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Reproductive Toxicology

P A Stapleton, C R McBride, J Yi, A B Abukabda, T R Nurkiewicz
Preconceptive health encompasses male and female reproductive capability. In females, this takes into account each of the stages of the estrous cycle. Microvascular reactivity varies throughout the estrous cycle in response to hormonal changes and in preparation for pregnancy. Microvascular alterations in response to engineered nanomaterial (ENM) exposure have been described within 24-hours of inhalation; however, the impact upon the uterine vasculature at differing estrous stages and at late-stage pregnancy is unclear...
March 12, 2018: Reproductive Toxicology
Edward W Pietryk, Kiristin Clement, Marwa Elnagheeb, Ryan Kuster, Kayla Kilpatrick, Michael I Love, Folami Y Ideraabdullah
In utero exposure to vinclozolin (VIN), an antiandrogenic fungicide, is linked to multigenerational phenotypic and epigenetic effects. Mechanisms remain unclear. We assessed the role of antiandrogenic activity and DNA sequence context by comparing effects of VIN vs. M2 (metabolite with greater antiandrogenic activity) and wild-type C57BL/6 (B6) mice vs. mice carrying mutations at the previously reported VIN-responsive H19/Igf2 locus. First generation offspring from VIN-treated 8nrCG mutant dams exhibited increased body weight and decreased sperm ICR methylation...
March 10, 2018: Reproductive Toxicology
Jiu-Zhen Jin, Zhenmin Lei, Zi-Jian Lan, Partha Mukhopadhyay, Jixiang Ding
Numerous studies have been conducted to understand the molecular mechanisms controlling mammalian secondary palate development such as growth, reorientation and fusion. However, little is known about the signaling factors regulating palate initiation. Mouse fibroblast growth factor (FGF) receptor 2 gene (Fgfr2) is expressed on E11.5 in the palate outgrowth within the maxillary process, in a region that is responsible for palate cell specification and shelf initiation. Fgfr2 continues to express in palate on E12...
March 8, 2018: Reproductive Toxicology
SriDurgaDevi Kolla, Mary Morcos, Brian Martin, Laura N Vandenberg
Throughout life, mammary tissue is strongly influenced by hormones. Scientists have hypothesized that synthetic chemicals with hormonal activities could disrupt mammary gland development and contribute to breast diseases and dysfunction. Bisphenol S (BPS) is an estrogenic compound used in many consumer products. In this study, CD-1 mice were exposed to BPS (2 or 200 μg/kg/day) during pregnancy and lactation. Mice exposed to 0.01 or 1 μg/kg/day ethinyl estradiol (EE2), a pharmaceutical estrogen, were also evaluated...
March 8, 2018: Reproductive Toxicology
Yuxian Yang, Xiaorong Fan, Jianying Tao, Ting Xu, Yingying Zhang, Wenna Zhang, Lingjun Li, Xiang Li, Hongmei Ding, Miao Sun, Qinqin Gao, Zhice Xu
Prenatal hypoxia causes intrauterine growth retardation. It is unclear whether/how hypoxia affects the bone in fetal and offspring life. This study showed that prenatal hypoxia retarded fetal skeletal growth in rats, inhibited extracellular matrix (ECM) synthesis and down-regulated of insulin-like growth factor 1 (IGF1) signaling in fetal growth plate chondrocytes in vivo and in vitro. In addition, ovariectomized (OVX) was used for study of postmenopausal osteoporosis. Compared with the control, OVX offspring in prenatal hypoxic group showed an enhanced osteoporosis in the femurs, associated with reduced proteoglycan and IGF1 signaling...
March 7, 2018: Reproductive Toxicology
Luciana Gueiros da Motta, Juliana Alves de Morais, Ana Carolina A M Tavares, Leonora Maciel Sousa Vianna, Marcia Renata Mortari, Rivadávio Fernandes Batista Amorim, Rosângela R Carvalho, Francisco José R Paumgartten, Aline Pic-Taylor, Eloisa Dutra Caldas
Rats were treated orally with ayahuasca (AYA) on gestation days (GD) 6-20 at doses corresponding to one-(1X) to eight-fold (8X) the average dose taken by a human adult in a religious ritual, and the pregnancy outcome evaluated on GD21. Rats treated with 4X and 8X doses died during the treatment period (44 and 52%), and those that survived showed kidney injury. Rats surviving the 8X dose showed neuronal loss in hippocampal regions and in the raphe nuclei, and those from the 2X dose neuronal loss in CA1. Delayed intrauterine growth, induced embryo deaths and increased occurrence of foetal anomalies were observed at the 8X dose...
March 6, 2018: Reproductive Toxicology
Uros Midic, Benjamin Goheen, Kailey A Vincent, Catherine A VandeVoort, Keith E Latham
Trophoblast stem cells (TSCs) are crucial for embryo implantation and placentation. Environmental toxicants that compromise TSC function could impact fetal viability, pregnancy, and progeny health. Understanding the effects of low, chronic EDC exposures on TSCs and pregnancy is a priority in developmental toxicology. Differences in early implantation between primates and other mammals make a nonhuman primate model ideal. We examined effects of chronic low-level exposure to atrazine, tributyltin, bisphenol A, bis(2-ethylhexyl) phthalate, and perfluorooctanoic acid on rhesus monkey TSCs in vitro by RNA sequencing...
March 2, 2018: Reproductive Toxicology
Young-Ah You, Elsayed A Mohamed, Md Saidur Rahman, Woo-Sung Kwon, Won-Hee Song, Buom-Yong Ryu, Myung-Geol Pang
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a reproductive and developmental toxicant that can alter the sex ratio of offspring (proportion of male offspring). We hypothesized that the alteration of sex ratio is associated with sex chromosome ratio of live spermatozoa affected by exposure to TCDD. After exposure to TCDD we analyzed simultaneously sperm sex chromosome constitution and viability, and evaluated sperm sex chromosome ratio association with embryo sex ratio in mice. Short-term exposure to TCDD affects the decreased sperm motility and viability, and the increased acrosome reaction...
March 2, 2018: Reproductive Toxicology
Stephanie Padberg, Tatjana Tissen-Diabaté, Katarina Dathe, Stefanie Hultzsch, Katja Meixner, Verena Linsenmeier, Reinhard Meister, Christof Schaefer
Diclofenac is a widely used analgesic so that exposure during pregnancy may frequently occur. Most publications have evaluated the safety of NSAIDs on pregnancy outcome as a group of substances. Specific data on diclofenac are rare. This observational cohort study used the German Embryotox pharmacovigilance database to assess the risk of major birth defects and spontaneous abortion after first trimester exposure to diclofenac. A group of 260 women who took diclofenac during first trimester was compared to 778 non-exposed pregnancies...
February 22, 2018: Reproductive Toxicology
Renata Gonçalves, Ana Paula Zanatta, Fernanda Carvalho Cavalari, Monica Andressa Wessner do Nascimento, Christelle Delalande-Lecapitaine, Hélène Bouraïma-Lelong, Fátima Regina Mena Barreto Silva
We investigated the acute effect of low concentrations of BPA on calcium influx and the mechanism of action of BPA in this rapid response in the rat testis. BPA increased calcium influx at 1 pM and 1 nM at 300 s of incubation, in a similar manner to that of estradiol. At 1 pM, BPA stimulated calcium influx independently of classical estrogen receptors, consistent with a G-protein coupled receptor. This effect also involves the modulation of ionic channels, such as K+ , TRPV1 and Cl- channels. Furthermore, BPA is able to modulate calcium from intracellular storages by inhibiting SERCA and activating IP3 receptor/Ca2+ channels at the endoplasmic reticulum and activate kinase proteins, such as PKA and PKC...
February 21, 2018: Reproductive Toxicology
Melissa M Smarr, Masato Honda, Kurunthachalam Kannan, Zhen Chen, Sungduk Kim, Germaine M Buck Louis
Antimicrobials including parabens, triclosan, and triclocarban have endocrine disrupting properties. Among 501 male partners of couples planning to become pregnant, preconception urinary biomarkers of parabens, triclosan and triclocarban exposure were quantified in spot urine samples. Men also provided two fresh semen samples collected approximately one month to undergo 24-hour semen quality analysis. Linear mixed-effects models, adjusted for creatinine, race, age and body mass index, were utilized to assess the relationship between log transformed chemical concentrations rescaled by their standard deviations and semen parameters...
February 20, 2018: Reproductive Toxicology
Kadeem A Richardson, Patrick R Hannon, Yvette J Johnson-Walker, Maung Sun Myint, Jodi A Flaws, Romana A Nowak
Di-(2-ethylhexyl) phthalate (DEHP) is an endocrine-disrupting chemical that has been shown to impair normal reproductive function in males and females. This study investigated whether adult exposure to environmental and occupational doses of DEHP alters homeostasis of uterine proliferation, morphology, and number of uterine glands. Adult female CD1 mice were orally dosed with DEHP (0, 20 μg/kg/day, 200 μg/kg/day, 20 mg/kg/day or 200 mg/kg/day) for 30 days. Results indicated that DEHP at 200 μg/kg/day caused a reduction in epithelial cell proliferation in the uterus (p < ...
February 16, 2018: Reproductive Toxicology
Derik E Haggard, Pamela D Noyes, Katrina M Waters, Robert L Tanguay
There continues to be a need to develop in vivo high-throughput screening (HTS) and computational methods to screen chemicals for interaction with the estrogen, androgen, and thyroid pathways and as complements to in vitro HTS assays. This study explored the utility of an embryonic zebrafish HTS approach to identify and classify endocrine bioactivity using phenotypically-anchored transcriptome profiling. Transcriptome analysis was conducted on zebrafish embryos exposed to 25 estrogen-, androgen-, or thyroid-active chemicals at concentrations that elicited adverse malformations or mortality at 120 hours post-fertilization in 80% of animals exposed...
February 16, 2018: Reproductive Toxicology
Isiaka Abdullateef Alagbonsi, Luqman Aribidesi Olayaki
The use of Cannabis sativa (CS) has been widely demonstrated to have detrimental effect on male reproductive functions. Despite the well-known existence of endocannabinoid and melatonergic systems in semen, the physiological significance of their interaction is not understood. We recently showed that melatonin exacerbates the CS-induced gonadotoxicity in-vivo. To overcome the limitations associated with our in-vivo studies and further understand the role of cannabinoid-melatonin relationship in sperm functions, this study investigated the in-vitro effect of tetrahydrocannabinol (THC) and/or melatonin on motility and kinematics of capacitating rat sperms...
February 14, 2018: Reproductive Toxicology
Sarah M Hutchison, Louise C Mâsse, Jodi L Pawluski, Tim F Oberlander
The long-term impact of selective serotonin reuptake inhibitor (SSRI) antidepressant treatment during pregnancy and postpartum on offspring outcomes is still not clear. Specifically, perinatal SSRI exposure may have long-term consequences for body weight and related health outcomes in the newborn period and beyond. This review focuses on the impact of perinatal SSRI exposure on weight using human and animal findings. The impact of maternal mood is also explored. We propose potential mechanisms for weight changes, including how early alterations in serotonin signaling may have implications for weight via changes in metabolism and motor development...
February 12, 2018: Reproductive Toxicology
Pedro García-Fortea, Isaac Cohen-Corcia, Juan Antonio Córdoba-Doña, Alberto Reche-Rosado, Ernesto González-Mesa
We analysed the association between the concentration of four toxic elements (As, Cd, Hg and Pb) and diverse reproductive outcomes in a cohort of 194 women with fertility disorders undergoing IVF in a public hospital. Concentration in hair specimens was explored as biomarker of exposure during the three months prior to oocyte retrieval. The proportion of negative results, especially regarding pregnancy and birth outcomes, is remarkable. However, we found that the probability of mature oocytes was inversely associated with the concentration of Hg in hair (RR = 0...
February 10, 2018: Reproductive Toxicology
Ruoxin Zhang, Jinlong Zhou, Junrong Ren, Siqi Sun, Yuanyuan Di, Hanyu Wang, Xiaoqin An, Kexin Zhang, Junfeng Zhang, Zhaoqiang Qian, Meimei Shi, Yanning Qiao, Wei Ren, Yingfang Tian
Gene-environmental interaction could be the major cause of autism. The aim of the current study is to detect the effects of valproic acid on gene expression profiles and alternatively spliced genes in the prefrontal cortex in rat models of autism. Female rats received a single intraperitoneal injection of 600 mg/kg valproic acid at day 12.5 post-conception, and controls were injected with saline. Only male offspring were employed in the current study. RNA sequencing was used to investigate transcriptome in the prefrontal cortex of VPA-exposed rats...
February 7, 2018: Reproductive Toxicology
Jaqueline Vieira Carletti, Ana Correia-Branco, Claudia Raquel Silva, Nelson Andrade, Lenir Orlandi Pereira Silva, Fátima Martel
Preeclampsia is a pregnancy disorder characterized by maternal blood pressure, fetal growth restriction and intrauterine hypoxia. Folic acid is a vitamin required during pregnancy. In this work, we investigated the relationship between preeclampsia and the intake of distinct doses of folic acid during pregnancy. Considering that preeclampsia is associated with increased placental oxidative stress levels, we investigated the effect of oxidative stress induced by tert-butylhydroperoxide (TBH) in human trophoblast-derived cells cultured upon deficient/low, physiological and supra-physiological folic acid levels...
February 6, 2018: Reproductive Toxicology
Philip A May, Julie M Hasken, Marlene M De Vries, Anna-Susan Marais, Julie M Stegall, Daniel Marsden, Charles D H Parry, Soraya Seedat, Barbara Tabachnick
BACKGROUND: Alcohol use is reported accurately among pregnant women in some populations. METHODS: Self-reported alcohol use via the AUDIT and 90-day recall for 193 women from antenatal clinics was compared to biomarker results: phosphatidylethanol (PEth) from bloodspots and ethyl glucuronide (EtG) in fingernails. RESULTS: AUDIT was positive for 67.9% of respondents, and 65.3% directly reported drinking. Individual biomarkers detected less drinking (PEth = 57...
February 6, 2018: Reproductive Toxicology
Vivi F H Jensen, Anne-Marie Mølck, Jens Lykkesfeldt, Ingrid B Bøgh
Glucose is the major energy substrate during embryogenesis and the embryo is dependent on glucose from the maternal circulation to ensure normal metabolism and growth. The placenta plays a key role in this nutrient transfer in mammals, both during embryogenesis and after the development of the chorio-allantoic placental circulation. Maternal hypoglycaemia is accompanied by foetal hypoglycaemia and maternal counter-regulatory measures include a priority to nutrients in the maternal circulation by restricting their transfer to the foetus...
February 3, 2018: Reproductive Toxicology
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