scholarly journals Delayed Neuroendocrine Sexual Maturation in Female Rats After a Very Low Dose of Bisphenol A Through Altered GABAergic Neurotransmission and Opposing Effects of a High Dose

Endocrinology ◽  
2016 ◽  
Vol 157 (5) ◽  
pp. 1740-1750 ◽  
Author(s):  
Delphine Franssen ◽  
Arlette Gérard ◽  
Benoit Hennuy ◽  
Anne-Françoise Donneau ◽  
Jean-Pierre Bourguignon ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Sexual Maturation ◽  
Low Dose ◽  
Ex Vivo ◽  
Female Rats ◽  
High Dose ◽  
Sequencing Analysis ◽  
Female Rat ◽  
Vaginal Opening ◽  
Gabaergic Neurotransmission

Abstract Rat sexual maturation is preceded by a reduction of the interpulse interval (IPI) of GnRH neurosecretion. This work aims at studying disruption of that neuroendocrine event in females after early exposure to a very low dose of bisphenol A (BPA), a ubiquitous endocrine disrupting chemical. Female rats were exposed to vehicle or BPA 25 ng/kg·d, 25 μg/kg·d, or 5 mg/kg·d from postnatal day (PND)1 to PND5 or PND15. Exposure to 25 ng/kg·d of BPA for 5 or 15 days was followed by a delay in developmental reduction of GnRH IPI studied ex vivo on PND20. After 15 days of exposure to that low dose of BPA, vaginal opening tended to be delayed. In contrast, exposure to BPA 5 mg/kg·d for 15 days resulted in a premature reduction in GnRH IPI and a trend toward early vaginal opening. RNA sequencing analysis on PND20 indicated that exposure to BPA resulted in opposing dose effects on the mRNA expression of hypothalamic genes involved in gamma aminobutyric acid A (GABAA) neurotransmission. The study of GnRH secretion in vitro in the presence of GABAA receptor agonist/antagonist confirmed an increased or a reduced GABAergic tone after in vivo exposure to the very low or the high dose of BPA, respectively. Overall, we show for the first time that neonatal exposure to BPA leads to opposing dose-dependent effects on the neuroendocrine control of puberty in the female rat. A very low and environmentally relevant dose of BPA delays neuroendocrine maturation related to puberty through increased inhibitory GABAergic neurotransmission.

ANDROGENIZATION OF THE NEONATAL FEMALE RAT WITH VERY LOW DOSES OF ANDROGEN

1973 ◽  
Vol 57 (1) ◽  
pp. 33-45 ◽  
Author(s):  
P. J. SHERIDAN ◽  
M. X. ZARROW ◽  
V. H. DENENBERG
Keyword(s):  
Low Dose ◽  
Physiological Effect ◽  
Neonatal Rat ◽  
Female Rats ◽  
High Dose ◽  
Female Rat ◽  
Low Doses ◽  
Minimal Effective Dose ◽  
High Doses ◽  
Long Acting

SUMMARY The administration of a high dose of androgen on a single day to a neonatal female rat has been shown repeatedly to induce persistent vaginal cornification (PVC). However, this type of treatment does not parallel the continuous androgen secretion present in the male, and the high doses that have been used could represent a pharmacological and not a physiological effect. Experiments were carried out to determine the minimal effective dose of testosterone propionate (TP) needed to cause PVC when the androgen is administered to the neonatal rat for the first 10 days of life or as a long-acting ester. Injection of 1, 3 or 9 μg TP on days 1–10 of life in female rats induced PVC in adulthood. All three doses were found to be more effective than a testicular transplant on day 1. In female rats injected with low doses of TP twice daily for the first 10 days of life, PVC was shown between 90 and 100 days of life in 21 out of 22 animals given 0·5 μg TP/injection, and in eight out of 22 animals given 0·05 μg TP/injection. In an experiment where female rats were given a single injection of 0·1, 1·0 or 10·0 μg TP, or 0·1 or 1·0 μg testosterone cyclopentylpropionate (TC, a long-acting androgen) on the first day after birth, PVC occurred at 90–100 days of age in 15 of the 18 animals which were injected with 10 μg TP, in none of the 17 animals which were injected with 1 μg TP, and in 10 of 11 animals which were injected with 1 μg TC. The effects of all treatments on vaginal opening, first oestrus, ovarian weight, body weight and sexual behaviour are reported. The use and implications of low dose regimens are discussed in relation to the construction of an experimental model for the study of sexual differentiation.

scholarly journals Neonatal exposure to bisphenol A modifies the abundance of estrogen receptor α transcripts with alternative 5′-untranslated regions in the female rat preoptic area

2007 ◽  
Vol 194 (1) ◽  
pp. 201-212 ◽  
Author(s):  
Lucas Monje ◽  
Jorgelina Varayoud ◽  
Enrique H Luque ◽  
Jorge G Ramos
Keyword(s):  
Estrogen Receptor ◽  
Bisphenol A ◽  
Low Dose ◽  
Preoptic Area ◽  
Methylation Status ◽  
Estrogen Receptor Α ◽  
Female Rats ◽  
Untranslated Regions ◽  
Neonatal Exposure ◽  
High Dose

The xenoestrogen bisphenol A (BPA) is commonly ingested by humans. We examined the effects of neonatal exposure to low versus high doses of BPA over the control of estrogen receptor α (ERα) expression in the preoptic area (POA) of prepubertal female rats. Pups received s.c. injections every 48 h of BPA (high dose, 20 mg/kg and low dose, 0.05 mg/kg) or diethylstilbestrol (DES, 0.02 mg/kg) from postnatal day (PND) 1 to PND7 and were killed at PND8 or PND21. Relative expression of ERα transcripts containing alternative 5′-untranslated regions OS, ON, O, OT, and E1 in POA were evaluated by RT-PCR. Methylation status of ERα promoters was determined by bisulfited DNA restriction analysis and ERα protein by immunohistochemistry. In PND8, the high dose of BPA and DES diminished total ERα mRNA levels, mediated by the decreased expression of ERα-O and ERα-OT variants. In contrast, the low dose of BPA augmented total ERα mRNA by increasing the expression of the ERα-E1 variant. In PND21, both BPA doses increased total ERα mRNA by means of the augmented expression of ERα-O and ERα-OT variants. In PND21, the methylation status of the ERα promoters and the circulating levels of estradiol were similar in all experimental groups. At PND8 and PND21, DES and the high dose of BPA decreased, while the low dose of BPA increased ERα protein in the POA. These findings show that neonatal BPA exposure alters the abundance of hypothalamic ERα transcript variants and protein in a dose-dependent manner.

RETARDATION OF FIRST OVULATION IN PUBERTAL RATS AFTER TREATMENT WITH 5α-ANDROSTANE-3α,17β-DIOL OR ITS 3β-EPIMER

1982 ◽  
Vol 92 (1) ◽  
pp. 31-35 ◽  
Author(s):  
P. KRAMER ◽  
H. M. A. MEIJS-ROELOFS
Keyword(s):  
Body Weight ◽  
Precocious Puberty ◽  
Sexual Maturation ◽  
Female Rats ◽  
Female Rat ◽  
Vaginal Opening ◽  
Significant Delay ◽  
Vaginal Smears ◽  
Immature Female ◽  
High Doses

The effect was studied of five daily injections of 50 μg of either 5α-androstane-3α,17β-diol (3α-androstanediol) or its 3β-epimer (3β-androstanediol), starting on day 22 of life, on sexual maturation in female rats. No difference was found in the age and body weight at first oestrus between oil-treated rats and rats treated with either 3α- or 3β-androstanediol. The only difference observed between these groups consisted of the occurrence of a 'pinhole' vaginal opening a few days before oestrus in 50% of the steroid-treated rats; in oil-treated rats immediate full vaginal opening and first oestrus coincided in ten out of 12 rats. Different effects were obtained when the higher dose of 100 μg daily was used; effects were dissimilar in rats treated with 3α- and 3β-androstanediol. If administration of the higher dose of 3β-androstanediol was started on day 22 and continued until the day of full vaginal opening and first oestrus, a significant delay of this first oestrus, preceded by a few days of a 'pinhole' type of vaginal opening, was observed. After administration of the higher dose of 3α-androstanediol a 'pinhole' type of vaginal opening, accompanied by dioestrous-like vaginal smears, was also found, but oestrus did not occur during the period when injections were given. After the injections were stopped on day 45, first oestrus developed within 6 days in all rats. The previous findings of others that administration of 3β-androstanediol to the immature female rat may induce precocious puberty (i.e. precocious vaginal opening and first ovulation) were not confirmed in the present study. Our results indicate that high doses of free 3α-androstanediol, and to a lesser degree 3β-androstanediol, may even delay first ovulation in the rat. A possible interference of 3α-androstanediol with the triggering of the first ovulatory gonadotrophin peaks is discussed.

Benefit/Risk Profile of Combined Antiplatelet Therapy with Ticlopidine and Aspirin

1991 ◽  
Vol 65 (05) ◽  
pp. 504-510 ◽  
Author(s):  
Raffaele De Caterina ◽  
Rosa Sicari ◽  
Walter Bernini ◽  
Guido Lazzerini ◽  
Giuliana Buti Strata ◽  
...  
Keyword(s):  
Platelet Function ◽  
Low Dose ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Stable Coronary Artery Disease ◽  
High Dose ◽  
Single Drug ◽  
Before And After ◽  
Serum Thromboxane ◽  
Artery Disease

SummaryTiclopidine (T) and aspirin (ASA) are two antiplatelet drugs both capable of prolonging bleeding time (BT), with a different mechanism of action. A synergism in BT prolongation has been reported and is currently considered an argument for not recommending their combination. However, a profound suppression of platelet function might be a desirable counterpart of a marked prolongation of BT, with a possible use in selected clinical situations. We therefore studied ex vivo platelet function (aggregation by ADP 0.5-1-2.5 μM; adrenaline 0.75-2.5 μM; collagen 1.5-150 μg/ml; arachidonic acid 1 mM; PAF 1 μM; adrenaline 0.17 μM + ADP 0.62 μM; serum thromboxane ([TX]B2 generation) and BT (Mielke) in 6 patients with stable coronary artery disease receiving such combination. Patients underwent sequential laboratory evaluations at baseline, after 7 days of T 250 mg b.i.d., before and after the intravenous administration of ASA 500 mg, respectively, and, finally, after a minimum of 7 days of sole ASA oral administration (50 mg/day). The experimental design, therefore, allowed a comparison of T and ASA effects (2nd and 4th evaluation), and an assessment of the combination effect (3rd evaluation). Platelet aggregation in response to all doses of ADP was depressed more by T than by ASA. Conversely, responses to adrenaline, and arachidonate were affected more by ASA than by T. For all other agents, differences were not significant. T + ASA combination was more effective (p <0.05) than either treatment alone in depressing responses to high-dose collagen (% over control, mean ± SEM: T: 95 ± 3; ASA: 96 ± 5; T + ASA: 89 ± 4). Serum TXB2 (basal, ng/ml: 380 ± 54) did not change with T (372 ± 36), dropped to <1 ng/ml on ASA injection and slightly re-increased to 9.1 ± 3.1 ng/ml on oral low-dose ASA. BT (basal 7.4 ± 0.6 min) was affected similarly by T (9.2 ± 0.8) or ASA (9.7 ± 0.9) alone, but increased to 15.0 ± 0.7 min on combination treatment (106% increase over control). Thus, the strong synergism in BT prolongation by ASA-T combination has a counterpart in the inhibition of platelet function in response to strong stimuli such as high-dose collagen, not otherwise affected significantly by single-drug treatment. This effect is a possible rationale for the clinical evaluation of T + ASA combination.

Exteroceptive Factors, Sexual Maturation and Reproduction in the Female Rat

1979 ◽  
Vol 13 (3) ◽  
pp. 283-286 ◽  
Author(s):  
M. L. Norris ◽  
C. E. Adams
Keyword(s):  
Reproductive Performance ◽  
Sexual Maturation ◽  
Sexual Maturity ◽  
Mature Male ◽  
Female Rat ◽  
Vaginal Opening ◽  
Sexually Mature

Summary Keeping a sexually mature male with a weanling female rat advanced neither the time of vaginal opening nor that of 1st oestrus. In 2 of 3 experiments females kept singly after weaning reached sexual maturity significantly earlier than did grouped females. The reproductive performance of females mated at 1st oestrus was not significantly different from that of older primiparae. 26 rats gave birth to an average of 9·3 young at 59·5 days of age, and 22 of them reared 96% of the young to weaning.

Male gender increases sensitivity to renal injury in response to cholesterol loading

2003 ◽  
Vol 284 (4) ◽  
pp. F718-F726 ◽  
Author(s):  
Diana M. Attia ◽  
Roel Goldschmeding ◽  
Mahmoud A. Attia ◽  
Peter Boer ◽  
Hein A. Koomans ◽  
...  
Keyword(s):  
Renal Injury ◽  
Low Dose ◽  
Plasma Cholesterol ◽  
A Priori ◽  
No Synthase ◽  
Male Gender ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Cholesterol Feeding

Males are at greater risk for renal injury than females. This may relate to nitric oxide (NO) availability, because female rats have higher renal endothelial NO synthase (NOS) levels. Previously, our laboratory found susceptibility to proteinuria induced by NOS inhibition in male compared with female rats. Dyslipidemia and hypercholesterolemia dose dependently decreased renal NOS activity and caused renal injury in female rats. We hypothesized that exposure of male rats to hypercholesterolemia would lead to more renal injury in male than in female rats due to an a priori lower renal NO system. Female and male rats were fed no, low-dose, or high-dose cholesterol for 24 wk. Cholesterol feeding dose dependently increased proteinuria in both female and male rats, but male rats developed more proteinuria at similar plasma cholesterol ( P < 0.001). Control males had lower renal NOS activity than control females (4.44 ± 0.18 vs. 7.46 ± 0.37 pmol · min−1 · mg protein−1; P < 0.05), and cholesterol feeding decreased renal NOS activity in males and in females ( P < 0.05). Cholesterol-fed males developed significantly more vascular, glomerular, and tubulointerstitial monocyte/macrophage influx and injury than females. Thus under baseline conditions, male rats have lower renal NOS activity than female rats. This may explain why male rats are more sensitive to renal injury by factors that decrease NO availability, such as hypercholesterolemia.

Investigation of the effects of bisphenol-A exposure on lymphoid system in prenatal stage

2020 ◽  
Vol 36 (7) ◽  
pp. 502-513
Author(s):  
Işil Aydemir ◽  
Caner Özbey ◽  
Oktay Özkan ◽  
Şadiye Kum ◽  
Mehmet İbrahim Tuğlu
Keyword(s):  
Lymph Node ◽  
Bisphenol A ◽  
Tissue Damage ◽  
Corn Oil ◽  
Histopathological Examination ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Organ Function ◽  
Pregnant Rats

Bisphenol-A (BPA) used in the production of plastic materials is a temperature-soluble agent. It also has a steroid hormone-like activity; therefore, it poses a danger to human health. In our study, we aimed to investigate the effects of BPA on lymph node and spleen in male rats exposed to this agent during prenatal stage. The pregnant female rats were divided into four groups: control, sham, low dose (300 µg/kg BPA), and high dose (900 µg/kg BPA). BPA was dissolved in 1 mL of corn oil and administered to the pregnant rats every day during pregnancy. On the 21st and 45th day after the birth, male rats’ lymph node and spleen samples were taken and histopathological examination was performed. Samples were stained with hematoxylin and eosin to determine the general histological appearance, and with CD3 and CD20 immunohistochemically. The results of staining were evaluated by H-score, and statistical analysis was performed. In the samples, BPA applications were not found to cause significant tissue damage. But there was a significant decrease in the immunoreactivities of CD3 and CD20 after BPA applications in both 21st and 45th day samples. After high dose BPA administration, decreased CD3 immunoreactivity was statistically significant. It is thought that BPA does not cause histologically significant tissue damage, but it may impair organ function at cellular level. The investigation of molecules involved in organ function will be useful in revealing the mechanisms that will cause dysfunction.

scholarly journals Comparative effects of testosterone propionate, oestradiol benzoate, ICI 182,780, tamoxifen and raloxifene on hypothalamic differentiation in the female rat

2002 ◽  
Vol 172 (3) ◽  
pp. 441-448 ◽  
Author(s):  
L Pinilla ◽  
ML Barreiro ◽  
LC Gonzalez ◽  
M Tena-Sempere ◽  
E Aguilar
Keyword(s):  
Positive Feedback ◽  
Testosterone Propionate ◽  
Reproductive Function ◽  
Female Rats ◽  
Normal Brain ◽  
Female Rat ◽  
Vaginal Opening ◽  
Ici 182,780 ◽  
Oestradiol Benzoate ◽  
Normal Differentiation

Hypothalamic differentiation in the female rat during the neonatal period is critically dependent on the steroid milieu, as permanent changes in reproductive function are observed after administration of oestradiol and testosterone during such a critical stage. Selective oestrogen modulators (SERMs) constitute a family of drugs that, depending on the tissue, are able to exert oestrogenic or antioestrogenic actions. The present experiments were conducted to analyse whether the SERMs, tamoxifen and raloxifene, can cause oestrogenic actions during the hypothalamic differentiation period. Postnatal female rats were injected between days 1 and 5 with 100 microg/day tamoxifen, raloxifene or ICI 182,780 (a pure antioestrogen). Other groups of animals were injected on day 1 of age with 100 microg oestradiol benzoate (OeB) or 1.25 mg testosterone propionate (TP) alone or in combination with raloxifene (500 microg/day between days 1 and 5). In all experimental groups, the age, body weight and concentrations of serum gonadotrophins at vaginal opening were recorded, whereas vaginal cyclicity and the negative and positive feedback between oestradiol and LH were monitored in adulthood. The results obtained confirmed the ability of high doses of OeB or TP to alter the normal differentiation of the brain permanently. They also reinforced the hypothesis that oestrogens are also necessary for normal brain differentiation in female rats because administration of a pure antioestrogen, such as ICI 182,780 permanently altered the function of the reproductive axis. In addition, our data provided evidence for different actions of the two SERMs under analysis (raloxifene and tamoxifen) upon peripheral targets, as raloxifene advanced vaginal opening whereas tamoxifen did not. In contrast, their actions on brain differentiation appeared similar and analogous to those obtained after neonatal administration of oestradiol, as evidenced by vaginal acyclicity, ovarian atrophy, sterility and abolition of negative and positive feedback between oestradiol and LH, thus suggesting an oestrogenic action of these SERMs on hypothalamic differentiation. Moreover, the oestrogenic activity of raloxifene was supported by its inability to block the effects of OeB and TP administered neonatally. In conclusion, the present results indicated that the SERMs, tamoxifen and raloxifene, exert an oestrogen-like effect upon hypothalamic differentiation of the neonatal female rat.

scholarly journals Attenuation of Thrombosis by Crude Rice (Oryza sativa) Bran Policosanol Extract:Ex VivoPlatelet Aggregation and Serum Levels of Arachidonic Acid Metabolites

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Wai-Teng Wong ◽  
Maznah Ismail ◽  
Eusni Rahayu Mohd Tohit ◽  
Rasedee Abdullah ◽  
Yi-Da Zhang
Keyword(s):  
Platelet Aggregation ◽  
Rice Bran ◽  
Low Dose ◽  
Ex Vivo ◽  
Vascular Occlusion ◽  
Full Blood Count ◽  
Tween 20 ◽  
High Dose ◽  
Sprague Dawley ◽  
Coagulation Time

Background. Vascular occlusion or thrombosis was often attributed to uncontrolled platelet activation. Influence of sugarcane policosanol extract on platelet was reported but little was known of rice bran policosanol, particularly its mechanisms of actions on platelet activities.Objective. Antiplatelet mechanisms of rice bran policosanol extract (RBE) were studied using hyperlipidemic Sprague Dawley rats.Ex vivoplatelet aggregation, platelet count (PC), bleeding time (BT), and coagulation time were assayed. Serum eicosanoids and other aggregation-related metabolites levels were quantified.Design. Rats were divided into 6 groups for comparisons (vehicle control Tween 20/H2O, high dose policosanol 500 mg/kg, middle dose policosanol 250 mg/kg, low dose policosanol 100 mg/kg, and positive control aspirin 30 mg/kg).Results. Low dose 100 mg/kg of RBE inhibited aggregation by42.32±4.31% and this was comparable with the effect of 30 mg/kg aspirin,43.91±5.27%. Results showed that there were no significant differences in PC, BT, and coagulation time among various groups after RBE treatment. Serum thromboxane A2was attenuated while prostacyclin level increased upon RBE treatment.Conclusions. RBE reducedex vivoADP-induced platelet aggregation without giving adverse effects. No changes in full blood count suggested that rice bran policosanol did not disturb biological blood cell production and destruction yet it reduced aggregation through different mechanisms.

Effect of anterior and posterior hypothalamic lesions on precocious sexual maturation

1964 ◽  
Vol 206 (4) ◽  
pp. 805-810 ◽  
Author(s):  
Raul C. Schiavi
Keyword(s):  
Sexual Maturation ◽  
Female Rats ◽  
Vaginal Opening ◽  
Uterine Weight ◽  
Comparative Effect ◽  
Hypothalamic Lesions ◽  
Medial Hypothalamus ◽  
Show Evidence ◽  
The Brain ◽  
Made In

The comparative effect of anterior and posterior hypothalamic lesions on the development of sexual maturation of prepubertal female rats was investigated. Lesions by electrocoagulation were made in the medial hypothalamus of 45 rats at 25–26 days of age. Thirty-nine animals of the same age constituted the sham-operated and nonoperated controls. A hastened appearance of vaginal opening and first estrus, a significant increase in uterine weight, precocious ovarian luteinization, and premature sexual cycles were observed following both types of lesions. Sham-operated rats and animals with lesions in other parts of the brain did not show evidence of precocious sexual maturation.

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