Plasma Estrogen Concentrations Research Articles

Special Considerations in the Management of Women with Epilepsy in Reproductive Years.

Anti-seizure medications (ASMs) fail to prevent seizure recurrence in more than 30% of patients with epilepsy. The treatment is more difficult in premenopausal women with epilepsy (WWE) because changes in plasma estrogen and progesterone concentrations during the menstrual cycle often affect seizure frequency and intensity. Interactions between enzyme-inducin ASMs and hormonal contraceptives can lead to both a loss of seizure control and failure of contraception. Significant changes in the function of the liver and kidneys during pregnancy can accelerate metabolism and elimination of ASMs, causing breakthrough seizures. In addition, the teratogenic, cognitive, and psychological effects of ASMs on potential offspring have to be considered when choosing the best ASM regimen. Therefore, aspecialized approach is necessary for the treatment of premenopausal WWE.

Effects of Bacillus subtilis on Production Performance, Bone Physiological Property, and Hematology Indexes in Laying Hens.

Simple SummaryDue to breeding for high egg production, laying hens are at great risk for developing osteoporosis. To develop an effective feed additive for reducing the bone damage and associated pain and economic loss has become a critical issue affecting the poultry industry. The aim of this study was to investigate the effects of Bacillus subtills as a feed supplement on production performance and bone pathophysiological characteristics of laying hens. The results showed that Bacillus subtilis increases marketable eggs, protects bone health, changes the distribution of phosphorus between blood and bone, and increases estrogen but decreases interleukin-1 and tumor necrosis factor-α concentrations in blood. Results indicate that Bacillus subtilis can be used as a dietary supplement to increase marketable egg production and bone health of laying hens by inhibiting gut and systemic inflammation via the microbiota-gut-immune and the microbiota-gut-bone axes.This study was to investigate the effects of Bacillus subtilis on production performance and bone pathophysiological characteristics of layers. Twenty-four 48-week-old Lohmann Pink-shell laying hens were randomly divided into two groups: a basic diet (control) and the basic diet mixed with Bacillus subtilis (0.5 g/kg) for a 60-day trial. Statistically, independent-sample t-test was used to assess the treatment differences. The results showed that Bacillus subtilis supplementation improved the percent of marketable eggs (p < 0.05) with reduced numbers of broken and soft-shelled eggs but had no effects on egg weight, height of albumen, yolk color, and Haugh unit (p > 0.05). Bacillus subtilis supplement also elevated maximum load (p = 0.06), maximum stress (p = 0.01), stiffness (p < 0.01), and Young’s modulus (p < 0.01) but suppressed maximum strain (p = 0.06) in the femur. In addition, compared with control birds, phosphorous concentration (p < 0.01) was reduced in serum at day 61 but increased in the femur (p < 0.05) in Bacillus subtilis fed birds. Bacillus subtilis fed birds also had lower magnesium concentrations in both femur (p = 0.04) and feces (p = 0.09). Furthermore, Bacillus subtilis increased plasma estrogen concentration (p = 0.01) and femur TNF receptor superfamily member 11b (OPG) expression (p < 0.05) but reduced plasma IL-1 (p < 0.01) and TNF-α (p < 0.01) concentrations. These results indicate that Bacillus subtilis could be used as a health promotor to reduce overproduction-induced inflammation and associated bone damage and to increase marketable egg production. The data provide evidence for developing a management strategy to use Bacillus subtilis as a feed additive to improve marketable egg production and health and welfare status of laying hens.

Effects of dietary fiber supplementation in gestation diets on sow performance, physiology and milk composition for successive three parities

The experiment was conducted to evaluate the effects of dietary fiber supplementation in gestation diets on sow performance, physiology and milk composition for three successive parities. Thirty gilts were assigned randomly to two groups, and fed a basal diet [CON group; 1.10 % soluble fiber (SF), 9.14 % insoluble fiber (ISF)] or a basal diet supplemented with 22.60 g/kg inulin and 181.60 g/kg cellulose [high-fiber (HF) group] during gestation period. The gestation diets provided to sows for three successive cycles averaged 2.28 kg/d from 1 to 112 d for the CON group; and corresponding values for the HF group were 2.75 kg. During lactation and empty, all sows were fed ad libitum a standard lactation diet. Sow body weight (BW) and backfat thickness, litter size and weight, parturition progress, placental weight and lactation feed intake were recorded. In parity 3, plasma samples were collected at gestation day 110 and parturition, and colostrum and milk samples were manually collected on lactation d 0 and 14, respectively. Results showed that averaged over three reproductive cycles, sows fed the HF diet farrowed more piglets born alive (P = 0.049) and litter weight (total born, P = 0.001; born alive, P = 0.001), increased placental weight (P < 0.001), lactation feed intake (P = 0.042), and average weaned pig BW (P = 0.014), and shortened parturition progress (P < 0.05); tended to have higher average pig BW total born (P = 0.092). Reproductive cycle had significant effects (P < 0.05) on sow BW, duration of parturition, placental weight, lactation feed intake, litter size and weight, and average pig BW. An interaction between fiber treatment and reproductive cycle was detected for placental weight. Sows fed the HF diet in parities 2 and 3 had greater placental weight than the other sows (P = 0.007). In addition, sows fed the HF diet had lower (P < 0.05) preprandial low-density lipoprotein and endotoxin concentrations, and greater (P < 0.05) plasma estrogen and lutropin concentrations on d 110 of gestation; had higher plasma oxytocin (P < 0.05) and epinephrine (P < 0.10) levels at farrowing compared with sows fed the CON diet. Colostrum and milk compositions were not influenced by the treatment. Above all, when the daily intake of the basal gestation diet was equalized for both treatments, dietary fiber supplementation to the gestation diet with an equal ISF/SF ratio over three reproductive cycles improved sow and litter performance.

Nerve Growth Factor (NGF) and Animal Reproduction.

Stimuli that lead to the release of gonadotropin-releasing hormone (GnRH) and pituitary gonadotropins and, consequently, ovulation in mammals fall into two broad categories. In the first, high plasma oestrogen concentrations induce the events that trigger ovulation, a characteristic of spontaneous ovulators. In the second, nerve stimuli occurring during mating reach the hypothalamus and trigger the release of GnRH and ovulation with a neuroendocrine reflex that characterizes induced ovulators.In this review, we will give an overview of the distribution of NGF and its expression in the different tissues of the male accessory sex glands, the main sites of NGF production. Next, we will highlight the role of NGF in sperm function and its potential cryopreserving role in artificial insemination techniques. Finally, we will evaluate the functions of NGF in ovulation, particularly in induced ovulators. Overall, the information obtained so far indicates that NGF is widely distributed in organs that regulate the reproductive activity, in both males and females. In spontaneous ovulators, NGF exerts mainly a luteotrophic action, while, in induced ovulators it is the main ovulation-inducing factor. A better understanding of the role of NGF in reproduction would be of great interest, since it could help finding innovative therapeutic aids to improve mammalian fertility.

Menstrual cycle phase does not affect whole body peak fat oxidation rate during a graded exercise test.

Female sex hormones fluctuate in a predictable manner throughout the menstrual cycle in eumenorrheic women. In studies conducted in both animal and humans, estrogen and progesterone have been found to exert individual metabolic effects during both rest and exercise, suggesting that estrogen may cause an increase in fat oxidation during exercise. However, not all studies find these metabolic changes with the natural physiological variation in the sex hormones. To date, no studies have investigated whether whole body peak fat oxidation rate (PFO) and maximal fat oxidation intensity (FATmax) are affected at different time points [mid-follicular (MF), late-follicular (LF), and mid-luteal (ML)] in the menstrual cycle, where plasma estrogen and progesterone are either at their minimum or maximum. We hypothesized that an increased plasma estrogen concentration together with low progesterone concentration in LF would result in a modest but significant increase in PFO. We found no differences in body weight, body composition, or peak oxygen uptake (V̇o2peak) between any of the menstrual phases in the 19 healthy, young eumenorrheic women included in this study. PFO [MF: 0.379 (0.324-0.433) g/min; LF: 0.375 (0.329-0.421) g/min; ML: 0.382 (0.337-0.442) g/min; mean ± (95% CI)] and resting plasma free fatty acid concentrations [MF: 392 (293-492) µmol/l; LF: 477 (324-631) µmol/l; ML: 396 (285-508) µmol/L] were also similar across the menstrual cycle phases. Contrary to our hypothesis, we conclude that the naturally occurring fluctuations in the sex hormones estrogen and progesterone do not affect the whole body PFO and FATmax in young eumenorrheic women measured during a graded exercise test.NEW & NOTEWORTHY Menstrual cycle phase does not affect the peak fat oxidation rate during a graded exercise test. Natural physiological fluctuations in estrogen do not increase peak fat oxidation rate. FATmax is not influenced by menstrual cycle phase in healthy, young eumenorrheic women.

Flavonoid Intake and Plasma Sex Steroid Hormones, Prolactin, and Sex Hormone-Binding Globulin in Premenopausal Women.

Background: Flavonoids potentially exert anti-cancer effects, as suggested by their chemical structures and supported by animal studies. In observational studies, however, the association between flavonoids and breast cancer, and potential underlying mechanisms, remain unclear. Objective: To examine the relationship between flavonoid intake and sex hormone levels using timed blood samples in follicular and luteal phases in the Nurses’ Health Study II among premenopausal women. Methods: Plasma concentrations of estrogens, androgens, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), prolactin, and sex hormone-binding globulin (SHBG) were measured in samples collected between 1996 and 1999. Average flavonoid were calculated from semiquantitative food frequency questionnaires collected in 1995 and 1999. We used generalized linear models to calculate geometric mean hormone concentrations across categories of the intake of flavonoids and the subclasses. Results: Total flavonoid intake generally was not associated with the hormones of interest. The only significant association was with DHEAS (p-trend = 0.02), which was 11.1% (95% confidence interval (CI): −18.6%, −3.0%) lower comparing the highest vs. lowest quartile of flavonoid intake. In subclass analyses, the highest (vs. lowest) quartile of flavan-3-ol intake was associated with significantly lower DHEAS concentrations (−11.3% with 95% CI: −18.3%, −3.7%, p-trend = 0.01), and anthocyanin intake was associated with a significant inverse trend for DHEA (−18.0% with 95% CI: −27.9%, −6.7%, p-trend = 0.003). Conclusion: Flavonoid intake in this population had limited impact on most plasma sex hormones in premenopausal women. Anthocyanins and flavan-3-ols were associated with lower levels of DHEA and DHEAS.

Transgender women on oral HIV pre-exposure prophylaxis have significantly lower tenofovir and emtricitabine concentrations when also taking oestrogen when compared to cisgender men.

IntroductionOral HIV Pre‐Exposure Prophylaxis (PrEP) with tenofovir (TFV) disoproxil fumarate (TDF)/emtricitabine (FTC) is highly effective. Transgender women (TGW) have increased HIV risk, but have been underrepresented in trials. For TGW on oestrogens for gender‐affirming hormone treatment (GAHT), TDF/FTC‐oestrogen interactions may negatively affect HIV prevention or gender‐affirming goals. Our aim was to evaluate any pharmacokinetic drug‐drug interaction between GAHT and TDF/FTC.MethodsWe performed a pharmacokinetic study, in an urban outpatient setting in 2016 to 2018, of the effects of GAHT on TFV, FTC and the active forms TFV diphosphate (TFV‐DP) and FTC triphosphate (FTC‐TP) in eight TGW and eight cisgender men (CGM). At screening, participants were HIV negative. TGW were to maintain their GAHT regimens and have plasma oestradiol concentrations >100 pg/mL. Under direct observation, participants took oral TDF/FTC daily for seven days. At the last dose, blood was collected pre‐dose, one, two, four, six, eight and twenty‐four hours, and colon biopsies were collected at 24 hours to measure drug concentration. TGW versus CGM concentration comparisons used non‐parametric tests. Blood and colon tissue were also obtained to assess kinase expression.ResultsPlasma TFV and FTC C24 (trough) concentrations in TGW were lower by 32% (p = 0.010) and 32% (p = 0.038) respectively, when compared to CGM. Plasma TFV and FTC 24‐hr area under the concentration‐time curve in TGW trended toward and was significantly lower by 27% (p = 0.065) and 24% (p = 0.028) respectively. Peak plasma TFV and FTC concentrations, as well as all other pharmacokinetic measures, were not statistically significant when comparing TGW to CGM. Oestradiol concentrations were not different comparing before and after TDF/FTC dosing. Plasma oestrogen concentration, renal function (estimated creatinine clearance and glomerular filtration rate), and TFV and FTC plasma concentrations (trough and area under the concentration‐time curve) were all correlated.ConclusionsGAHT modestly reduces both TFV and FTC plasma concentrations. In TGW taking GAHT, it is unknown if this reduction will impact the HIV protective efficacy of a daily PrEP regimen. However, the combination of an on demand (2 + 1 + 1) PrEP regimen and GAHT may result in concentrations too low for reliable prevention of HIV infection.

Unravelling fatty liver haemorrhagic syndrome: 1. Oestrogen and inflammation

ABSTRACT Previous studies have implicated oestrogen as a factor in the induction of fatty liver haemorrhagic syndrome (FLHS). In this study, a refined laying hen model was employed to permit further investigations. Intramuscular (i.m.) injections of exogenous oestrogen as β-estradiol-17-dipropionate (E2) (5 mg/kg BW) were given every 4 days for 20 days to 30-week-old hens fed either ad libitum or with restricted feed intake. Elevated (P < 0.01) plasma oestrogen concentrations produced significant macroscopic and microscopic hepatic alterations. Hens in the E2-treated ad libitum fed (EAL) group experienced a higher incidence of FLHS than hens in the E2-treated restricted feed intake group, showing that birds with a higher feed intake are more at risk of developing FLHS. Histological examination of livers revealed that hens in the E2-treated ad libitum fed group had consistent and severe fat infiltration in the liver, and fat vacuolization within hepatocytes. Fat accumulation and fat droplets were found not only in the cytoplasm of hepatocytes but also in liver sinusoids. White blood cell counts and fibrinogen concentrations were altered (P < 0.01) in hens treated with E2 when compared with controls. Plasma fibrinogen concentrations were altered over time, and correlated with white blood cell counts (Pearson’s correlation r = 0.96; P = 0.001). Hens treated with E2 had increased (P < 0.01) levels of cholesterol and triglycerides, confirming that E2 induced hypercholesterolaemia and hypertriglyceridaemia. It was concluded that E2 successfully induced FLHS in hens, with typical systemic and hepatic events resulting from a disturbance in lipid metabolism and chronic low-grade inflammation.

Effects of SLCO1B1 polymorphisms on plasma estrogen concentrations in women with breast cancer receiving aromatase inhibitors exemestane and letrozole.

Aim: This study tested for associations between SLCO1B1 polymorphisms and circulating estrogen levels in women with breast cancer treated with letrozole or exemestane. Patients & methods: Postmenopausal women with hormone-receptor positive breast cancer were genotyped for SLCO1B1*5 (rs4149056) and rs10841753. Pretreatment and on-treatment plasma estrogens and aromatase inhibitor (AI) concentrations were measured. Regression analyses were performed to test for pharmacogenetic associations with estrogens and drug concentrations. Results:SLCO1B1*5 was associated with elevated pretreatment estrone sulfate and an increased risk of detectable estrone concentrations after 3months of AI treatment. Conclusion: These findings suggest SLCO1B1 polymorphisms may have an effect on estrogenic response to AI treatment, and therefore may adversely impact the anticancer effectiveness of these agents.

Development of a domestic animal model for endometriosis: Surgical induction in the dog, pigs, and sheep

Background: Endometriosis affects one in ten women of reproductive age but it is diagnosed at advanced stages. Our objective was to develop a domestic animal model that would permit sequential assessment of endometriotic changes. Materials and methods: Surgical transplantation of endometrial tissue and fat (n = 4 grafts/tissue/animal) was done in dogs (n = 5), pigs (n = 4), and sheep (n = 5). Autologous grafts were sutured to the visceral (urinary bladder in dogs and pigs and uterus in sheep) and parietal peritoneum. Sham surgeries were performed (dogs and sheep n = 5 and pigs n = 3) by placing fat grafts alone. Plasma estrogen and progesterone concentration was performed prior to surgery and weekly following surgery until euthanasia. Animals were euthanized between 80 and 110 days after surgery. Gross and histopathologic features of endometriotic lesions were recorded. Results: A variety of lesions from transplanted endometrial grafts included endometriotic cysts, vesicles, solid lesions, or absence of lesions. The proportion of cysts was greater (p &lt; 0.01) in dogs (18/20 grafts) than in pigs (5/16) and sheep (5/20). The area of endometriotic lesions at the time of euthanasia was greater than at the time of surgery in dogs (0.89 ± 0.11 cm2 vs 0.50 ± 0.09 cm2; p &lt; 0.05), whereas, the size of lesions decreased (p &lt; 0.05) by half or more in pigs and sheep. In dogs, endometrial cysts were characterized by simple cuboidal/columnar epithelium, endometrial glands, stromal tissue with hemorrhage and/or hemosiderin-laden macrophages, and smooth muscle cells. Conclusion: The development of endometriotic cysts was apparent in dogs than in sheep and pigs. Therefore, dog is a better domestic animal model for endometriosis.

Association of a low-expression SLCO1B1 polymorphism with estrogen concentrations before and during aromatase inhibitor treatment for breast cancer.

543Background: Three aromatase inhibitors (AI), the steroid exemestane, and the azoles anastrozole and letrozole, are effective in the treatment of estrogen receptor positive (ER+) breast cancer by preventing biosynthesis of estrogens including estradiol (E2), estrone (E1), and estrone-sulfate (E1S) in postmenopausal women. OATP1B1, encoded by SLCO1B1, transports E1S into the liver for desulfation to active E1. Women carrying the low-expression SLCO1B1 rs4149056 single nucleotide polymorphism (SNP) have higher E1-conjugate levels (Dudenkov Breast Cancer Res Treat 2017). We hypothesized that patients carrying this SNP would have increased E1S at baseline, and this E1S reserve could resupply E1 and E2 resulting in detectable estrogen levels during AI treatment. Methods: Five hundred postmenopausal women with ER+ breast cancer were randomized 1:1 to either exemestane 25 mg/day or letrozole 2.5 mg/day. Plasma estrogen concentrations were measured prior to and after 3 months of AI treatment using LC/MS/MS (LLO...

Calcium metabolism-related hormonal changes in layers experimentally infected with Salmonella Gallinarum

The present study was conducted to investigate the calcium metabolism-related hormonal changes in layers experimentally infected with Salmonella Gallinarum. A total of 20 18-week-old ISA brown layers were purchased from a commercial poultry farm in Kujama farm, Kaduna State, Nigeria. The birds were allowed to acclimatize for a period of 4 weeks prior to commencement of the experiment. On the day of infection with Salmonella Gallinarum, the birds were randomly divided into two groups, infected and control, of 10 birds each. To establish the infection, each bird in the infected group was orally administered 0.5 ml of the inoculum containing 9 × 108 CFU/ml. Similarly, birds in the control group were each administered 0.5 ml normal saline only. Following the inoculation, all experimental birds were closely monitored for clinical signs of fowl typhoid. Blood samples were collected from each group and was dispensed into heparinized bottles for plasma separation at day zero (day 0), 2, 4, 7, 14, 21, 28, 35, and 42 post-infection (pi) and was used for determination of hormones and electrolyte parameters. By day 7 post-infection, all birds in the infected group showed clinical signs typical of fowl typhoid, namely weakness, ruffled feathers, huddling together, somnolence, greenish-yellow diarrhea, weight loss, drop in egg production, decrease in feed and water consumption, and mortality rate (50%). There were, however, significant decrease in plasma calcium and phosphorus concentrations and significant increase in plasma estrogen and parathyroid hormone concentration in the Salmonella Gallinarum-infected layers. In conclusion, the decrease in plasma calcium and phosphorus concentrations observed in the Salmonella Gallinarum experimentally infected layers was a consequence of hepatic, renal, and gastrointestinal lesions and not due to endocrine dysfunction as plasma levels of the hormones did not suggest so.

Circulating endothelial progenitor cells in pregnant women with premature rupture of membranes: potential association with placental disorders.

The frequency of preterm labour has risen over the last few years. Plasma oestrogen concentrations differ between patients who deliver before term and those who deliver at term. Oestrogen can influence the kinetics of circulating endothelial progenitor cells (cEPCs). Here, we attempted to identify the potential association of cEPCs with the incidence of complications typical of prematurity. The study groups consisted of 60 pregnant women with premature rupture of membranes (PROM; less than 37 weeks) and 50 term pregnant women (more than 38 weeks). cEPCs were isolated from term pregnant women and pregnant women with PROM and then migratory, proliferative, tubulogenic and functional properties of these cells along with serum secretion of important EPC chemotactic cytokines were analysed. In addition, the effect of 17β-oestradiol on biological features of cEPCs harvested from pregnant women was investigated. Our results showed that an increased concentration of oestrogen in women with PROM was associated with increased numbers of cEPCs, with these cells having increased oestrogen receptor α expression together with augmented proliferative, migratory and colony-formation properties. 17β-oestradiol induced proliferation, migration and angiogenic secretory activity of cEPCs from pregnant women. Overall, circulation mobilisation of EPCs in pregnant women may be associated with placental disorders.

From Pregnancy to Preeclampsia: A Key Role for Estrogens.

Preeclampsia (PE) results in placental dysfunction and is one of the primary causes of maternal and fetal mortality and morbidity. During pregnancy, estrogen is produced primarily in the placenta by conversion of androgen precursors originating from maternal and fetal adrenal glands. These processes lead to increased plasma estrogen concentrations compared with levels in nonpregnant women. Aberrant production of estrogens could play a key role in PE symptoms because they are exclusively produced by the placenta and they promote angiogenesis and vasodilation. Previous assessments of estrogen synthesis during PE yielded conflicting results, possibly because of the lack of specificity of the assays. However, with the introduction of reliable analytical protocols using liquid chromatography/mass spectrometry or gas chromatography/mass spectrometry, more recent studies suggest a marked decrease in estradiol levels in PE. The aim of this review is to summarize current knowledge of estrogen synthesis, regulation in the placenta, and biological effects during pregnancy and PE. Moreover, this review highlights the links among the occurrence of PE, estrogen biosynthesis, angiogenic factors, and cardiovascular risk factors. A close link between estrogen dysregulation and PE occurrence might validate estrogen levels as a biomarker but could also reveal a potential approach for prevention or cure of PE.

Comparison of different regimens of estradiol benzoate treatments followed by long-acting progesterone to prepare noncycling mares as embryo recipients

The present study evaluated the influence of different regimens of estradiol benzoate (EB) treatments followed by a single dose of long-acting progesterone (LA P4) on plasma estrogen and P4 concentrations in noncyclic mares prepared as embryo recipients. Twenty-one anestrous mares were distributed into three groups (n = 7 mares per group), according to the EB dose received (single dose of 2.5 mg, total of 5 mg in decreasing doses, and total of 10 mg in decreasing doses), which was followed by a single administration of 1500 mg of LA P4 in all groups. Mares were reevaluated during the ovulatory phase and seven of them became part of the cyclic nontreated control group. Ultrasonography was performed to monitor endometrial edema, and blood samples were collected to measure estradiol (E2), estrogen conjugate (EC), and P4 by RIA. Maximum uterine edema was achieved 24 hours after administration of EB in all treated groups. Maximum E2 concentrations were observed 24 hours after the first EB injection in treated groups and there were no differences (P > 0.05) among treatments. Maximum EC concentration was observed 24 hours after the single EB injection in the 2.5-mg group, whereas in the 5- and 10-mg groups EC peaks were observed 48 hours after the first EB administration. Maximum P4 concentrations were detected 24 hours after LA P4 injection, although higher P4 concentrations were observed in the group treated with 2.5 mg of EB than in that treated with 10 mg of EB (P < 0.05). Because P4 concentrations were reduced after administration of high doses of EB, we also measured 17α-hydroxyprogesterone (17-OH-P) to test the hypothesis that high concentrations of EB would accelerate the conversion of P4 to 17-OH-P. However, 17-OH-P concentrations paralleled P4 profile in all groups, irrespective of EB doses. In summary, the three EB treatment regimens induced similar E2 peaks, although the observation of EC peaks 24 hours after E2 peaks in the 5- and 10-mg groups indicate that an excess of E2 was given, which was converted into EC to be inactivated. Administration of 10 mg of EB reduced P4 concentrations 24 hours after LA P4 was given. We demonstrated that the mechanism by which this reduction occurred was not by an increase in P4 metabolism to 17α-OH-P. In conclusion, the use of 2.5 mg of EB followed by 1500 mg of LA P4 appears to be a more appropriate regimen to treat noncyclic mares, although additional studies are needed to verify embryo survival with this treatment dose.

Hemorheological effects of secoisolariciresinol in ovariectomized rats.

Postmenopausal women often develop hemorheological disorders which may affect the systemic blood circulation and present a cardiovascular risk factor. We evaluated effects of secoisolariciresinol (SECO), a phytoestrogen, on hemorheological parameters and lipid peroxidation in a model of the age-related and/or surgical menopause induced by ovariectomy in rats. Arterial blood was sampled from sham-operated female rats, ovariectomized rats (OVX), and OVX treated with SECO (OVXSECO) (20 mg/kg/day intragastrically for two weeks). Plasma estrogen concentration and the following hemorheological parameters were measured: RBC aggregation (half-time of aggregation, T1/2; amplitude of aggregation, AMP; aggregation index, AI), RBC deformability (elongation index, EI), whole blood viscosity at the shear rate of 3-300s-1, plasma viscosity, hematocrit, plasma fibrinogen. Lipid peroxidation was evaluated by measuring conjugated dienes (CD) and thiobarbituric acid reactive substances (TBARS) in plasma. Ovariectomy in rats caused a 60% decrease in plasma estrogen level and triggered the development of macro- and microhemorheological abnormalities. Blood viscosity increased by 12-31%, RBC elongation index reduced by 16-28%, and T1/2 and AI increased by 35% and 29% respectively. The increase in blood viscosity correlated predominantly with reduced RBC deformability. Plasma CD and TBARS were elevated by 47% and 104% respectively. SECO therapy for OVX rats reduced blood viscosity by 9-18% and T1/2 by 32%, and increased EI by 4-17%. SECO therapy disrupted the correlation between blood viscosity and RBC deformability. Lipid peroxidation was significantly inhibited, as shown by the reduction in CD and TBARS plasma concentrations by 89% and 70% respectively. SECO did not affect plasma viscosity, estrogen or fibrinogen levels. SECO treatment for OVX rats improves blood macro- and microrheological parameters, possibly through antioxidant protection of RBC.

Nandrolone decanoate induces cardiac and renal remodeling in female rats, without modification in physiological parameters: The role of ANP system.

Anabolic-androgenic steroids are misused, including women, but little is known about the cardiovascular effects of these drugs on females. Evaluated the effects of nandrolone decanoate (ND), physical exercise and estrogen deficiency on female rats. Female Wistar rats were divided into 8 groups: S and OVX: (SHAM: sham surgery; OVX: ovariectomy, vehicle), SE and OVXE (resistance exercise 5 times a week, vehicle), SD and OVXD (treated with ND, 20 mg/kg/week for 4 weeks); SDE and OVXDE. Treatments were initiated 21 days after surgery. The Bezold–Jarisch reflex was assessed by Phenylbiguanide administration. The right atrium, kidney, and serum were collected for molecular analyses by RT-PCR of atrial natriuretic peptide (ANP), A-type natriuretic peptide receptor (NPR-A) and NPR-C. ELISA assay to estradiol and testosterone concentrations. The gastrocnemius muscle, heart and kidney weights/tibia length were measured.Morphometric analysis of heart was made (H/E) and collagen content of heart and kidney were evaluated using Pirossirius Red. ND treatment increased ANP expression on atrium and decreased NPR-A expression in kidney. Physical exercise and ovariectomy did not alter this parameter. NPR-C level was reduced in the SDE and OVXDE. Renal and cardiac hypertrophy was observed after ND treatment, with collagen deposition. Plasma estrogen concentrations were reduced and serum testosterone concentrations were increased after ND treatment. ANP has an important role in modulating the cardiovascular effects of ND in females. Thismodulating may have occurred by the increasing ANP expression, reducing NPR-A and NPR-C expression levels, and changing sex hormone levels.

Evidence of estrone-sulfate uptake modification in young and middle-aged rat prostate

High plasma exposure to estrogens is often associated with prostate cancer. Reducing this phenomenon may present therapeutic benefits. The involvement of estrone sulphate (E1S), the most abundant circulating estrogen in men, has been partially studied in this age-related pathology. To investigate the consequences of plasma E1S overload on blood and prostate sex steroid levels and inflammatory tissue responses, young and middle-aged male rats were treated with E1S with or without steroid sulfatase (STS) inhibitor STX64 for 21 consecutive days. A plasma and prostate tissue steroid profile was determined. STS activity, mRNA expression of E1S organic anion transporting polypeptides (slco1a2, slco2b1, slco4a1) and pro-inflammatory cytokines (Il1-beta, Il6, TNF-alpha) were evaluated in prostate tissue according to age and treatment group.A significant correlation between plasma and prostate steroid levels related to hormone treatment was observed in all rat age groups. However, while the E1S level in prostate tissue increased in middle-aged treated rats (p<0.0001), no significant variation was observed in young treated rats. The protective effect of STX64 during E1S infusion was observed by the maintenance of low free estrogen concentrations in both plasma and tissue. However, this protection was not associated with mRNA expression stability of pro-inflammatory cytokines in older rat prostate.These results suggest that E1S uptake in rat prostate cells increases during aging. Therefore, if a similar phenomenon existed in men, preventively reducing the STS activity could be of interest to limit uptake of estrogens in prostate when high E1S plasma level is assayed.

Reproductive Toxicity to Male Mice of Nose Only Exposure to Water‐ Pipe Smoke

Data on the possible adverse reproductive effects of water pipe smoking (WPS) are lacking. Here, we assessed the effects of exposure to WPS in mice. The duration of the session was 30 min/day for one month. Control mice were exposed to air. Twenty- four h after the last exposure, mice were killed and the testes and plasma removed. Testicular protein, alkaline phosphatase, several indices of oxidative damage and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) were quantified. The plasma concentrations of leptin, and reproductive hormones were also measured. Histological analysis of testes and lungs was also conducted. WPS caused statistically significant decreases in the plasma concentrations of leptin, testosterone, and LH, and in the concentrations of total protein and the antioxidant indices measured. A statistically non - significant decrease in VEGFR2 protein in the WPS - exposed mice was also found. The body and testicular weights of mice exposed to WPS , as well as testicular alkaline phosphatase activity and light microscopic histology, and plasma estrogen concentration were all not significantly affected by WPS. Further studies on the functional implications of these findings in mice exposed to WPS for longer duration are warranted.

The effect of bifenthrin on the dopaminergic pathway in juvenile rainbow trout (Oncorhynchus mykiss)

Bifenthrin is a type I pyrethroid pesticide, which has been shown to increase plasma estrogen concentrations in several fish models. The mechanism of action by which bifenthrin alters 17β-estradiol (E2) is unclear. E2 biosynthesis is regulated through pituitary follicle stimulating hormone, which is directly controlled by hypothalamic gonadotropin releasing hormone (GnRH2). Since dopaminergic signaling significantly influences GnRH2 release in fish, the goal of the study was to determine the effect of a 96h and 2 weeks exposure to bifenthrin on dopaminergic signaling in juvenile rainbow trout (Oncorhynchus mykiss) (RT). Our results indicated that a decrease in dopamine receptor 2A (DR2A) expression was associated with a trend toward an increase in plasma E2 following exposure at 96h and 2 weeks, and a significant increase in the relative expression of vitellogenin mRNA at 2 weeks. DR2A mRNA expression decreased 426-fold at 96h and 269-fold at 2 weeks in the brains of 1.5ppb (3.55pM) bifenthrin treated RT. There was an increase in tyrosine hydroxylase transcript levels at 96h, which is indicative of dopamine production in the brains of the 1.5ppb (3.55pM) bifenthrin treated RT. A significant increase in the relative expression of GnRH2 was observed at 96h but a significant decrease was noted after 2 weeks exposure indicating potential feedback loop activation. These results indicate that the estrogenic-effects of bifenthrin may result in part from changes in signaling within the dopaminergic pathway, but that other feedback pathways may also be involved.