Safety evaluation through genotoxicity and apoptotic markers following risug® induced contraception and its reversal in male rabbits
Publication date: Available online 20 July 2018Source: Reproductive ToxicologyAuthor(s): A.S. Ansari, A. Badar, N.K. LohiyaABSTRACTThe safety evaluation following vas occlusion with RISUG® and its reversal with DMSO and NaHCO3, using genotoxicity tests and apoptotic marker assays, was carried out in rabbits. Animals were divided into groups of sham operated control, vas occlusion with RISUG® for 3 & 12 months, reversal with DMSO and NaHCO3 after 3 & 12 months, respectively. Minimum incidences of micronuclei in erythrocytes and frequency of aberrant chromosomes were observed. Caspase-3 and TUNEL positive cel...
Source: Reproductive Toxicology - July 21, 2018 Category: Toxicology Source Type: research

Rosmarinic acid compromises human sperm functions by an intracellular Ca2+ concentration-related mechanism
Publication date: October 2018Source: Reproductive Toxicology, Volume 81Author(s): Meng-ge Lv, Wen-qiong Chen, Shi-qi Weng, Hou-yang Chen, Yi-min Cheng, Tao LuoAbstractRosmarinic acid (RA), a natural phenolic ester, is cytoprotective for male reproduction in animal models. The present study investigated the in vitro actions of RA on human sperm functions. Human sperm were exposed to 1, 10, 100, and 1000 μM RA in vitro and sperm functions were examined. The results showed that although RA did not affect human sperm viability, RA at 10–1000 μM dose-dependently reduced sperm motility, penetration ability, c...
Source: Reproductive Toxicology - July 20, 2018 Category: Toxicology Source Type: research

Peroxisome proliferator activated receptor gamma (PPAR-γ) ligand pioglitazone regulated gene networks in term human primary trophoblast cells
In this study, the PPAR-γ regulated gene networks were characterized in human primary trophoblast cells in vitro. The trophoblasts were isolated from full term placenta after delivery and exposed to 20 µM of the PPAR-γ agonist, pioglitazone, for 72 hrs and gene expression profiles were examined. Differential expression of selected genes was confirmed with RT-qPCR. Ingenuity pathway analysis was performed to identify PPAR-γ induced biological functions and downstream signaling pathways. In response to pioglitazone treatment, 37 genes were upregulated and 42 genes were downregulated as compared...
Source: Reproductive Toxicology - July 19, 2018 Category: Toxicology Source Type: research

The effects of lead and aluminum exposure on congenital heart disease and the mechanism of oxidative stress
This study aimed to analyze the association between fetal lead or aluminum exposure and congenital heart disease (CHD) occurrence as well as to explore the mechanism of oxidative stress in heart development.MethodsLead and aluminum concentrations were measured by ICP-MS in umbilical serum. The oxidative stress statuses were analyzed by measuring SOD, GPx and MDA with colorimetric assays.ResultsHigher concentrations of Al were seen in the CHD groups compared to the controls. The risk of CHD occurrence increased markedly in the highly elevated Al group (aOR 2.08, 95%CI 1.11-3.88). With increasing Al and Pb levels, the activi...
Source: Reproductive Toxicology - July 19, 2018 Category: Toxicology Source Type: research

Effects of different antibiotics on the uterine contraction and the expression of aquaporin 5 in term pregnant rat
Publication date: Available online 18 July 2018Source: Reproductive ToxicologyAuthor(s): Adrienn Csányi, Judit Hajagos-Tóth, Anna Kothencz, Robert Gaspar, Eszter DuczaAbstractAquaporin (AQP) water channels are small hydrophobic integral membrane proteins. AQP5 expression, which is regulated by oxytocin, showed a dramatic down-regulation at the term and preterm uterus. Since antibiotics are among the drugs to treat intrauterine infections, our aim was to study the effects of antibiotics on AQP5 and uterine contractility on 22-day pregnant rats.The change in uterine AQP5 expression was investigated by PCR and W...
Source: Reproductive Toxicology - July 19, 2018 Category: Toxicology Source Type: research

Pregnancy outcome after first-trimester exposure to metformin: a prospective cohort study
Publication date: Available online 11 July 2018Source: Reproductive ToxicologyAuthor(s): Stephan Scherneck, Natalie Schlinke, Evelin Beck, Katharina Grupe, Corinna Weber-Schoendorfer, Christof SchaeferAbstractThe aim of this study was to evaluate the risk of major birth defects and spontaneous abortion after metformin use during the first trimester of pregnancy. We conducted an observational cohort study comparing pregnancies with metformin treatment during the first trimester with non-exposed women matched for BMI and year of enrolment. Pregnancies were prospectively ascertained in the German Embryotox pharmacovigilance d...
Source: Reproductive Toxicology - July 12, 2018 Category: Toxicology Source Type: research

Review of embryo-fetal developmental toxicity studies performed for pharmaceuticals approved by FDA in 2016 and 2017
Publication date: Available online 13 April 2018Source: Reproductive ToxicologyAuthor(s): Paul BarrowAbstractDetails of embryo-fetal development (EFD) studies were compiled for all FDA drug approvals in 2016–17. Rats and rabbits were used for 63% of small molecule (SM) drugs. The cynomolgus monkey was used for 47% of biopharmaceuticals. Rodent studies using the clinical mAb or animal homologue replaced monkey studies under some circumstances. EFD studies were not required for anti-cancer drugs when the mode of action was associated with known developmental risk. One quarter of SM non-oncology drugs and all tested SM ...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

The urgency for optimization and harmonization of thyroid hormone analyses and their interpretation in developmental and reproductive toxicology studies
Discussions on these topics have already been initiated, and involve expert scientists from a number of international multisector organizations. This paper provides an overview of existing issues, current activities and recommendations for moving forward. (Source: Reproductive Toxicology)
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Best Practices for Developmental Toxicity Assessment for Classification and Labeling
Publication date: Available online 16 May 2018Source: Reproductive ToxicologyAuthor(s): George Daston, Aldert Piersma, Leonello Attias, Manon Beekhuijzen, Connie Chen, Jennifer Foreman, Nina Hallmark, Isabelle LeconteAbstractMany chemicals are going through a hazard-based classification and labeling process in Europe. Because of the significant public health implications, the best science must be applied in assessing developmental toxicity data. The European Teratology Society and Health and Environmental Sciences Institute co-organized a workshop to consider best practices, including data quality and consistency, interpre...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Folic acid and primary prevention of neural tube defects: A review
Publication date: Available online 16 May 2018Source: Reproductive ToxicologyAuthor(s): Jan D. van Gool, Herbert Hirche, Hildegard Lax, Luc De SchaepdrijverAbstractWith 4 mg folic acid daily, it may take 20 weeks to reach red-blood-cell folate levels between 1050 and 1340 nmol/L, optimal for reduction of the neural tube defect risk. Therefore, folic acid supplementation should be started 5–6 months before conception. The residual risk with optimal red-blood-cell folate levels is reportedly 4.5 per 10,000 total births. The residual risk in pooled data from countries with mandatory folic acid fortification is 7.5 per...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

In-utero exposure to metformin for type 2 diabetes or polycystic ovary syndrome: A prospective comparative observational study
ConclusionMetformin-T1-exposure per se is not associated with an increased risk of major anomalies. (Source: Reproductive Toxicology)
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Is post exposure prevention of teratogenic damage possible: Studies on diabetes, valproic acid, alcohol and anti folates in pregnancy: Animal studies with reflection to human
Publication date: Available online 31 May 2018Source: Reproductive ToxicologyAuthor(s): Asher Ornoy, Gideon Koren, Joseph YanaiAbstractWe discuss the possibilities to prevent the post-exposure teratogenic effects of several teratogens: valproic acid (VPA), diabetes and alcohol. Co-administration of folic acid with VPA reduced the rate of Neural Tube Defects (NTD) and other anomalies in rodents, but apparently not in pregnant women. Antioxidants or the methyl donor S-adenosyl methionine prevented Autism Spectrum Disorder (ASD) like behavior in mice and rats. In vivo and in vitro studies demonstrated that antioxidants, arach...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Cigarette smoking impairs clinical outcomes of assisted reproductive technologies: A meta-analysis of the literature
Publication date: Available online 12 June 2018Source: Reproductive ToxicologyAuthor(s): Maria Cristina Budani, Stefania Fensore, Marco Di Marzio, Gian Mario TiboniAbstractThere is convincing evidence that cigarette smoking can impair female reproductive potential. This meta-analysis updates the knowledge regarding the effects of cigarette smoking on clinical outcomes of assisted reproductive technologies (ART). Twenty-six studies were included in this meta-analysis. Results were expressed as odds ratios (OR) with 95% confidence intervals (CI) and statistical heterogeneity between the studies was evaluated with Higgins (I2...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Ethical approval for multicenter cohort studies on drug exposure during pregnancy: A survey among members of the European Network of Teratology Information Services (ENTIS)
Publication date: Available online 18 June 2018Source: Reproductive ToxicologyAuthor(s): Ursula Winterfeld, Corinna Weber-Schöndorfer, Christof Schaefer, Erik von Elm, Thierry BuclinAbstractThe European Network of Teratology Information Services (ENTIS) is in a privileged position to perform independent post-marketing surveillance of drugs in pregnancy. The aim of this survey was to describe the legal requirements and procedures involved in obtaining ethical approval for collaborative cohort studies. We sent a survey questionnaire to all 28 Teratology Information Services (TIS), of which 25 (89%) in 18 countries compl...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Low dose exposure to HBCD, CB-153 or TCDD induces histopathological and hormonal effects and changes in brain protein and gene expression in juvenile female BALB/c mice
Publication date: Available online 20 June 2018Source: Reproductive ToxicologyAuthor(s): J.D. Rasinger, T.S. Carroll, F. Maranghi, R. Tassinari, G. Moracci, I. Altieri, A. Mantovani, A.-K. Lundebye, C. HogstrandAbstractDevelopmental health risks of chronical exposure to low doses of foodborne persistent organic pollutants (POP) are recognized but still largely uncharacterized. Juvenile female BALB/c mice exposed to either HBCD, CB-153 or TCDD at doses relevant to human dietary exposures (49.5 μg, 1.35 μg and 0.90 pg kg−1 bw−1 day−1, respectively) for 28 days displayed histopathological changes...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Protective effect of resveratrol on urogenital sinus and prostate development in rats exposed in utero to TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin)
This study evaluated the protective effects of resveratrol on the prostate development of rats exposed to TCDD. Pregnant rats received TCDD (1 μg/kg) at GD15 and/or RES (20 mg/kg/day) from GD10 to PND21. Newborn and adult males from Control, TCDD, TCDD + RES and RES groups were euthanized and the prostate was excised. On PND1, there was a reduction in the number of prostatic buds, AR-positive mesenchymal cells and proliferation index in epithelial and mesenchymal cells in TCDD group, but restored by RES. AhR immunoreactivity was greater in TCDD group than the other groups. On PND90, there was higher frequency of...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Chronic cannabidiol exposure promotes functional impairment in sexual behavior and fertility of male mice
Publication date: Available online 21 June 2018Source: Reproductive ToxicologyAuthor(s): Renata K. Carvalho, Maingredy R. Souza, Monaliza L. Santos, Francisco S. Guimarães, Roger Luís H. Pobbe, Monica L. Andersen, Renata Mazaro-CostaAbstractCannabidiol (CBD) is a potent substance extracted from Cannabis sativa. As it has been suggested that marijuana can affect the reproductive system, we decided to assess the effects of chronic CBD exposure on the male reproductive system in an animal model. 21-day old male Swiss mice received CBD for 34 consecutive days at doses (p.o.) of either 15 or 30 mg/kg, and a cont...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

A shortened study design for embryo-fetal development studies in the minipig
Publication date: Available online 22 June 2018Source: Reproductive ToxicologyAuthor(s): Céline Pique, Edward Marsden, Paul Quesada, Audrey Blondel, Lars Friis MikkelsenAbstractThe minipig is accepted from scientific and regulatory perspectives for the safety evaluation of drug candidates on embryo-fetal development. The relative size and the duration of gestation (112–115 days) in the minipig is, however, considered a drawback compared with routine smaller species. We evaluated if study duration and cost could be optimized without impacting scientific validity by performing all terminal procedures around mid-...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Depletion of follicles accelerated by combined exposure to phthalates and 4-vinylcyclohexene diepoxide, leading to premature ovarian failure in rats
Publication date: Available online 30 June 2018Source: Reproductive ToxicologyAuthor(s): Dinh Nam Tran, Eui-Man Jung, Yeong-Min Yoo, Changhwan Ahn, Hee Young Kang, Kyung-Chul Choi, Sang-Hwan Hyun, Vu Hoang Dang, Thi Ngoc Pham, Eui-Bae JeungAbstractHumans are at daily risk by simultaneous exposures to a broad spectrum of man-made chemicals in the commercial products. Several classes of chemicals have been shown to alter follicle development and reduce fertility, leading to premature ovarian failure (POF) in mammals. We investigate the synergistic effects of 4-vinylcyclohexene diepoxide (VCD) and phthalate, including di(2-et...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Editorial board members
Publication date: August 2018Source: Reproductive Toxicology, Volume 79Author(s): (Source: Reproductive Toxicology)
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Contents
Publication date: August 2018Source: Reproductive Toxicology, Volume 79Author(s): (Source: Reproductive Toxicology)
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Young mothers and higher incidence of maternal meiosis-I non- disjunction: Interplay of environmental exposure and genetic alterations during halt phase in trisomy 21
This study was conducted using a detailed questionnaire to include: paternal, maternal, clinical and family history for various confounding factors such as age and regional environmental exposures where the parents resided. Out of 120 samples 95% (N = 114) were of maternal origin, including 92% (N = 105) of meiosis 1 errors and 8% (N = 9) meiosis 2 errors. Paternal origin accounted for 5% (N = 6) and were all due to meiosis-I errors. The higher incidence of maternal meiosis-I observed in the present study suggests that human trisomy 21 non-disjunction is a result of multiple factors contributing to the orig...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

OGG1 Ser326Cys polymorphism, HIV, obesity and air pollution exposure influences adverse birth outcome susceptibility, within South African Women
This study investigated the associations of OGG1 Ser326Cys SNP in relation to HIV and obesity on the susceptibility of low-birthweight (LBW) and pre-term birth (PTB) in SA women exposed to ambient air-pollution living in Durban. In our study population, the OGG1 SNP was associated with HIV and obesity. Wild-type (CC)-carrying patients had increased susceptibility for HIV-associated LBW and PTB. Co-morbid HIV and obese patients delivered neonates with decreased birthweights. Living within the heavily-polluted south-Durban and carrying the CC-genotype increased the risk for PTB within our study population. (Source: Reproductive Toxicology)
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Cardiopulmonary consequences of gestational toxicant exposure: Symposium overview at the 56th annual SOT meeting, Baltimore, MD
Publication date: August 2018Source: Reproductive Toxicology, Volume 79Author(s): Phoebe A. Stapleton, Christopher J. Wingard, Timothy R. Nurkiewicz, Alison C. Holloway, Judith T. Zelikoff, Thomas B. Knudsen, Lynette K. RogersAbstractXenobiotic exposures affect the maternal and/or in utero environment resulting in impairments in fetal development. During the period of rapid fetal growth, developing cardiovascular systems are especially vulnerable to their environment. Furthermore, fetal exposures can evoke changes in epigenetic signatures that result in permanent modifications in gene expression. This symposium focused on ...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

The association between prenatal bisphenol A exposure and birth weight: a meta-analysis
Publication date: August 2018Source: Reproductive Toxicology, Volume 79Author(s): Cheng-Yang Hu, Feng-Li Li, Xiao-Guo Hua, Wen Jiang, Chen Mao, Xiu-Jun ZhangAbstractThe association between prenatal BPA exposure and birth weight is controversial. Here, a meta-analysis was performed to estimate the association between prenatal BPA exposure and birth weight. We searched literature addressing the association of interest in relevant databases. Data were independently extracted and analyzed using partial regression coefficient (β) and/or odds ratio (OR) and their 95% confidence intervals (CIs). We identified 140 references ...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

No evidence of adverse pregnancy outcome after exposure to ibuprofen in the first trimester – Evaluation of the national Embryotox cohort
In this study, 1117 women exposed to ibuprofen in the 1st trimester were compared to 2229 non-exposed women. Data were retrieved from the German Embryotox database. No significantly increased risk of major birth defects (4.8% vs. 4.1%; OR adjusted 1.11, 95% CI 0.75–1.64) or a distinct pattern of birth defects were found. The cumulative incidences of spontaneous abortions were similar across cohorts (15.5% vs. 16.6%; HR adjusted 0.85; 95% CI, 0.65–1.11). Subgroup analyses of pregnancies exposed for ≥7 (n = 223) and ≥30 days (n = 72) did not reveal a higher risk with increasing treatment duration....
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Perinatal BPA exposure and reproductive axis function in CD-1 mice
This study examined effects of early BPA exposure on activation of gonadotropin releasing hormone (GnRH) neurons in conjunction with a steroid-induced luteinizing hormone (LH) surge, characterized patterns of estrous cyclicity and fertility over time, and assessed the ovarian follicular reserve to further explore factors responsible for the reduced fertility we previously described in this model. The percent activated GnRH neurons was reduced in BPA-exposed females at 3–6 months, and periods of persistent proestrus were increased. These data suggest that perinatal exposure to BPA reduces GnRH neuronal activation requ...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Influencing factors, underlying mechanism and interactions affecting hypercholesterolemia in adult offspring with caffeine exposure during pregnancy
This study confirmed the influencing factors (such as a HFD and female gender) of hypercholesterolemia in IUGR offspring providing theoretical and experimental bases for the effective prevention of fetal-originated hypercholesterolemia. (Source: Reproductive Toxicology)
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Interactions of protease inhibitors atazanavir and ritonavir with ABCB1, ABCG2, and ABCC2 transporters: Effect on transplacental disposition in rats
In conclusion, we suggest that placental ABCB1 might reduce ATV maternal-to-fetal transfer and therefore represent a site for pharmacokinetic drug-drug interactions of ATV. Further studies in human placenta models are necessary to provide additional data closer to clinical environment.Graphical abstract (Source: Reproductive Toxicology)
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Perception of pregnant Japanese women regarding the teratogenic risk of medication exposure during pregnancy and the effect of counseling through the Japan drug information institute in pregnancy
ConclusionsPregnant women tend to overestimate the fetal risks of medication exposure during pregnancy. Counseling would prevent unnecessary termination. (Source: Reproductive Toxicology)
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

The anterior pituitary gap junctions: potential targets for toxicants
Publication date: August 2018Source: Reproductive Toxicology, Volume 79Author(s): María Leiza Vitale, R.-Marc PelletierAbstractThe anterior pituitary regulates endocrine organs and physiological activities in the body. Environmental pollutants and drugs deleterious to the endocrine system may affect anterior pituitary activity through direct action on anterior pituitary cells. Within the gland, endocrine and folliculostellate cells are organized into and function as individual tridimensional networks, each network regulating its activity by coordinating the connected cells’ responses to physiological or pathol...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Pregnancy outcomes after maternal betahistine exposure: A case series
ConclusionsDespite a number of limitations, this case series may be of value regarding counseling pregnant women with inadvertent betahistine exposure. Further epidemiological studies with larger sample sizes and control groups are necessary to draw more definite conclusions. (Source: Reproductive Toxicology)
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Hyperemesis gravidarum—Is it a cause of abnormal fetal brain development?
Publication date: August 2018Source: Reproductive Toxicology, Volume 79Author(s): Gideon Koren, Asher Ornoy, Matitiahu BerkovitchAbstractHyperemesis gravidarum (HG) is characterized by severe gestational nausea and vomiting, leading to dehydration, electrolyte imbalance and nutritional deficits. HG adversely affects the health and wellbeing of the woman. However, the detrimental impact of HG on fetal brain development has not been addressed.We evaluate herein the emerging evidence suggesting that HG interferes with human brain development, and discuss putative mechanisms. Evidence emerges from prospective developmental stu...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Farletuzumab, a monoclonal antibody directed against folate receptor alpha, shows no evidence of teratogenicity in cynomolgus monkeys
Publication date: August 2018Source: Reproductive Toxicology, Volume 79Author(s): Tomoyuki Moriyama, Dai Kakiuchi, Luigi Grasso, David L. Hutto, Danielle Fernando, Charles SchweizerAbstractFarletuzumab is a humanized monoclonal antibody targeting human folate receptor alpha, which is being developed as an anti-cancer drug. A non-human primate reproductive study was conducted to evaluate whether it could cause any embryonic or fetal abnormalities. Farletuzumab was administered intravenously to pregnant cynomolgus monkeys (n = 16/group) at doses of 0 or 67.5 mg/kg once weekly during gestation day (GD) 20 through 97. C-...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Effects of bisphenol A and its analogs on reproductive health: A mini review
Publication date: August 2018Source: Reproductive Toxicology, Volume 79Author(s): Jacob Steven Siracusa, Lei Yin, Emily Measel, Shenuxan Liang, Xiaozhong YuAbstractKnown endocrine disruptor bisphenol A (BPA) has been shown to be a reproductive toxicant in animal models. Its structural analogs: bisphenol S (BPS), bisphenol F (BPF), bisphenol AF (BPAF), and tetrabromobisphenol A (TBBPA) are increasingly being used in consumer products. However, these analogs may exert similar adverse effects on the reproductive system, and their toxicological data are still limited. This mini-review examined studies on both BPA and BPA analo...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Effects of histone methyltransferase inhibitor chaetocin on histone H3K9 methylation of cultured ovine somatic cells and development of preimplantation cloned embryos
The objective of this study was to assess the effects of chaetocin, an inhibitor of H3K9 methyltransferase SUV39 H, in regulating the H3K9 methylation in ovine SCNT embryos. Treatment of sheep fetal fibroblast cells with chaetocin specifically decreased the levels of H3K9 di-and trimethylation, and down-regulated the expression of H3K9 methyltransferases, SUV39H1/2 and G9A. Cloned embryos from chaetocin-treated cells could develop to the blastocyst stage at a similar rate to those derived from non-treated cells. However, direct treatment of SCNT or in vitro fertilized embryos with chaetocin impaired the embryonic developme...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Bisphenol A modulates inflammation and proliferation pathway in human endometrial stromal cells by inducing oxidative stress
Publication date: October 2018Source: Reproductive Toxicology, Volume 81Author(s): Yeon Jean Cho, Seung Bin Park, Jung Woo Park, So Ra Oh, Myoungseok HanAbstractBisphenol A (BPA) has been implicated in altered human reproductive function. The oxidative stress or change of inflammatory signaling may appear a key factor in the biological changes of the human endometrium. Using MTT assay we assessed BPA mediated modulation of oxidative stress and inflammation responses in human endometrial stromal cells (ESCs). According to the results, reactive oxygen species (ROS) generation was highest upon exposure to 1000 pmol BPA. Inc...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

The effects of flutamide on cell-cell junctions in the testis, epididymis, and prostate
Publication date: October 2018Source: Reproductive Toxicology, Volume 81Author(s): Anna Hejmej, Barbara BilinskaAbstractIn this review, we summarize recent findings on the effect of the anti-androgen flutamide on cell-cell junctions in the male reproductive system. We outline developmental aspects of flutamide action on the testis, epididymis, and prostate, and describe changes in junction protein expression and organization of junctional complexes in the adult boar following prenatal and postnatal exposure. We also discuss findings on the mechanisms by which flutamide induces alterations in cell-cell junctions in reproduc...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Vitamin E and vitamin C attenuate Di-(2-ethylhexyl) phthalate-induced blood-testis barrier disruption by p38 MAPK in immature SD rats
Publication date: October 2018Source: Reproductive Toxicology, Volume 81Author(s): Lianju Shen, Xiangliang Tang, Yi Wei, Chunlan Long, Bin Tan, Shengde Wu, Mang Sun, Yue Zhou, Xining Cao, Guanghui WeiAbstractAs an environmental endocrine disruptor, Di-(2-ethylhexyl) phthalate (DEHP) affects blood-testis barrier (BTB)-associated proteins expression, which compromises BTB integrity and causes infertility. Notably, DEHP-induced testicular toxicity is related to oxidative stress, but the specific mechanism remains unclear. Therefore, we sought to investigate this mechanism and determine whether vitamin C and vitamin E administ...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Hydroxyurea embryotoxicity is enhanced in P53-deficient mice
Publication date: October 2018Source: Reproductive Toxicology, Volume 81Author(s): Nazem El Husseini, Barbara F. HalesAbstractHydroxyurea, a ribonucleotide reductase inhibitor, is a potent teratogen in mice, causing severe limb and skeletal defects. The exposure of gestation day nine murine embryos to hydroxyurea elicits an early embryonic stress response that involves activation of the P53 transcription factor. The impact of this P53 activation on the embryotoxicity of hydroxyurea- is not known. The goal of this study was to test the hypothesis that P53 acts to suppress hydroxyurea embryotoxicity. Trp53+/− timed pre...
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Avobenzone suppresses proliferative activity of human trophoblast cells and induces apoptosis mediated by mitochondrial disruption
This study suggests that avobenzone induces mitochondrial dysfunction-mediated apoptosis leading to abnormal placentation during early pregnancy. (Source: Reproductive Toxicology)
Source: Reproductive Toxicology - July 11, 2018 Category: Toxicology Source Type: research

Review of embryo-fetal developmental toxicity studies performed for pharmaceuticals approved by FDA in 2016 and 2017
Publication date: Available online 13 April 2018Source: Reproductive ToxicologyAuthor(s): Paul BarrowAbstractDetails of embryo-fetal development (EFD) studies were compiled for all FDA drug approvals in 2016–17. Rats and rabbits were used for 63% of small molecule (SM) drugs. The cynomolgus monkey was used for 47% of biopharmaceuticals. Rodent studies using the clinical mAb or animal homologue replaced monkey studies under some circumstances. EFD studies were not required for anti-cancer drugs when the mode of action was associated with known developmental risk. One quarter of SM non-oncology drugs and all tested SM ...
Source: Reproductive Toxicology - July 5, 2018 Category: Toxicology Source Type: research

The urgency for optimization and harmonization of thyroid hormone analyses and their interpretation in developmental and reproductive toxicology studies
Discussions on these topics have already been initiated, and involve expert scientists from a number of international multisector organizations. This paper provides an overview of existing issues, current activities and recommendations for moving forward. (Source: Reproductive Toxicology)
Source: Reproductive Toxicology - July 5, 2018 Category: Toxicology Source Type: research

Best Practices for Developmental Toxicity Assessment for Classification and Labeling
Publication date: Available online 16 May 2018Source: Reproductive ToxicologyAuthor(s): George Daston, Aldert Piersma, Leonello Attias, Manon Beekhuijzen, Connie Chen, Jennifer Foreman, Nina Hallmark, Isabelle LeconteAbstractMany chemicals are going through a hazard-based classification and labeling process in Europe. Because of the significant public health implications, the best science must be applied in assessing developmental toxicity data. The European Teratology Society and Health and Environmental Sciences Institute co-organized a workshop to consider best practices, including data quality and consistency, interpre...
Source: Reproductive Toxicology - July 5, 2018 Category: Toxicology Source Type: research

Folic acid and primary prevention of neural tube defects: A review
Publication date: Available online 16 May 2018Source: Reproductive ToxicologyAuthor(s): Jan D. van Gool, Herbert Hirche, Hildegard Lax, Luc De SchaepdrijverAbstractWith 4 mg folic acid daily, it may take 20 weeks to reach red-blood-cell folate levels between 1050 and 1340 nmol/L, optimal for reduction of the neural tube defect risk. Therefore, folic acid supplementation should be started 5–6 months before conception. The residual risk with optimal red-blood-cell folate levels is reportedly 4.5 per 10,000 total births. The residual risk in pooled data from countries with mandatory folic acid fortification is 7.5 per...
Source: Reproductive Toxicology - July 5, 2018 Category: Toxicology Source Type: research

In-utero exposure to metformin for type 2 diabetes or polycystic ovary syndrome: A prospective comparative observational study
ConclusionMetformin-T1-exposure per se is not associated with an increased risk of major anomalies. (Source: Reproductive Toxicology)
Source: Reproductive Toxicology - July 5, 2018 Category: Toxicology Source Type: research

Is post exposure prevention of teratogenic damage possible: Studies on diabetes, valproic acid, alcohol and anti folates in pregnancy: Animal studies with reflection to human
Publication date: Available online 31 May 2018Source: Reproductive ToxicologyAuthor(s): Asher Ornoy, Gideon Koren, Joseph YanaiAbstractWe discuss the possibilities to prevent the post-exposure teratogenic effects of several teratogens: valproic acid (VPA), diabetes and alcohol. Co-administration of folic acid with VPA reduced the rate of Neural Tube Defects (NTD) and other anomalies in rodents, but apparently not in pregnant women. Antioxidants or the methyl donor S-adenosyl methionine prevented Autism Spectrum Disorder (ASD) like behavior in mice and rats. In vivo and in vitro studies demonstrated that antioxidants, arach...
Source: Reproductive Toxicology - July 5, 2018 Category: Toxicology Source Type: research

Cigarette smoking impairs clinical outcomes of assisted reproductive technologies: A meta-analysis of the literature
Publication date: Available online 12 June 2018Source: Reproductive ToxicologyAuthor(s): Maria Cristina Budani, Stefania Fensore, Marco Di Marzio, Gian Mario TiboniAbstractThere is convincing evidence that cigarette smoking can impair female reproductive potential. This meta-analysis updates the knowledge regarding the effects of cigarette smoking on clinical outcomes of assisted reproductive technologies (ART). Twenty-six studies were included in this meta-analysis. Results were expressed as odds ratios (OR) with 95% confidence intervals (CI) and statistical heterogeneity between the studies was evaluated with Higgins (I2...
Source: Reproductive Toxicology - July 5, 2018 Category: Toxicology Source Type: research

Ethical approval for multicenter cohort studies on drug exposure during pregnancy: A survey among members of the European Network of Teratology Information Services (ENTIS)
Publication date: Available online 18 June 2018Source: Reproductive ToxicologyAuthor(s): Ursula Winterfeld, Corinna Weber-Schöndorfer, Christof Schaefer, Erik von Elm, Thierry BuclinAbstractThe European Network of Teratology Information Services (ENTIS) is in a privileged position to perform independent post-marketing surveillance of drugs in pregnancy. The aim of this survey was to describe the legal requirements and procedures involved in obtaining ethical approval for collaborative cohort studies. We sent a survey questionnaire to all 28 Teratology Information Services (TIS), of which 25 (89%) in 18 countries compl...
Source: Reproductive Toxicology - July 5, 2018 Category: Toxicology Source Type: research

Low dose exposure to HBCD, CB-153 or TCDD induces histopathological and hormonal effects and changes in brain protein and gene expression in juvenile female BALB/c mice
Publication date: Available online 20 June 2018Source: Reproductive ToxicologyAuthor(s): J.D. Rasinger, T.S. Carroll, F. Maranghi, R. Tassinari, G. Moracci, I. Altieri, A. Mantovani, A.-K. Lundebye, C. HogstrandAbstractDevelopmental health risks of chronical exposure to low doses of foodborne persistent organic pollutants (POP) are recognized but still largely uncharacterized. Juvenile female BALB/c mice exposed to either HBCD, CB-153 or TCDD at doses relevant to human dietary exposures (49.5 μg, 1.35 μg and 0.90 pg kg-1 bw-1 day-1, respectively) for 28 days displayed histopathological changes in liver (HBCD, C...
Source: Reproductive Toxicology - July 5, 2018 Category: Toxicology Source Type: research