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Early postnatal effects of prenatal exposure to glucocorticoids on testosterone metabolism and biogenic monoamines in discrete neuroendocrine regions of the rat brain.

We investigated the effects of hydrocortisone acetate and dexamethasone administered to pregnant rats during the last gestational week on sexual differentiation of testosterone metabolism and biogenic monoamine contents and turnover in the discrete brain regions in 10-day-old offspring. In the preoptic area, sex-dependent differences in aromatase activity were attenuated by prenatal glucocorticoids. Prenatal dexamethasone but not hydrocortisone acetate caused the inversion of sexual dimorphism of 5alpha-reductase activity in the preoptic area. In the brain preoptic area of the male pups prenatally exposed to hydrocortisone acetate, a decrease in noradrenaline turnover was found. Dopamine turnover in the preoptic area and 5-hydroxytryptamine metabolism in the preoptic area and medial basal hypothalamus increased in females as a result of hydrocortisone acetate treatment. Our results indicate that excess glucocorticoids in prenatal life modifies the basic neurochemical and neurophysiological mechanisms of sexual brain differentiation and might contribute to behavioral and reproductive disorders in adulthood.

Animals↗

Myo-inositol, glucose and zinc concentrations determined in the preconceptional period, during and after pregnancy.

OBJECTIVE: To determine the blood concentrations of myo-inositol, glucose and zinc before, during and after normal pregnancy. STUDY DESIGN: Preconceptionally, at 6, 10, 20, 30 and 37 weeks amenorrhea, and 6 weeks after delivery, blood samples of 18 nulliparae and 19 multiparae were obtained and concentrations of serum inositol and glucose, and red blood cell zinc were determined. The data were analyzed using a linear mixed model. RESULTS: The preconceptional mean (S.E.M.) inositol concentration of 21.7 (1.03) micromol/L was comparable to the concentrations at 6 and 37 weeks amenorrhea, 22.2 (1.03) micromol/L, and 19.9 (1.10) micromol/L, respectively. However, the inositol concentrations at 10 and 20 weeks amenorrhea and post partum were significantly lower than the preconceptional inositol concentration, p<0.05. The preconceptional mean (S.E.M.) glucose concentration of 3.9 (1.03) mmol/L was comparable to the concentration at 6 and 10 weeks amenorrhea, 3.9 (1.04) mmol/L and 3.8 (1.04) mmol/L respectively. Also at 20, 30 and 37 weeks amenorrhea and after delivery the glucose concentration was significantly lower than the preconceptional glucose concentration, p<0.05. Preconceptional red blood cell zinc concentrations were comparable to concentrations at 6, 10 and 20 weeks amenorrhea. At 30 and 37 weeks amenorrhea and post partum the zinc concentrations were significantly higher than in the preconceptional period (p<0.01). CONCLUSION: The concentrations of inositol, glucose and zinc significantly change during pregnancy. However, the preconceptional blood concentrations reflect the concentrations determined in the first pregnancy trimester rather well, which is important information to be used in future studies into the role of inositol, glucose and zinc in reproductive disorders.

Adult↗

Water a major source of endocrine-disrupting chemicals: An overview on the occurrence, implications on human health and bioremediation strategies.

Endocrine disrupting chemicals (EDCs) are toxic compounds that occur naturally or are the output of anthropogenic activities that negatively impact both humans and wildlife. A number of diseases are associated with these disruptors, including reproductive disorders, cardiovascular disorders, kidney disease, neurological disorders, autoimmune disorders, and cancer. Due to their integral role in pharmaceuticals and cosmetics, packaging companies, agro-industries, pesticides, and plasticizers, the scientific awareness on natural and artificial EDCs are increasing. As these xenobiotic compounds tend to bioaccumulate in body tissues and may also persist longer in the environment, the concentrations of these organic compounds may increase far from their original point of concentrations. Water remains as the major sources of how humans and animals are exposed to EDCs. However, these toxic compounds cannot be completely biodegraded nor bioremediated from the aqueous medium with conventional treatment strategies thereby requiring much more efficient strategies to combat EDC contamination. Recently, genetically engineered microorganism, genome editing, and the knowledge of protein and metabolic engineering has revolutionized the field of bioremediation thereby helping to breakdown EDCs effectively. This review shed lights on understanding the importance of aquatic mediums as a source of EDCs exposure. Furthermore, the review sheds light on the consequences of these EDCs on human health as well as highlights the importance of different remediation and bioremediation approaches. Particular attention is paid to the recent trends and perspectives in order to attain sustainable approaches to the bioremediation of EDCs. Additionally, rigorous restrictions to preclude the discharge of estrogenic chemicals into the environment should be followed in efforts to combat EDC pollution.

Animals↗

Quantitative analysis of gene regulation by seven clinically relevant progestins suggests a highly similar mechanism of action through progesterone receptors in T47D breast cancer cells.

Progesterone (P4) is an essential reproductive steroid hormone required for many aspects of female reproductive physiology. Progestins are compounds that demonstrate progesterone-like activity and are used in oral contraception, hormone therapy, and treatment of some reproductive disorders, but differ widely in their chemical structures, potency, and pharmacokinetics. While numerous studies have assessed progestins on specific endpoints, little is known about the activation of global gene expression by progestins. We used Affymetrix GeneChip U133A expression arrays to examine the action of P4 and six clinically relevant synthetic progestins (3-ketodesogestrel, drospirenone, levonorgestrel, medroxyprogesterone acetate, norethindrone acetate, and trimegestone) on the progesterone receptor (PR)-positive T47Dco and the PR-negative T47D-Y breast cancer cell lines. Excluding drospirenone, one or more of the progestins-regulated 329 genes, with 30 genes regulated by at least 2.0-fold by all progestins in the T47Dco cells. The synthetic progestins show a high degree of similarity in their transcriptional responses, and each progestin regulates between 77 and 91% of the genes regulated by P4. Independent quantitative RT-PCR analysis confirmed a similar regulation for S100P, PPL, IL20RA, NET1, ATP1A1, HIG2, and CXCL12 (SDF-1) by all seven progestins. Attempts to find differentially regulated genes by any progestin compared to all other treatments failed, suggesting any differences are quantitative, not qualitative. This analysis demonstrates a high degree of similarity among these progestins on PR-regulated gene expression in T47D cells, suggesting a similar and fairly specific mode of action.

Alkaline Phosphatase↗

Cinnamates and cinnamamides inhibit fungal 17beta-hydroxysteroid dehydrogenase.

The 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) have important roles in the regulation of steroid hormone actions through their catalysis of the oxidation or reduction of estrogens and androgens at position 17. Dysfunctions of the human 17beta-HSDs have been associated with reproduction disorders, neuronal diseases and the development of hormone-dependent forms of cancers. Therefore, these enzymes represent interesting targets for the development of new drugs. Here we present a series of new cinnamic acid esters and amides that inhibit the oxidative and reductive reaction catalyzed by 17beta-HSD from the fungus Cochliobolus lunatus, a model enzyme of the short-chain dehydrogenase/reductase superfamily. We found that esters of unsubstituted cinnamic acid were better inhibitors than esters of 3,4,5-trimethoxycinnamic acid. Cinnamates were also more potent inhibitors than structurally related cinnamamides. The compounds presented in this paper are potential leads for the development of inhibitors of human 17beta-HSD isoforms, which may prove to have different therapeutic applications.

17-Hydroxysteroid Dehydrogenases↗

Detection of bovine herpesvirus 4 in aborted bovine placentas.

Diagnostic studies on aborted placentas of cattle usually do not determine any reason for abortions. In this paper, five bovine herpesviruses (BoHVs) and some bacteriological agents were investigated by several methods in 33 aborted bovine placentas. Inclusion bodies, PCR and in situ DNA hybridization proved the presence of BoHV-4 DNA in six (18.18%) tested placentas. Positive DNA hybridization signal localized BoHV-4 DNA to placental epithelial cells macrophages and lymphocytes. By destroying epithelial cells and provoking local immune response BoHV-4 infection may inhibit physiological functions of the placenta during gestation. This finding is a further sign that BoHV-4 plays an active role in reproductive disorders of cattle.

Aborted Fetus↗

Electroacupuncture stimulates the expression of prolactin-releasing peptide (PrRP) in the medulla oblongata of ovariectomized rats.

Electroacupuncture (EA) in reproductive medicine has become established in Western medicine as a therapy over the last decade. EA performs a variety of neuromodulatory functions in the central nervous system (CNS). Prolactin-releasing peptide (PrRP) is a neuropeptide identified as an endogenous ligand for the orphan G protein-coupled receptor hGR3. PrRP can affect the function of hypothalamus-pituitary-ovary axis (HPOA) and hypothalamus-pituitary-adrenal axis (HPAA). The present study was undertaken to characterize the effect of EA on the expression of PrRP in the medulla oblongata in ovariectomized (OVX) rats by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). In addition, estrogen (E2) levels were detected by radioimmunoassay (RIA). The results suggest that EA significantly increase the blood level of E2 and the expression of PrRP in the medulla oblongata of OVX rats. The number of PrRP immunoreactive (ir) neurons was higher in the group ovariectomized with EA than that in the OVX group. The numbers of PrRP-ir neurons in intact (INT) and intact with EA (INT+EA) were not significantly different between the two groups. The expression of PrRP mRNA was increased in the OVX+EA group than that in the OVX group. These results suggest that the mechanism that EA improved reproductive disorders induced by ovariectomy in rats is related to the modulation of the blood E2 level and the expression of PrRP in the medulla oblongata.

Animals↗

Estrogenic and toxic effects of polychlorinated biphenyls on cultured ovarian germ cells of embryonic chickens.

Polychlorinated biphenyls (PCBs) are man-made ubiquitous pollutants that have detrimental effects on reproduction and endocrine functions in a variety of species. In the present study, estrogenic and toxic effects of PCBs on embryonic chicken ovarian development were evaluated by a germ-somatic cell co-culture system. Ovarian cells were cultured in serum-free medium and challenged with a mixture of PCBs (Aroclor 1254). Cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release. Results showed that lower PCBs (0.1-1 microg/ml) manifested mainly estrogenic effect to stimulate germ cell proliferation, while higher PCBs (10 microg/ml) imposed severe toxicity on germ and somatic cells. The toxic effect of PCBs could be attenuated by an antioxidant tocopherol. PCBs induced condensed nuclear chromosome in ovarian cells and caused cell exfoliation and breakdown within initial hours of treatment. After 24 h, the estrogenic effect of PCBs began to exhibit and the survived germ cells manifested proliferation. Inhibition of the estrogenic effect of PCBs by tamoxifen led to increased toxicity on germ cells and somatic cells. These results indicate that PCBs exposure may interfere with ovarian germ cell proliferation and cause reproductive disorder via both toxic and estrogenic actions in embryonic chickens.

Animals↗

In utero exposure to environmental estrogens and male reproductive health: a systematic review of biological and epidemiologic evidence.

In recent years, chemicals with hormone-like properties have become a topic of scientific and public discussion. It has been hypothesized that prenatal exposure of the male fetus to endocrine disruptors may be responsible for a series of outcomes, such as hypospadias and cryptorchidism. The purpose of this study was to review the endocrine disruption hypothesis, to present the relevant supporting evidence, to summarize the current knowledge, to identify gaps and limitations in the interpretation of published data, and to define future directions in research. An update on environmental estrogens was followed by an assessment of the biological plausibility and evidence connecting the environmental chemicalization with adverse reproductive outcomes in males. Subsequently, we carried out a systematic review of human studies attempting to document a direct effect of exogenous estrogens on the male reproductive system. The results do not support with certainty the view that environmental estrogens contribute to an increase in male reproductive disorders, neither do they provide sufficient grounds to reject such a hypothesis.

Cryptorchidism↗

Serum paraoxonase activity in dairy cows during pregnancy.

Preparturient dairy cows are at high risk of metabolic and reproductive disorders and oxidative stress is considered to be involved in these events. We investigated the serum paraoxonase activity in dairy cows during pregnancy and alterations in lipid and lipoprotein patterns in this period. The relation between paraoxonase activity and HDL-cholesterol concentration was also compared. The study was carried out on 76 pregnant lactating and 26 pregnant dry Holstein dairy cows. The serum paraoxonase activity was determined by the method of hydrolysing of paraoxon, while triglyceride, cholesterol and HDL-cholesterol concentrations were measured by the enzymatic kit methods. A significantly higher serum triglyceride concentration (P<0.001) was observed in dry cows compared to lactating cows. The total cholesterol and HDL-cholesterol concentrations were significantly lower (P<0.001) in dry cows than in lactating ones. In dry cows, paraoxonase activity was significantly lower than in those lactating (P<0.001). There was no significant difference in paraoxonase/HDL-cholesterol ratio between the investigated groups. It seems that the lower HDL concentration could be one of the causes of reduced paraoxonase activity considering the role of HDL as a carrier of most paraoxonase molecules in the blood. A decreased serum paraoxonase activity could diminish the effectiveness and total capacity of the whole antioxidative system during prepartum period in dairy cattle.

Animals↗

Toxic and hormonal effects of polychlorinated biphenyls on cultured testicular germ cells of embryonic chickens.

The toxic and hormonal effects of polychlorinated biphenyls (PCBs) on testicular germ cell development were revealed with a germ-Sertoli cell co-culture model from embryonic chickens. Testicular cells were dispersed from 18-day-old embryo and exposed to Aroclor 1254 (A1254) alone and combined with alpha-tocopherol, flutamide and tamoxifen for discretion of the toxic and hormonal actions of A1254. Cell damage was evaluated by determinations of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) leakage. Results showed that 10 microg/ml A1254 induced condensed nuclear and vacuolated cytoplasm; cell exfoliated and broke into pieces as a sign of cell degeneration after treatment for 6 h. The morphological cytotoxicity was confirmed by MTT reduction and LDH leakage assays. alpha-Tocopherol attenuated the toxic effect of A1254. After culture for 48 h, A1254 (0.1-1 microg/ml) manifested obvious hormonal effect to induce germ cell proliferation, while 10 microg/ml A1254 displayed obvious toxic and hormonal effects on germ and somatic cells. Blocking of either androgen receptor by flutamide or estrogen receptor by tamoxifen inhibited hormonal effect of A1254 on germ cell proliferation and increased the cytotoxicity. The above results indicated that A1254 exposure imposed both toxic and hormonal effects on embryonic testicular germ cell proliferation, which may cause reproductive disorder and even infertility at adulthood.

Androgen Antagonists↗

Genotyping of Ureaplasma diversum isolates using pulsed-field electrophoresis.

Ureaplasma diversum has been associated with reproductive disorders in cattle and in the present study genotypic variations among U. diversum isolates obtained from the vaginal mucus of healthy cattle and sick animals were analyzed by enzymatic digestion and pulsed-field gel electrophoresis (PFGE). The influence of time and broth volume was important in obtaining sufficient cell sediment and DNA for PFGE. The method presented a high discriminatory power and satisfactory reproducibility for the analysis of detected variations among U. diversum isolates and strains. Different band profiles and wide genotypic heterogeneity were detected but no association between DNA polymorphism and sick or healthy animals could be established.

Animals↗

Comparative genetic characterization of Porcine Circovirus type 2 samples from German wild boar populations.

PCV-2 is involved in "postweaning multisystemic wasting syndrome" (PMWS), "porcine dermatitis and nephropathy syndrome" (PDNS), respiratory and reproductive disorders, and thereby plays a crucial role in today's swine production world-wide. The virus is apparently ubiquitous in domestic pigs and has also been demonstrated in wild pigs. Up to now, a characterization of PCV-2 samples from wild pigs, which might help to estimate the possible role of wild pigs as sources of domestic pig infection, has not been carried out. Spleen samples from 16 PCV-2-positive wild pigs from hunting grounds of four regions in Germany were used for the analysis of the viral genome. In one sample, the complete sequence of the genome was determined. In the other, a 742 nucleotide fragment from the highly variable capsid sequence of the ORF2 was sequenced. Analysis of the sequences led to the identification of three PCV-2 strains. One strain, representing 14 of the 16 samples, was closely related with Chinese, but not with German strains. The genome of this strain was shortened by one nucleotide by a deletion close to the end of ORF2. The deletion led to a shift of the stop-codon and to the insertion of a further codon. Two further strains differed in up to 4.7% of nucleotides and up to 10.5% of amino acids (aa). These strains were aligned with clusters of PCV-2 samples from mainly French and German domestic origin.

Amino Acid Sequence↗

Cross-sectional survey in pig breeding farms in Hesse, Germany: seroprevalence and risk factors of infections with Toxoplasma gondii, Sarcocystis spp. and Neospora caninum in sows.

A cross-sectional survey was performed to estimate the prevalences of antibodies to Toxoplasma gondii (ELISA, IFAT), Sarcocystis spp. (ELISA, using S. miescheriana as antigen) and Neospora caninum (ELISA, immunoblotting) in sows from breeding farms in southern Hesse, Germany. A total of 2041 plasma samples of sows from 94 randomly selected farms was examined. Data on farm profiles, husbandry management and sows were collected by a questionnaire and exploratively analysed. For T. gondii the ELISA results agreed well with the results obtained by IFAT (kappa=0.71). Antibodies to T. gondii were detected by ELISA in 19% of the sows. Sixty-nine percent of the farms had at least one seropositive sow, and a within-farm seroprevalence of >or=50% was observed in 14% of all farms. The prevalence of anti-T. gondii antibodies was positively correlated with the age of sows. The within-herd seroprevalence was significantly higher in farms with reproductive disorders than in those without such problems. On the farm level, the farm type 'piglet production' (versus 'pedigree breeding' or 'farrow-to-finish') was the only risk factor associated with the presence of T. gondii-seropositive sows. Antibodies to Sarcocystis spp. were found in 29% of the sows. Seventy-two percent of the farms harboured at least one seropositive sow, and a within-farm seroprevalence of >or=50% was detected in 23% of all farms. The seroprevalence increased significantly with the age of sows. On the farm level, only the farm type 'piglet production' (versus 'pedigree breeding') and the replacement of sows by purchasing (versus raising on the own farm) were identified as risk factors for seropositivity. Antibodies to N. caninum were detected in one sow using both the screening ELISA and the confirmatory immunoblotting technique. This may indicate the first natural N. caninum infection in pigs.

Age Factors↗

Monitoring and modelling of exposure to ethanol in hairdressing salons.

Personal exposure to solvents was studied among hairdressers in 28 salons in two regions during two seasons in The Netherlands. Ethanol was used as a marker for solvent exposure. Auxiliary data, such as salon and work characteristics, meteorological conditions and information on the presence of control measures, were collected during the measurements. The average exposure to ethanol was almost a factor of 200 below the occupational exposure limit, but differences in average ethanol concentrations up to a factor of 30 were present between salons. Exposure concentrations were significantly higher on Fridays than on other days of the week. Contrary to expectation, exposures were somewhat lower in the spring than in the summer and in an urban than a semi-rural area. An empirical statistical model based on exposure data collected during the first measurement period appeared not to be valid for the encountered circumstances in the second measurement period. An alternative classification scheme based on two easily obtainable salon and task characteristics was elaborated. This scheme will be applied in an ongoing epidemiological study on reproductive disorders among hairdressers and their offspring.

Acetaldehyde↗

Clinical and subclinical colloid goitre in adult camels (Camelus dromedarius) at Kordofan region of Sudan.

Colloid goitre was diagnosed in adult camels in the Kordofan region of the Sudan. The disease is characterized by gross enlargement of the thyroid, histopathological follicular changes, reproductive disorders, low concentrations of circulating thyroid hormones (T3, T4) and normocytic normochromic anaemia. The possible cause of the condition is discussed and iodine supplementation is recommended.

Animals↗

Luteal phase deficiency after completely normal follicular and periovulatory phases.

Luteal phase defect (LPD) accounts for a significant proportion of reproductive disorders, however its etiology is still debated. A prospective study was performed on 37 ovulatory women to determine whether LPD can occur in cycles characterized by completely normal folliculogenesis. Criteria for normal folliculogenesis included: a gradual rise of serum estradiol, a luteinizing hormone (LH) surge, the presence of a dominant follicle that disappeared, an increase of serum progesterone, and normal serum levels of prolactin, testosterone, dehydroepiandrosterone sulfate, follicle-stimulating hormone, and LH. Thirty of 37 women fulfilled the above mentioned strict criteria and underwent endometrial biopsy in the late luteal phase. Seven of 30 (23%) demonstrated a delay in endometrial development and all had normal hormonal and ultrasonographic parameters of folliculogenesis and ovulation. Women with delayed endometrial development demonstrated slightly longer follicular phases (17.0 +/- 1.1 versus 14.5 +/- 0.3 days). Perfectly normal follicular and periovulatory events may be followed by deficient luteal phases.

Adult↗

Pregnancy after an unsuccessful oocyte donation cycle.

Clearly, to provide adequate counseling to women with POF, information is critically needed concerning the background incidence of spontaneous improvement in ovarian function as well as carefully designed, controlled studies to evaluate the efficacy of presumed therapeutic intervention. The case presented herein underscores our lack of adequate information about this common reproductive disorder.

Adult↗