven post-osteotomy for MMP-9 and MMP-13, members of the mechanosensitive matrix metalloproteinase family and key players in cell migration and angiogenesis. Furthermore, we observed an interaction of age and mechanical stimuli in vitro on cell migration of mesenchymal stromal cells. These cells are a subpopulation of the fracture hematoma and are known to be key players in bone regeneration. In summary, these data correspond to and might explain our previously described biomechanical healing outcome after six weeks in response to fixation stiffness variation. In conclusion, our data highlight the importance of analysing the influence of risk factors of fracture healing (e.g. advanced age, suboptimal fixator stability) in combination rather than alone. PMID:25187955

  11. Quantitation of Cotinine and its Metabolites in Rat Plasma and Brain Tissue by Hydrophilic Interaction Chromatography Tandem Mass Spectrometry (HILIC-MS/MS)

    PubMed Central

    Li, Pei; Beck, Wayne D.; Callahan, Patrick M.; Terry, Alvin V.; Bartlett, Michael G.

    2014-01-01

    In this work, we developed a sensitive method to quantify cotinine (COT), norcotinine (NCOT), trans-3′-hydroxycotinine (OHCOT) and cotinine-N-oxide (COTNO) in rat plasma and brain tissue, using solid phase extraction (SPE), hydrophilic interaction liquid chromatography (HILIC) and tandem mass spectrometry (MS/MS). The linear range was 1–100 ng/ml for each analyte in rat plasma and brain homogenate (3–300 ng/g brain tissue). The method was validated with precision within 15% relative standard deviation (RSD) and accuracy within 15% relative error (RE). Stable isotope-labeled internal standards (IS) were used for all the analytes to achieve good reproducibility, minimizing the influence of recovery and matrix effects. This method can be used in future studies to simultaneously determine the concentrations of COT and three major metabolites in rat plasma and brain tissue. PMID:23022114

  12. Expression of preproenkephalin-like mRNA and its peptide products in mammalian testis and ovary.

    PubMed Central

    Kilpatrick, D L; Howells, R D; Noe, M; Bailey, L C; Udenfriend, S

    1985-01-01

    The distribution of preproenkephalin mRNA and proenkephalin-derived peptides have been examined in gonadal tissues from rats, hamsters, and cattle. A preproenkephalin mRNA band was detected in the ovaries of all three species and in hamster testis that is identical in size to the 1450-nucleotide mRNA typically found in tissues that express proenkephalin. Rat testis, on the other hand, expresses at least one preproenkephalin-like mRNA that is substantially greater in size (1900 nucleotides). [Met]enkephalin-containing peptides were also detected in each of the gonadal tissues examined. Although the abundance of preproenkephalin-like mRNA in rat testis was comparable to that in rat brain, the testicular content of proenkephalin-derived [Met]enkephalin sequences was less than 4% of the rat brain content. Together these data suggest that preproenkephalin-like mRNA in rat testis is not efficiently translated, proenkephalin-derived peptides undergo rapid turnover in this tissue, or the mRNA in rat testis has a frameshift resulting in an altered coding sequence. Images PMID:3864164

  13. Adrenergic and cholinergic inputs in preoptic area of rats interact for sleep-wake thermoregulation.

    PubMed

    Mallick, B N; Joseph, M M

    1998-10-01

    Isolated studies have shown that both norepinephrine and acetylcholine into the medial preoptico-anterior hypothalamic area tonically regulate sleep-wake and body temperature. A possible interaction between these neurotransmitters for the regulation of such functions has been investigated in this study. To study this interaction a combination of either prazosin and carbachol or, scopolamine and methoxamine was injected into the medial preoptico-anterior hypothalamic area and the effect on sleep, wake, and rectal temperature recorded simultaneously. The combination of chemicals were selected based on our previous studies where it was observed that each of the chemicals in a combination had opposite effects. It was observed that injection of the combination expressed a resultant summated effects of individual component chemicals when injected in isolation (observed in previous studies). Because effect of neither of the chemicals in the combination was dominant, the results suggest an interaction and integration of the adrenergic and cholinergic inputs in the medial preoptico-anterior hypothalamic area for the regulation of sleep-wakefulness and body temperature. PMID:9738535

  14. Fetal programming of polycystic ovary syndrome

    PubMed Central

    Gur, Esra Bahar; Karadeniz, Muammer; Turan, Guluzar Arzu

    2015-01-01

    Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects up to 6.8% of reproductive age women. Experimental research and clinical observations suggest that PCOS may originate in the very early stages of development, possibly even during intrauterine life. This suggests that PCOS is either genetically-transmitted or is due to epigenetic alterations that develop in the intrauterine microenvironment. Although familial cases support the role of genetic factors, no specific genetic pattern has been defined in PCOS. Several candidate genes have been implicated in its pathogenesis, but none can specifically be implicated in PCOS development. Hypotheses based on the impact of the intrauterine environment on PCOS development can be grouped into two categories. The first is the “thrifty” phenotype hypothesis, which states that intrauterine nutritional restriction in fetuses causes decreased insulin secretion and, as a compensatory mechanism, insulin resistance. Additionally, an impaired nutritional environment can affect the methylation of some specific genes, which can also trigger PCOS. The second hypothesis postulates that fetal exposure to excess androgen can induce changes in differentiating tissues, causing the PCOS phenotype to develop in adult life. This review aimed to examine the role of fetal programming in development of PCOS. PMID:26185601

  15. Cognitive functioning in polycystic ovary syndrome.

    PubMed

    Barnard, L; Balen, A H; Ferriday, D; Tiplady, B; Dye, L

    2007-01-01

    To date there have been no published studies of cognitive functioning in polycystic ovary syndrome (PCOS). This large internet-based study compared neuropsychological functioning in right-handed women with (minimum n=135) and without PCOS (minimum n=322), stratified according to use of anti-androgen medication and level of depression. Women with PCOS are thought to have hyperandrogenism and hyperestrogenism which was hypothesized to differentially influence cognitive function across cognitive domains. Performance did not differ according to diagnosis on mental rotation and spatial location tasks. Hence, no evidence to support the view that women with PCOS display a more masculine cognitive profile due to hyperandrogenism. Despite presumed hyperestrogenism, women with PCOS demonstrated impaired performance in terms of speed and accuracy, on reaction time and word recognition tasks. These findings are intriguing given the well-documented roles of estrogen and testosterone in cognitive function. Overall, these findings suggest that PCOS is not associated with masculinized cognitive functioning, and, although associated with impaired performance on tasks considered to demonstrate female-advantage, such impairments are subtle and are unlikely to affect daily functioning. PMID:17659845

  16. Polycystic Ovary Syndrome in the Pediatric Population

    PubMed Central

    2010-01-01

    Abstract Polycystic ovary syndrome (PCOS) is a common disorder characterized by hyperandrogenism and disordered gonadotropin secretion, often associated with insulin resistance. The syndrome, which modulates both hormonal and metabolic processes, is the most common endocrinopathy in reproductive-age women and increases a woman's risk of infertility, endometrial pathology, and cardiometabolic disease. As it is currently defined, PCOS most likely encompasses several distinct diseases with similar clinical phenotypes but different underlying pathophysiological processes. However, hyperandrogenism remains the syndrome's clinical hallmark. The clinical manifestations of PCOS often emerge during childhood or in the peripubertal years, suggesting that the syndrome is influenced by fetal programming and/or early postnatal events. However, given that the full clinical spectrum of PCOS does not typically appear until puberty, a “two-hit” hypothesis has been proposed: (1) a girl develops hyperandrogenism via one or more of many different potential mechanisms; (2) the preexisting hyperandrogenism subsequently disturbs the hypothalamic–pituitary–ovarian axis, resulting in ovulatory dysfunction and sustained hyperandrogenism. No consensus guidelines exist regarding the diagnosis and management of PCOS in the pediatric population; however, because the syndrome is a diagnosis of exclusion, the clinical evaluation of girls suspected of having PCOS is aimed at excluding other causes of androgen excess and menstrual dysfunction. For the syndrome's management, emphasis is placed on lifestyle and symptom-directed treatment. PMID:20939704

  17. Proteomic Analysis of Chinese Hamster Ovary Cells

    PubMed Central

    Baycin-Hizal, Deniz; Tabb, David L.; Chaerkady, Raghothama; Chen, Lily; Lewis, Nathan E.; Nagarajan, Harish; Sarkaria, Vishaldeep; Kumar, Amit; Wolozny, Daniel; Colao, Joe; Jacobson, Elena; Tian, Yuan; O'Meally, Robert N.; Krag, Sharon S.; Cole, Robert N.; Palsson, Bernhard O.; Zhang, Hui; Betenbaugh, Michael

    2013-01-01

    In order to complement the recent genomic sequencing of Chinese hamster ovary (CHO) cells, proteomic analysis was performed on CHO including the cellular proteome, secretome, and glycoproteome using tandem mass spectrometry (MS/MS) of multiple fractions obtained from gel electrophoresis, multi-dimensional liquid chromatography, and solid phase extraction of glycopeptides (SPEG). From the 120 different mass spectrometry analyses generating 682,097 MS/MS spectra, 93,548 unique peptide sequences were identified with at most a 0.02 false discovery rate (FDR). A total of 6164 grouped proteins were identified from both glycoproteome and proteome analysis, representing an 8-fold increase in the number of proteins currently identified in the CHO proteome. Furthermore, this is the first proteomic study done using CHO genome exclusively which provides for more accurate identification of proteins. From this analysis, the CHO codon frequency was determined and found to be distinct from humans, which will facilitate expression of human proteins in CHO cells. Analysis of the combined proteomic and mRNA data sets indicated the enrichment of a number of pathways including protein processing and apoptosis but depletion of proteins involved in steroid hormone and glycosphingolipid metabolism. 504 of the detected proteins included N-acetylation modifications and 1292 different proteins were observed to be N-glycosylated. This first large-scale proteomic analysis will enhance the knowledge base about CHO capabilities for recombinant expression and provide information useful in cell engineering efforts aimed at modifying CHO cellular functions. PMID:22971049

  18. Fetal programming of polycystic ovary syndrome.

    PubMed

    Gur, Esra Bahar; Karadeniz, Muammer; Turan, Guluzar Arzu

    2015-07-10

    Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects up to 6.8% of reproductive age women. Experimental research and clinical observations suggest that PCOS may originate in the very early stages of development, possibly even during intrauterine life. This suggests that PCOS is either genetically-transmitted or is due to epigenetic alterations that develop in the intrauterine microenvironment. Although familial cases support the role of genetic factors, no specific genetic pattern has been defined in PCOS. Several candidate genes have been implicated in its pathogenesis, but none can specifically be implicated in PCOS development. Hypotheses based on the impact of the intrauterine environment on PCOS development can be grouped into two categories. The first is the "thrifty" phenotype hypothesis, which states that intrauterine nutritional restriction in fetuses causes decreased insulin secretion and, as a compensatory mechanism, insulin resistance. Additionally, an impaired nutritional environment can affect the methylation of some specific genes, which can also trigger PCOS. The second hypothesis postulates that fetal exposure to excess androgen can induce changes in differentiating tissues, causing the PCOS phenotype to develop in adult life. This review aimed to examine the role of fetal programming in development of PCOS. PMID:26185601

  19. Proteomic analysis of Chinese hamster ovary cells.

    PubMed

    Baycin-Hizal, Deniz; Tabb, David L; Chaerkady, Raghothama; Chen, Lily; Lewis, Nathan E; Nagarajan, Harish; Sarkaria, Vishaldeep; Kumar, Amit; Wolozny, Daniel; Colao, Joe; Jacobson, Elena; Tian, Yuan; O'Meally, Robert N; Krag, Sharon S; Cole, Robert N; Palsson, Bernhard O; Zhang, Hui; Betenbaugh, Michael

    2012-11-01

    To complement the recent genomic sequencing of Chinese hamster ovary (CHO) cells, proteomic analysis was performed on CHO cells including the cellular proteome, secretome, and glycoproteome using tandem mass spectrometry (MS/MS) of multiple fractions obtained from gel electrophoresis, multidimensional liquid chromatography, and solid phase extraction of glycopeptides (SPEG). From the 120 different mass spectrometry analyses generating 682,097 MS/MS spectra, 93,548 unique peptide sequences were identified with at most 0.02 false discovery rate (FDR). A total of 6164 grouped proteins were identified from both glycoproteome and proteome analysis, representing an 8-fold increase in the number of proteins currently identified in the CHO proteome. Furthermore, this is the first proteomic study done using the CHO genome exclusively, which provides for more accurate identification of proteins. From this analysis, the CHO codon frequency was determined and found to be distinct from humans, which will facilitate expression of human proteins in CHO cells. Analysis of the combined proteomic and mRNA data sets indicated the enrichment of a number of pathways including protein processing and apoptosis but depletion of proteins involved in steroid hormone and glycosphingolipid metabolism. Five-hundred four of the detected proteins included N-acetylation modifications, and 1292 different proteins were observed to be N-glycosylated. This first large-scale proteomic analysis will enhance the knowledge base about CHO capabilities for recombinant expression and provide information useful in cell engineering efforts aimed at modifying CHO cellular functions. PMID:22971049

  20. Cardiometabolic Aspects of the Polycystic Ovary Syndrome

    PubMed Central

    Tan, Bee K.; Weickert, Martin O.; Lois, Konstantinos; Nestler, John E.; Sattar, Naveed; Lehnert, Hendrik

    2012-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age and is associated with various metabolic perturbations, in addition to chronic anovulation and factors related to androgen excess. In general, women live longer than men and develop cardiovascular disease at an older age. However, women with PCOS, as compared with age- and body mass index-matched women without the syndrome, appear to have a higher risk of insulin resistance, hyperinsulinemia, glucose intolerance, dyslipidemia, and an increased prothrombotic state, possibly resulting in a higher rate of type 2 diabetes mellitus, fatty liver disease, subclinical atherosclerosis, vascular dysfunction, and finally cardiovascular disease and mortality. Further alterations in PCOS include an increased prevalence of sleep apnea, as well as various changes in the secretion and/or function of adipokines, adipose tissue-derived proinflammatory factors and gut hormones, all of them with direct or indirect influences on the complex signaling network that regulates metabolism, insulin sensitivity, and energy homeostasis. Reviews on the cardiometabolic aspects of PCOS are rare, and our knowledge from recent studies is expanding rapidly. Therefore, it is the aim of the present review to discuss and to summarize the current knowledge, focusing on the alterations of cardiometabolic factors in women with PCOS. Further insight into this network of factors may facilitate finding therapeutic targets that should ameliorate not only ovarian dysfunction but also the various cardiometabolic alterations related to the syndrome. PMID:22829562

  1. Pregnancy complications in polycystic ovary syndrome patients.

    PubMed

    Katulski, Krzysztof; Czyzyk, Adam; Podfigurna-Stopa, Agnieszka; Genazzani, Andrea R; Meczekalski, Blazej

    2015-02-01

    Infertility is a widely disputed problem affecting patients suffering from polycystic ovary syndrome (PCOS). As a serious dysfunction, it frequently occurs in PCOS patients. It is, therefore, important to devote more attention to pregnancy in PCOS sufferers. According to various data, the risk of miscarriage in PCOS women is three times higher than the risk of miscarriage in healthy women. Unfortunately, the risk of most frequent pregnancy pathologies is also higher for PCOS patients, as gestational diabetes (GD), pregnancy-induced hypertension and pre-eclampsia, and small for gestational age (SGA) children. Impaired glucose tolerance and GD in pregnant PCOS patients occur more frequently than in healthy women. A quadruple increase in the risk of pregnancy-induced hypertension linked to arterial wall stiffness has also been observed in PCOS patients. The risk of pre-eclampsia, the most severe of all complications, is also four times higher in those suffering from PCOS. Pre-eclampsia is also more frequent in patients presenting additional risk factors accompanying PCOS, such as obesity or GD. At that point, it should be mentioned that PCOS patients are under 2.5 higher risk of giving birth to SGA children than healthy women. It appears that SGA can be linked to insulin resistance and insulin-dependent growth dysfunction. Therefore, PCOS pregnant women are patients of special obstetrical care. PMID:25356655

  2. Treatment options for polycystic ovary syndrome

    PubMed Central

    Badawy, Ahmed; Elnashar, Abubaker

    2011-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. The clinical manifestation of PCOS varies from a mild menstrual disorder to severe disturbance of reproductive and metabolic functions. Management of women with PCOS depends on the symptoms. These could be ovulatory dysfunction-related infertility, menstrual disorders, or androgen-related symptoms. Weight loss improves the endocrine profile and increases the likelihood of ovulation and pregnancy. Normalization of menstrual cycles and ovulation could occur with modest weight loss as little as 5% of the initial weight. The treatment of obesity includes modifications in lifestyle (diet and exercise) and medical and surgical treatment. In PCOS, anovulation relates to low follicle-stimulating hormone concentrations and the arrest of antral follicle growth in the final stages of maturation. This can be treated with medications such as clomiphene citrate, tamoxifen, aromatase inhibitors, metformin, glucocorticoids, or gonadotropins or surgically by laparoscopic ovarian drilling. In vitro fertilization will remain the last option to achieve pregnancy when others fail. Chronic anovulation over a long period of time is also associated with an increased risk of endometrial hyperplasia and carcinoma, which should be seriously investigated and treated. There are androgenic symptoms that will vary from patient to patient, such as hirsutism, acne, and/or alopecia. These are troublesome presentations to the patients and require adequate treatment. Alternative medicine has been emerging as one of the commonly practiced medicines for different health problems, including PCOS. This review underlines the contribution to the treatment of different symptoms. PMID:21339935

  3. Interaction of slow cortical rhythm with somatosensory information processing in urethane-anesthetized rats

    PubMed Central

    Toth, Attila; Gyengesi, Erika; Zaborszky, Laszlo; Detari, Laszlo

    2008-01-01

    Slow cortical rhythm (SCR) is a rhythmic alteration of active (hypopolarized), and silent (hyperpolarized) epochs in cortical cells. SCR was found to influence sensory information processing in various models, but these studies yielded inconsistent results. We examined sensory processing in anesthetized rats during SCR by recording multiple unit activity (MUA) and evoked field potentials (eFPs). Evoked field potentials as well as spontaneous FPs changes around spontaneous activations were analyzed by subsequent current source density (CSD) analysis. MUA responses and eFPs were recorded from the hindlimb area (HL) of the somatosensory cortex (SI) to electrical stimuli of the tibial nerve during active and silent states, respectively. Stimulus-associated MUA above the ongoing background activity did not differ significantly in active vs. silent states. Short latency (< 50 ms) eFP responses consisted of a sequence of deep-negative and deep-positive waves. Parameters of the first negative deflection were similar in both states. Stimulation in the silent state occasionally induced 500-700 ms long spindles in the alpha range (10-16 Hz). Spindles were never observed in responses to active state stimulation. CSD analysis showed moderately different cortical sink-source patterns when the stimulus was applied during active vs. silent state. Sinks first appeared in layer IV, V and VI, corresponding sources were in layer I/II, V and VI. Stronger activation appeared in the infraganular layers in the case of active state. CSD of spontaneous FPs revealed some sequential activation pattern in the cortex when strongest and earlier sink appeared in layer III during active states. PMID:18588861

  4. Interactions of ( sup 3 H)amphetamine with rat brain synaptosomes. II. Active transport

    SciTech Connect

    Zaczek, R.; Culp, S.; De Souza, E.B. )

    1991-05-01

    The accumulation of 5 nM d-({sup 3}H)amphetamine (d-({sup 3}H)AMPH) into rat brain synaptosomes was examined using physiological buffer conditions. The accumulation of d-({sup 3}H)AMPH into striatal synaptosomes was saturable, of high affinity, ouabain-sensitive and temperature-dependent, suggesting an active transport phenomenon. Eadee-Hofstee analysis of striatal d-({sup 3}H)AMPH transport (AMT) saturation isotherms indicated an apparent Km of 97 nM and a Vmax of 3.0 fmol/mg tissue/min. Lesion of the striatal dopaminergic innervation led to equivalent decreases of ({sup 3}H) dopamine (DA) transport and AMT, indicating that AMT occurs in DA terminals. Furthermore, AMT was not evident in cerebral cortex, a brain region with a paucity of DA terminals. In competition studies, AMT was stereospecific; d-AMPH (IC50 = 60 nM) was an 8-fold more potent inhibitor of the transport than its I-isomer (IC50 = 466 nM). DA(IC50 = 257 nM), DA uptake blockers and substrates were found to be potent inhibitors of AMT: GBR12909 IC50 = 5 nM; methamphetamine IC50 = 48 nM; methylphenidate IC50 = 53 nM; and cocaine IC50 = 172 nM. In contrast, serotonin was relatively weak in inhibiting AMT (IC50 = 7.9 microM). There was a highly significant (P less than .001; slope = 1.2) linear correlation between the AMT-inhibiting potencies of AMPH analogs and their potencies in stimulating locomotor activity in rodents. AMT may be important in the low dose effects of AMPH such as increased locomotor activity in rodents and stimulant activity in man. Differences between AMT and d-({sup 3}H)AMPH sequestration described earlier, as well as their possible relevance to behavioral and neurochemical sequelae of AMPH administration are also discussed.

  5. The modified hole board--measuring behavior, cognition and social interaction in mice and rats.

    PubMed

    Labots, Maaike; Van Lith, Hein A; Ohl, Frauke; Arndt, Saskia S

    2015-01-01

    This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure multiple dimensions of unconditioned behavior in small laboratory mammals (e.g., mice, rats, tree shrews and small primates). This paradigm is a valuable alternative for the use of a behavioral test battery, since a broad behavioral spectrum of an animal's behavioral profile can be investigated in one single test. The apparatus consists of a box, representing the 'protected' area, separated from a group compartment. A board, on which small cylinders are staggered in three lines, is placed in the center of the box, representing the 'unprotected' area of the set-up. The cognitive abilities of the animals can be measured by baiting some cylinders on the board and measuring the working and reference memory. Other unconditioned behavior, such as activity-related-, anxiety-related- and social behavior, can be observed using this paradigm. Behavioral flexibility and the ability to habituate to a novel environment can additionally be observed by subjecting the animals to multiple trials in the mHB, revealing insight into the animals' adaptive capacities. Due to testing order effects in a behavioral test battery, naïve animals should be used for each individual experiment. By testing multiple behavioral dimensions in a single paradigm and thereby circumventing this issue, the number of experimental animals used is reduced. Furthermore, by avoiding social isolation during testing and without the need to food deprive the animals, the mHB represents a behavioral test system, inducing if any, very low amount of stress. PMID:25938188

  6. Differential interactions engendered by benzodiazepine and neuroactive steroid combinations on schedule-controlled responding in rats.

    PubMed

    Gunter, Barak W; Platt, Donna M; Rowlett, James K

    2015-10-01

    Benzodiazepines are positive allosteric modulators of the GABAA receptor and are prescribed as anxiolytics, hypnotics, and anticonvulsants. While these drugs clearly have clinical value, their use is associated with unwanted side effects such as sedation and motor impairment. Neuroactive steroids are endogenous modulators of GABAA receptors and recent evidence has shown that combinations of the triazolo-benzodiazepine triazolam and the endogenous neuroactive steroid pregnanolone can produce both supra-additive anxiolytic effects and infra-additive reinforcing effects. In the present study, we investigated these same combinations as well as combinations of two clinically-relevant drugs from different chemical classes, the 1, 4 substituted (7-nitro) benzodiazepine clonazepam and the synthetic neuroactive steroid ganaxolone, in rats trained under a 10-response, fixed ratio (FR) schedule of food reinforcement. All four drugs induced a significant and dose-dependent suppression of food-maintained responding. From the dose-response functions, ED50s (i.e., the doses that engendered 50% of the maximum rate-decreasing effect) were generated for each drug. Dose-response functions for combinations of triazolam/pregnanolone, clonazepam/ganaxolone, triazolam/ganaxolone, and clonazepam/pregnanolone were then determined. Isobolographic analysis of the rate-decreasing effects of these combinations revealed that the potencies of the triazolam/pregnanolone combinations were supra-additive while the clonazepam/ganaxolone combinations were additive or infra-additive in relation to predicted values based on dose-additive effects. Furthermore, mixtures of clonazepam/pregnanolone were supra-additive while triazolam/ganaxolone combinations were additive, infra-additive and supra-additive. These results suggest that the ability of benzodiazepine and neuroactive steroid combinations to attenuate rates of food-maintained responding depends critically on both the constituent drugs and the

  7. Differential interaction of ADP-ribosylation factors 1, 3, and 5 with rat brain Golgi membranes.

    PubMed Central

    Tsai, S C; Adamik, R; Haun, R S; Moss, J; Vaughan, M

    1992-01-01

    Six mammalian ADP-ribosylation factors (ARFs) identified by cDNA cloning were expressed as recombinant proteins (rARFs) that stimulated cholera toxin ADP-ribosyltransferase activity. Microsequencing of soluble ARFs I and II (sARFs I and II), purified from bovine brain, established that they are ARFs 1 and 3, respectively. Rabbit antibodies (IgG) against sARF II reacted similarly with ARFs 1, 2, and 3 (class I) on Western blots. ARFs 1 and 3 were distinguished by their electrophoretic mobilities. Antiserum against rARF 5 cross-reacted partially with rARF 4 but not detectably with rARF 6 and minimally with class I ARFs. Guanosine 5'-O-(3-thiotriphosphate) (GTP[gamma S]) increased recovery of ARF activity and immunoreactivity in organelle fractions separated by density gradient centrifugation, after incubation of rat brain homogenate with ATP and a regenerating system. ARF 1 accumulated in microsomes plus Golgi and Golgi fractions, whereas ARF 5 seemed to localize more specifically in Golgi; the smaller increment in ARF 3 was distributed more evenly among fractions. On incubation of Golgi with a crude ARF fraction, GTP[gamma S], and an ATP-regenerating system, association of ARF activity with Golgi increased with increasing ATP concentration paralleled by increases in immunoreactive ARFs 1 and 5 and, to a lesser degree, ARF 3. Golgi incubated with GTP[gamma S] and purified ARF 1 or 3 bound more ARF 1 than ARF 3. Based on immunoreactivity and assay of ARF activity, individual ARFs 1, 3, and 5 appeared to behave independently and selectively in their GTP-dependent association with Golgi in vitro. Images PMID:1409634

  8. Differential interaction of ADP-ribosylation factors 1, 3, and 5 with rat brain Golgi membranes.

    PubMed

    Tsai, S C; Adamik, R; Haun, R S; Moss, J; Vaughan, M

    1992-10-01

    Six mammalian ADP-ribosylation factors (ARFs) identified by cDNA cloning were expressed as recombinant proteins (rARFs) that stimulated cholera toxin ADP-ribosyltransferase activity. Microsequencing of soluble ARFs I and II (sARFs I and II), purified from bovine brain, established that they are ARFs 1 and 3, respectively. Rabbit antibodies (IgG) against sARF II reacted similarly with ARFs 1, 2, and 3 (class I) on Western blots. ARFs 1 and 3 were distinguished by their electrophoretic mobilities. Antiserum against rARF 5 cross-reacted partially with rARF 4 but not detectably with rARF 6 and minimally with class I ARFs. Guanosine 5'-O-(3-thiotriphosphate) (GTP[gamma S]) increased recovery of ARF activity and immunoreactivity in organelle fractions separated by density gradient centrifugation, after incubation of rat brain homogenate with ATP and a regenerating system. ARF 1 accumulated in microsomes plus Golgi and Golgi fractions, whereas ARF 5 seemed to localize more specifically in Golgi; the smaller increment in ARF 3 was distributed more evenly among fractions. On incubation of Golgi with a crude ARF fraction, GTP[gamma S], and an ATP-regenerating system, association of ARF activity with Golgi increased with increasing ATP concentration paralleled by increases in immunoreactive ARFs 1 and 5 and, to a lesser degree, ARF 3. Golgi incubated with GTP[gamma S] and purified ARF 1 or 3 bound more ARF 1 than ARF 3. Based on immunoreactivity and assay of ARF activity, individual ARFs 1, 3, and 5 appeared to behave independently and selectively in their GTP-dependent association with Golgi in vitro. PMID:1409634

  9. Changes in gene expression and cellular localization of insulin-like growth factors 1 and 2 in the ovaries during ovary development of the yellowtail, Seriola quinqueradiata.

    PubMed

    Higuchi, Kentaro; Gen, Koichiro; Izumida, Daisuke; Kazeto, Yukinori; Hotta, Takuro; Takashi, Toshinori; Aono, Hideaki; Soyano, Kiyoshi

    2016-06-01

    A method of controlling the somatic growth and reproduction of yellowtail fish (Seriola quinqueradiata) is needed in order to establish methods for the efficient aquaculture production of the species. However, little information about the hormonal interactions between somatic growth and reproduction is available for marine teleosts. There is accumulating evidence that insulin-like growth factor (IGF), a major hormone related somatic growth, plays an important role in fish reproduction. As the first step toward understanding the physiological role of IGF in the development of yellowtail ovaries, we characterized the expression and cellular localization of IGF-1 and IGF-2 in the ovary during development. We histologically classified the maturity of two-year-old females with ovaries at various developmental stages into the perinucleolar (Pn), yolk vesicle (Yv), primary yolk (Py), secondary yolk and tertiary yolk (Ty) stages, according to the most advanced type of oocyte present. The IGF-1 gene expression showed constitutively high levels at the different developmental stages, although IGF-1 mRNA levels tended to increase from the Py to the Ty stage with vitellogenesis, reaching maximum levels during the Ty stage. The IGF-2 mRNA levels increased as ovarian development advanced. Using immunohistochemistry methods, immunoreactive IGF-1 was mainly detected in the theca cells of ovarian follicles during late secondary oocyte growth, and in part of the granulosa cells of Ty stage oocytes. IGF-2 immunoreactivity was observed in all granulosa cells in layer in Ty stage oocytes. These results indicate that follicular IGFs may be involved in yellowtail reproduction via autocrine/paracrine mechanisms. PMID:26764214

  10. Is Change in Ovary Carbon Status a Cause or a Consequence of Maize Ovary Abortion in Water Deficit during Flowering?

    PubMed

    Oury, Vincent; Caldeira, Cecilio F; Prodhomme, Duyên; Pichon, Jean-Philippe; Gibon, Yves; Tardieu, François; Turc, Olivier

    2016-06-01

    Flower or grain abortion causes large yield losses under water deficit. In maize (Zea mays), it is often attributed to a carbon limitation via the disruption of sucrose cleavage by cell wall invertases in developing ovaries. We have tested this hypothesis versus another linked to the expansive growth of ovaries and silks. We have measured, in silks and ovaries of well-watered or moderately droughted plants, the transcript abundances of genes involved in either tissue expansion or sugar metabolism, together with the concentrations and amounts of sugars, and with the activities of major enzymes of carbon metabolism. Photosynthesis and indicators of sugar export, measured during water deprivation, suggested sugar export maintained by the leaf. The first molecular changes occurred in silks rather than in ovaries and involved genes affecting expansive growth rather than sugar metabolism. Changes in the concentrations and amounts of sugars and in the activities of enzymes of sugar metabolism occurred in apical ovaries that eventually aborted, but probably after the switch to abortion of these ovaries. Hence, we propose that, under moderate water deficits corresponding to most European drought scenarios, changes in carbon metabolism during flowering time are a consequence rather than a cause of the beginning of ovary abortion. A carbon-driven ovary abortion may occur later in the cycle in the case of carbon shortage or under very severe water deficits. These findings support the view that, until the end of silking, expansive growth of reproductive organs is the primary event leading to abortion, rather than a disruption of carbon metabolism. PMID:27208256

  11. The Notch pathway regulates both the proliferation and differentiation of follicular cells in the panoistic ovary of Blattella germanica.

    PubMed

    Irles, Paula; Elshaer, Nashwa; Piulachs, Maria-Dolors

    2016-01-01

    The Notch pathway is an essential regulator of cell proliferation and differentiation during development. Its involvement in insect oogenesis has been examined in insect species with meroistic ovaries, and it is known to play a fundamental role in cell fate decisions and the induction of the mitosis-to-endocycle switch in follicular cells (FCs). This work reports the functions of the main components of the Notch pathway (Notch and its ligands Delta and Serrate) during oogenesis in Blattella germanica, a phylogenetically basal species with panoistic ovary. As is revealed by RNAi-based analyses, Notch and Delta were found to contribute towards maintaining the FCs in an immature, non-apoptotic state. This ancestral function of Notch appears in opposition to the induction of transition from mitosis to endocycle that Notch exerts in Drosophila melanogaster, a change in the Notch function that might be in agreement with the evolution of the insect ovary types. Notch was also shown to play an active role in inducing ovarian follicle elongation via the regulation of the cytoskeleton. In addition, Delta and Notch interactions were seen to determine the differentiation of the posterior population of FCs. Serrate levels were found to be Notch-dependent and are involved in the control of the FC programme, although they would appear to play no crucial role in panoistic ovary oogenesis. PMID:26763344

  12. The Notch pathway regulates both the proliferation and differentiation of follicular cells in the panoistic ovary of Blattella germanica

    PubMed Central

    Irles, Paula; Elshaer, Nashwa; Piulachs, Maria-Dolors

    2016-01-01

    The Notch pathway is an essential regulator of cell proliferation and differentiation during development. Its involvement in insect oogenesis has been examined in insect species with meroistic ovaries, and it is known to play a fundamental role in cell fate decisions and the induction of the mitosis-to-endocycle switch in follicular cells (FCs). This work reports the functions of the main components of the Notch pathway (Notch and its ligands Delta and Serrate) during oogenesis in Blattella germanica, a phylogenetically basal species with panoistic ovary. As is revealed by RNAi-based analyses, Notch and Delta were found to contribute towards maintaining the FCs in an immature, non-apoptotic state. This ancestral function of Notch appears in opposition to the induction of transition from mitosis to endocycle that Notch exerts in Drosophila melanogaster, a change in the Notch function that might be in agreement with the evolution of the insect ovary types. Notch was also shown to play an active role in inducing ovarian follicle elongation via the regulation of the cytoskeleton. In addition, Delta and Notch interactions were seen to determine the differentiation of the posterior population of FCs. Serrate levels were found to be Notch-dependent and are involved in the control of the FC programme, although they would appear to play no crucial role in panoistic ovary oogenesis. PMID:26763344

  13. Estrogen and voluntary exercise interact to attenuate stress-induced corticosterone release but not anxiety-like behaviors in female rats.

    PubMed

    Jones, Alexis B; Gupton, Rebecca; Curtis, Kathleen S

    2016-09-15

    The beneficial effects of physical exercise to reduce anxiety and depression and to alleviate stress are increasingly supported in research studies. The role of ovarian hormones in interactions between exercise and anxiety/stress has important implications for women's health, given that women are at increased risk of developing anxiety-related disorders, particularly during and after the menopausal transition. In these experiments, we tested the hypothesis that estrogen enhances the positive impact of exercise on stress responses by investigating the combined effects of exercise and estrogen on anxiety-like behaviors and stress hormone levels in female rats after an acute stressor. Ovariectomized female rats with or without estrogen were given access to running wheels for one or three days of voluntary running immediately after or two days prior to being subjected to restraint stress. We found that voluntary running was not effective at reducing anxiety-like behaviors, whether or not rats were subjected to restraint stress. In contrast, stress-induced elevations of stress hormone levels were attenuated by exercise experience in estrogen-treated rats, but were increased in rats without estrogen. These results suggest that voluntary exercise may be more effective at reducing stress hormone levels if estrogen is present. Additionally, exercise experience, or the distance run, may be important in reducing stress. PMID:27247143

  14. Adiponectin and its receptors in the ovary: further evidence for a link between obesity and hyperandrogenism in polycystic ovary syndrome.

    PubMed

    Comim, Fabio V; Hardy, Kate; Franks, Stephen

    2013-01-01

    Polycystic ovary syndrome (PCOS), characterized by ovarian androgen excess, is the commonest endocrine disorder in women. Obesity increases androgen synthesis, a phenomenon attributed to the accompanying hyperinsulinemia. Our hypothesis was that adipokines, fat cell-derived hormones, play a direct role in modulating ovarian androgen secretion. Therefore, the aims of this study were to explore the effects of adipokines (in particular, adiponectin) on ovarian steroidogenesis and compare the expression of adiponectin receptors in ovaries from women with and without PCO. Sections of archived human ovaries (nine from women with normal ovaries and 16 with PCOS, classified histologically, with reference to menstrual history and ultrasound) were analysed by quantitative morphometry and the proportion of positive-labelling cells compared. In addition, studies of androgen production in relation to adipokine function in primary bovine theca cell culture were also performed. A significantly lower proportion of theca cells expressed adiponectin receptors 1 and 2 (AdipoR1, AdipoR2) in polycystic ovaries than in normal ovaries. In cultured theca cells, adiponectin suppressed androstenedione production and gene expression of LH receptor and key enzymes in the androgen synthesis pathway. Moreover, knockdown of genes for AdipoR1 and AdipoR2 was associated with increased androstenedione secretion by bovine theca cells. These results provide evidence for a direct link between fat cell metabolism and ovarian steroidogenesis, suggesting that disruption of adiponectin and/or its receptors plays a key role in pathogenesis of hyperandrogenism in PCOS. PMID:24260388

  15. Selectivity of calcium channels in rat uterine smooth muscle: interactions between sodium, calcium and barium ions.

    PubMed

    Jmari, K; Mironneau, C; Mironneau, J

    1987-03-01

    1. Action potentials and membrane currents were recorded by means of a double sucrose-gap technique from Cs-loaded strips from pregnant rats superfused in Ca-free EGTA-containing solutions. 2. When external Ca was reduced below 1 microM in the presence of 1 mM-EGTA, step depolarizations from a holding potential close to the normal resting potential produced tetrodotoxin-resistant inward currents. These currents were suppressed after removal of external Na and blocked by a variety of Ca-channel blockers such as Mn, Co, Ni and nifedipine. 3. Inactivation of the inward Na current was studied using a double-pulse protocol. The degree of inactivation of the Na current was almost maximal for depolarizations of +50 mV. Application of stronger depolarizations did not significantly increase it and had no effect on recovery from inactivation. Similarly, increasing the duration of the conditioning pulse from 30 to 250 ms had no further effect on both amplitude and kinetics of the Na current. These results suggest that the Na current inactivation reflects a pure voltage-dependent mechanism. 4. The effects of external Ca were studied over a 10(9)-fold range in concentration. When external Ca was gradually increased from 1 nM to 1 microM, the inward Na current was reduced and finally abolished. As the external Ca was increased over 0.5 mM, inward current reappeared and increased as Ca became the charge carrier. 5. When Na was the charge carrier, external Ca was the most effective divalent cation in blocking the Ca channel with a half-blockage concentration of 0.1 microM. Addition of millimolar concentrations of Ca and Sr also reduced the Ba current while adding Ba to Ca-containing solution produced no increase in current. 6. Membrane currents in solutions containing both Ba and Ca ions were less than in solutions containing either Ca or Ba at the same concentration, suggesting that Ca channels are single-file multi-ion pores. 7. We conclude that the selectivity of uterine Ca

  16. Interaction of interstitial photodynamic therapy and interstitial hyperthermia in a rat rhabdomyosarcoma--a pilot study.

    PubMed

    Levendag, P C; Marijnissen, H P; de Ru, V J; Versteeg, J A; van Rhoon, G C; Star, W M

    1988-01-01

    Photodynamic therapy (PDT) involves the activation of photosensitizing drugs by light of appropriate wavelength. The photosensitive agent Hematoporphyrin Derivative (HPD) appears to be preferentially retained in malignant tumors; irradiation of HPD-containing tissue by light of appropriate wavelength (625 nm) and dose leads to (tumor) tissue destruction. The aim of this study is to achieve maximum tumor control probability with minimum normal tissue photosensitivity. In previous work from our laboratory it has been demonstrated that PDT has its fundamental effects on the tumor and normal tissue microcirculation. As it is well established that hyperthermia (HT) has its major effects in less well vascularized areas of the tumor, the combined modality of HT and PDT might prove to be advantageous. Moreover, suppression of sublethal damage repair by HT has been observed. To overcome the problem of poor light penetration into tissues and the high rate of recurrences following PDT with external irradiation, the combined effects of interstitial PDT with interstitial hyperthermia in a new line of animal experiments were studied in our laboratory. An experimental murine tumor (Rhabdomyosarcoma, type R-1) was transplanted in WAG/Rij rats and, after reaching an average diameter of 2 cm, the active component of HPD, that is Photofrin II, was injected intravenously in different dose schedules (5 mg/kg, 10 mg/kg). After 24 or 48 hrs the tumors were implanted with four flexible catheters, through which either light or heat could be applied. Light was obtained from an Argon-Dye laser system tuned to a wavelength of 625 nm at a dose rate of 75-100 mW per fiber to a dose level of 900 Joule from four linear light applicators. Heat (44 degrees C/30') was delivered by four 27 MHz radiofrequency antennas. Dose response relationships for PDT alone, HT alone and PDT combined with HT were established with cure as endpoint. This study showed that these two modalities, in the proper sequence

  17. Interactions between neutrophils and macrophages promote macrophage killing of rat muscle cells in vitro

    NASA Technical Reports Server (NTRS)

    Nguyen, Hal X.; Tidball, James G.

    2003-01-01

    Current evidence indicates that the physiological functions of inflammatory cells are highly sensitive to their microenvironment, which is partially determined by the inflammatory cells and their potential targets. In the present investigation, interactions between neutrophils, macrophages and muscle cells that may influence muscle cell death are examined. Findings show that in the absence of macrophages, neutrophils kill muscle cells in vitro by superoxide-dependent mechanisms, and that low concentrations of nitric oxide (NO) protect against neutrophil-mediated killing. In the absence of neutrophils, macrophages kill muscle cells through a NO-dependent mechanism, and the presence of target muscle cells causes a three-fold increase in NO production by macrophages, with no change in the concentration of inducible nitric oxide synthase. Muscle cells that are co-cultured with both neutrophils and macrophages in proportions that are observed in injured muscle show cytotoxicity through a NO-dependent, superoxide-independent mechanism. Furthermore, the concentration of myeloid cells that is necessary for muscle killing is greatly reduced in assays that use mixed myeloid cell populations, rather than uniform populations of neutrophils or macrophages. These findings collectively show that the magnitude and mechanism of muscle cell killing by myeloid cells are modified by interactions between muscle cells and neutrophils, between muscle cells and macrophages and between macrophages and neutrophils.

  18. Metabonomics Approach to Assessing the Metabolism Variation and Endoexogenous Metabolic Interaction of Ginsenosides in Cold Stress Rats.

    PubMed

    Zhang, Zhihao; Wang, Xiaoyan; Wang, Jingcheng; Jia, Zhiying; Liu, Yumin; Xie, Xie; Wang, Chongchong; Jia, Wei

    2016-06-01

    Metabolic profiling technology, a massive information provider, has promoted the understanding of the metabolism of multicomponent medicines and its interactions with endogenous metabolites, which was previously a challenge in clarification. In this study, an untargeted GC/MS-based approach was employed to investigate the urinary metabolite profile in rats with oral administration of ginsenosides and the control group. Significant changes of urinary metabolites contents were observed in the total ginsenosides group, revealing the impact of ginsenosides as indicated by the up- or down-regulation of several pathways involving neurotransmitter-related metabolites, tricarboxylic acid (TCA) cycle, fatty acids β-oxidation, and intestinal microflora metabolites. Meanwhile, a targeted UPLC-QQQ/MS-based metabonomic approach was developed to investigate the changes of urinary ginsenoside metabolites during the process of acute cold stress. Metabolic analysis indicated that upstream ginsenosides (rg1, re, and rf) increased significantly, whereas downstream ginsenosides (ck, ppd, and ppt) decreased correspondingly after cold exposure. Finally, the relationships between ginsenosides and significantly changed metabolites were investigated by correlation analysis. PMID:27150950

  19. Manganese superoxide dismutase promotes interaction of actin, S100A4 and Talin, and enhances rat gastric tumor cell invasion

    PubMed Central

    Indo, Hiroko P.; Matsui, Hirofumi; Chen, Jing; Zhu, Haining; Hawkins, Clare L.; Davies, Michael J.; Yarana, Chontida; St. Clair, Daret K.; Majima, Hideyuki J.

    2015-01-01

    It has been demonstrated that cancer cells are under high levels of oxidative stress and express high levels of Manganese superoxide dismutase (MnSOD) to protect themselves and support the anabolic metabolism needed for growth and cell motility. The aim of this study was to identify proteins that may have a correlation with invasion and redox regulation by mitochondrial reactive oxygen species (ROS). MnSOD scavenges superoxide anions generated from mitochondria and is an important regulator of cellular redox status. Oxidative posttranslational modification of cysteine residues is a key mechanism that regulates protein structure and function. We hypothesized that MnSOD regulates intracellular reduced thiol status and promotes cancer invasion. A proteomic thiol-labeling approach with 5-iodoacetamidofluorescein was used to identify changes in intracellular reduced thiol-containing proteins. Our results demonstrate that overexpression of MnSOD maintained the major structural protein, actin, in a reduced state, and enhanced the invasion ability in gastric mucosal cancer cells, RGK1. We also found that the expression of Talin and S100A4 were increased in MnSOD-overexpressed RGK1 cells. Moreover, Talin bound not only with actin but also with S100A4, suggesting that the interaction of these proteins may, in part, contribute to the invasive ability of rat gastric cancer. PMID:26236095

  20. Receptor-interacting protein kinase 3-mediated programmed cell necrosis in rats subjected to focal cerebral ischemia-reperfusion injury

    PubMed Central

    DONG, YANRU; BAO, CUIFEN; YU, JINGWEI; LIU, XIA

    2016-01-01

    In the current study, the activation of tumor necrosis factor-α receptor 1 (TNFR1) and receptor-interacting protein kinase 3 (RIP3) were investigated following cerebral ischemia-reperfusion injury (CIRI). Healthy SD rats were randomly divided into 3 groups: Sham operation group, model group and inhibitor group. The model group and inhibitor group were further divided into 4 subgroups of 6, 12, 24 and 72 h following CIRI. Using right middle cerebral artery embolization, the CIRI model was generated. To confirm that the CIRI model was established, neurological scores, TTC staining and brain water content measurements were conducted. Immunohistochemistry and western blotting were conducted to investigate the expression of TNFR1 and RIP3 in the cerebral cortex. It was observed that nerve cell necrosis occurred following 6 h of CIRI. The appearance of necrotic cells was gradually increased with increasing CIRI duration. TNFR1 and RIP3 were positively expressed following 6 h of CIRI. With increasing durations of CIRI, the protein expression levels of TNFR1 and RIP3 were significantly increased. Pre-administration with Z-VAD-FMK (zVAD) significantly increased the protein level of RIP3, however, had no effect on the levels of TNFR1, and was accompanied by a reduction in necrosis. In conclusion, RIP3-mediated cell necrosis was enhanced by caspase blockade zVAD and the function of zVAD was independent of TNFR1 signaling following IR. PMID:27220678

  1. The antiovulatory potential of progesterone antagonists correlates with a down-regulation of progesterone receptors in the hypothalamus, pituitary and ovaries.

    PubMed

    Donath, J; Nishino, Y; Schulz, T; Michna, H

    2000-03-01

    These studies analyze the regulation of progesterone receptors (PRs) in central and peripheral tissues with the aim of further understanding mechanistically the inhibition of ovulation by progesterone antagonists (PA). Therefore, it was of interest to investigate the influence of the progesterone receptor antagonist, Onapristone (ON), on PRs in the ovary, pituitary (PT), and hypothalamus (HYP), since ON effectively inhibits ovulation in rats. For this study PMSG/hCG-primed immature and adult female rats were treated with ON. Immunohistochemistry was used for the detection of PRs. Progesterone (P4) and estradiol (E2) levels were determined by RIA. PR expression in the ovaries of immature rats was not detectable until after hCG administration. In these animals, ON caused a reduction in the staining intensity of PR in the tertiary follicles at the time when the preovulatory P4-surge was inhibited (6 h post hCG). Adult rats treated for 15 days with ON showed a decreased PR expression in PT and HYP. At this time (proestrus, 7 p.m.) the P4 and E2 levels are significantly lowered. These results suggest that after treatment with ON the expression of PR is reduced in the ovary, PT and HYP. The regulation of PR in the ovary seems to be less dependent on estrogens than on LH. Thus, it is conceivable that the reduced PR expression after ON treatment may be a result of decreased LH sensitivity in the ovary. In the pituitary and hypothalamus, PR expression is stimulated by estrogens and progesterone, and therefore the fall in the P4 and E2 levels in ON-treated animals may be responsible for the reduced PR expression in PT and HYP, and may contribute to the antiovulatory effect of ON. We therefore conclude that the mechanism of the antiovulatory potency of progesterone antagonists is based on a reduced preovulatory P4-production and PR expression in the ovary and also on the down-regulation of PR in the anterior pituitary and hypothalamus. PMID:10755181

  2. The osmoreceptor complex in the rat: evidence for interactions between the supraoptic and other diencephalic nuclei.

    PubMed

    Honda, K; Negoro, H; Dyball, R E; Higuchi, T; Takano, S

    1990-12-01

    1. Experiments were undertaken to provide evidence for the existence of a circuit of neuronal interconnections between the supraoptic nucleus (SON), the ventral anteroventral third ventricular region (including the organum vasculosum of the lamina terminalis; ventral AV3V) and the median preoptic nucleus (MnPO), and to determine the importance of these connections in the osmotic control of the neuronal activity of the SON. Extracellular recordings were made in the urethane-anaesthetized male rat from neurones in one of these three sites, while the other two sites were electrically stimulated. 2. During recording from the SON, electrical stimulus pulses applied either to the ventral AV3V or to the MnPO were followed by orthodromic excitation (OD+) or initial short-duration inhibition followed by long-duration excitation (OD- +) of most SON neurones (44/48). The latency of OD+ or OD+ component of OD- + response produced by electrical stimulation of the MnPO was significantly (paired t test, P less than 0.01) shorter than that by the stimulation of the ventral AV3V. None of the neurones we recorded in the SON was activated antidromically by stimulation of either the ventral AV3V or the MnPO. Pressure injection of lidocaine (10%, 50 nl) into the MnPO reversibly depressed the OD+ effect after stimulation of the ventral AV3V in all the SON neurones tested (11/11), while injection of lidocaine into the ventral AV3V did not affect the OD+ effect after stimulation of the MnPO in most neurones (7/9). Both types of observation are consistent with the presence of an excitatory input to SON through the MnPO. 3. Pressure injection of lidocaine into both the ventral AV3V and the MnPO reversibly blocked the activation of SON neurones following an I.P. injection of 1.5 M-NaCl (1 ml) (ventral AV3V 11/11; MnPO, 10/10 cells tested). Injection of lidocaine at both sites, however, did not prevent activation of SON neurones by hypovolaemia (2 ml of blood was withdrawn through a cannula

  3. Endogenous fluorescence emission of the ovary

    NASA Astrophysics Data System (ADS)

    Utzinger, Urs; Kirkpatrick, Nathaniel D.; Drezek, Rebekah A.; Brewer, Molly A.

    2005-03-01

    Epithelial ovarian cancer has the highest mortality rate among the gynecologic cancers. Early detection would significantly improve survival and quality of life of women at increased risk to develop ovarian cancer. We have constructed a device to investigate endogenous signals of the ovarian tissue surface in the UV C to visible range and describe our initial investigation of the use of optical spectroscopy to characterize the condition of the ovary. We have acquired data from more than 33 patients. A table top spectroscopy system was used to collect endogenous fluorescence with a fiberoptic probe that is compatible with endoscopic techniques. Samples were broken into five groups: Normal-Low Risk (for developing ovarian cancer) Normal-High Risk, Benign, and Cancer. Rigorous statistical analysis was applied to the data using variance tests for direct intensity versus diagnostic group comparisons and principal component analysis (PCA) to study the variance of the whole data set. We conclude that the diagnostically most useful excitation wavelengths are located in the UV. Furthermore, our results indicate that UV B and C are most useful. A safety analysis indicates that UV-C imaging can be conducted at exposure levels below safety thresholds. We found that fluorescence excited in the UV-C and UV-B range increases from benign to normal to cancerous tissues. This is in contrast to the emission created with UV-A excitation which decreased in the same order. We hypothesize that an increase of protein production and a decrease of fluorescence contributions of the extracellular matrix could explain this behavior. Variance analysis also identified fluctuation of fluorescence at 320/380 which is associated with collagen cross link residues. Small differences were observed between the group at high risk and normal risk for ovarian cancer. High risk samples deviated towards the cancer group and low risk samples towards benign group.

  4. Ovarian Aging-Like Phenotype in the Hyperandrogenism-Induced Murine Model of Polycystic Ovary

    PubMed Central

    Rezvanfar, Mohammad Amin; Shojaei Saadi, Habib A.; Gooshe, Maziar; Abdolghaffari, Amir Hosein; Baeeri, Maryam; Abdollahi, Mohammad

    2014-01-01

    There are prominently similar symptoms, effectors, and commonalities in the majority of characteristics between ovarian aging and polycystic ovarian syndrome (PCOS). Despite the approved role of oxidative stress in the pathogenesis of PCOS and aging, to our knowledge, the link between the PCO(S) and aging has not been investigated yet. In this study we investigated the possible exhibition of ovarian aging phenotype in murine model of PCO induced by daily oral administration of letrozole (1 mg/kg body weight) for 21 consecutive days in the female Wistar rats. Hyperandrogenization showed irregular cycles and histopathological characteristics of PCO which was associated with a significant increase in lipid peroxidation (LPO) and reactive oxygen species (ROS) and decrease in total antioxidant capacity (TAC) in serum and ovary. Moreover, serum testosterone, insulin and tumor necrosis factor-alpha (TNF-α) levels, and ovarian matrix metalloproteinase-2 (MMP-2) were increased in PCO rats compared with healthy controls, while estradiol and progesterone diminished. Almost all of these findings are interestingly found to be common with the characteristics identified with (ovarian) aging showing that hyperandrogenism-induced PCO in rat is associated with ovarian aging-like phenotypes. To our knowledge, this is the first report that provides evidence regarding the phenomenon of aging in PCO. PMID:24693338

  5. Ovarian aging-like phenotype in the hyperandrogenism-induced murine model of polycystic ovary.

    PubMed

    Rezvanfar, Mohammad Amin; Shojaei Saadi, Habib A; Gooshe, Maziar; Abdolghaffari, Amir Hosein; Baeeri, Maryam; Abdollahi, Mohammad

    2014-01-01

    There are prominently similar symptoms, effectors, and commonalities in the majority of characteristics between ovarian aging and polycystic ovarian syndrome (PCOS). Despite the approved role of oxidative stress in the pathogenesis of PCOS and aging, to our knowledge, the link between the PCO(S) and aging has not been investigated yet. In this study we investigated the possible exhibition of ovarian aging phenotype in murine model of PCO induced by daily oral administration of letrozole (1 mg/kg body weight) for 21 consecutive days in the female Wistar rats. Hyperandrogenization showed irregular cycles and histopathological characteristics of PCO which was associated with a significant increase in lipid peroxidation (LPO) and reactive oxygen species (ROS) and decrease in total antioxidant capacity (TAC) in serum and ovary. Moreover, serum testosterone, insulin and tumor necrosis factor-alpha (TNF-α) levels, and ovarian matrix metalloproteinase-2 (MMP-2) were increased in PCO rats compared with healthy controls, while estradiol and progesterone diminished. Almost all of these findings are interestingly found to be common with the characteristics identified with (ovarian) aging showing that hyperandrogenism-induced PCO in rat is associated with ovarian aging-like phenotypes. To our knowledge, this is the first report that provides evidence regarding the phenomenon of aging in PCO. PMID:24693338

  6. Cardiometabolic Effects of Chronic Hyperandrogenemia in a New Model of Postmenopausal Polycystic Ovary Syndrome.

    PubMed

    Dalmasso, Carolina; Maranon, Rodrigo; Patil, Chetan; Bui, Elizabeth; Moulana, Mohadetheh; Zhang, Howei; Smith, Andrew; Yanes Cardozo, Licy L; Reckelhoff, Jane F

    2016-07-01

    Postmenopausal women who have had polycystic ovary syndrome (PCOS) and chronic hyperandrogenemia may be at a greater risk for cardiovascular disease than normoandrogenemic postmenopausal women. The cardiometabolic effect of chronic hyperandrogenemia in women with PCOS after menopause is unclear. The present study was performed to test the hypothesis that chronic hyperandrogenemia in aging female rats would have more deleterious effects on metabolic function, blood pressure, and renal function than in normoandrogenemic age-matched females. Female Sprague Dawley were implanted continuously, beginning at 4-5 weeks, with dihydrotestosterone (postmenopausal hyperandrogenemic female [PMHAF]) or placebo pellets (controls), and were studied at 13 months of age. Plasma DHT was 3-fold higher, and estradiol was 90% lower in PMHAF than controls. Body weights