Epidemiological investigations have found that maternal alcohol intake increases the risk of mental illness in offspring. Our study investigated changes of depression- and anxiety-like behaviors in adult offspring caused by prenatal ethanol exposure (PEE) and explored the potential mechanism. After Wistar rats were intragastrically administered ethanol at a dose of 4 g/kg·d on the 9-20th days of pregnancy

Malathion is an organophosphate insecticide used in agriculture and for controlling vector-borne diseases such as Zika. Humans can be exposed to malathion by means of ingestion of contaminated food. The juvenile and peripubertal periods are a large window of vulnerability to the action of toxic agents. The aim of the present study was to evaluate the effects of low doses of malathion during the development

Unruptured ectopic pregnancy (UEP) is a common cause of morbidity and, occasionally, of mortality in women of reproductive age. Pharmacological intervention is a common therapeutic approach for early-stage UEP. Herein, we investigated the cytotoxic effect and novel mechanism of shikonin, a natural naphthoquinone pigment purified from Lithospermum erythrorhizon, in human trophoblast cells. These data

Obesity has been reported to induce oxidative stress, inflammation and apoptosis in the testis. The objective of this study was to determine the effects of the anti-obesity drug orlistat, on testicular oxidative stress, inflammation and apoptosis in high-fat diet (HFD)-fed rats. Twenty-four adult male Sprague Dawley rats weighing 250−300 g were randomized into four groups (n = 6/group), namely; normal

Cyclophosphamide (Cy), a chemotherapeutic agent, is widely used to treat tumoursand is also associated with premature ovarian insufficiency. 4-Hydroperoxycyclophosphamide (4-HC), an active metabolite of Cy, was used for in vitro experiments. Granulosa cells (GCs) are crucial for maintaining follicle development and are also used in reproductive toxicity research in vitro. Resveratrol (Res), a polyphenolic

Valproic acid (VPA), an antiepileptic and mood-stabilizing drug, is prescribed to women of reproductive age. VPA is associated with a 1-2% increase in neural tube defects in offspring following gestational exposure and results in epigenetic modifications induced by perturbations in transcription cofactors. Cbp and p300, two transcription cofactors, play key roles in embryonic neural development. p300

Global infertility prevalence has been increasing in recent decades, mainly due to advanced reproductive age. Concerned women look for dietary supplements with antioxidant properties advertised as a natural way to increase fertility. Curcumin (CUR) is a polyphenol with antioxidant and anti-inflammatory properties. CUR elicits apoptotic cell death as evidenced in some tumor cells. In this work, the

In utero exposure to arsenite (iAs) is known to increase disease risks later in life. We investigated the effect of in utero exposure to iAs in the drinking water on metabolic and reproductive parameters in male mouse offspring at postnatal and adult stages. Pregnant CD-1 mice were exposed to iAs (as sodium arsenite) in the drinking water at 0 (control), 10 ppb (EPA standard for drinking water), and

This study investigated the effect of naringin (NRG) on extracellular metabolism of ATP through the NOS/cGMP/PKG signaling pathway induced by Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) on exposure to Bisphenol-A (BPA) in penis. Fifty-six adult male albino rats were randomly distributed into eight (n = 7) groups. Group I: control animals, Group II was treated with 40 mg/kg L-NAME, Group

Pregnant women are an especially vulnerable population, given the sensitivity of a developing fetus to chemical exposures. However, prescribing behavior for the gravid patient is guided on limited human data and conflicting cases of adverse outcomes due to the exclusion of pregnant populations from randomized, controlled trials. These factors increase risk for adverse drug outcomes and reduce quality

Maternal diabetes induces fetal programming of cardiovascular diseases. Diabetes induced-cardiac fibrosis is a process that may start in utero and may be related to the prooxidant/proinflammatory environment. The aim of this study was to investigate the effect of a maternal diet enriched in olive oil on the levels of components and regulators of the extracellular matrix, on prooxidant markers and on

The flame retardant and plasticizer, tetrabromobisphenol-A (TBBPA) has rapidly become a common component in the manufacture of circuit boards and plastics worldwide. It is also an analog of bisphenol A (BPA), an endocrine disrupting chemical identified by the Endocrine Society. As such, TBBPA needs to be investigated for similar potential human health risks. Using rats as a model, we exposed pregnant

The incidence of spontaneous pregnancy/infant losses is highly variable in long-tailed macaques (cynomolgus monkey), making it potentially difficult to ascertain test item-related effects in developmental toxicity studies. Therefore, pregnancy normograms had been developed by Jarvis et al. [1] to aid in the distinction of normal (e.g. test facility background) versus non-normal pregnancy outcomes.

The use of valproic acid (VPA), an antiepileptic drug, during pregnancy, is known to increase various fetal risks. Since VPA has been known to inhibit histone deacetylases (HDACs); its administration could alter gene transcription levels. However, in vivo effects of VPA administration on placental transporters have not been fully elucidated. The purpose of the present study was to comprehensively evaluate

The volume of ubiquitous chemicals with estrogenic properties is on the rise and some reports relate the increase in hormonal diseases to these compounds. A morphological and immunohistochemical analysis has been performed on 42 bilateral orchiectomy specimens from adult individuals who underwent gender reassignment surgery after receiving crossed-sex hormone therapy to give insight into vascular,

Using JEG-3 and BeWo cells, we examined the effect of "real life" mixtures of polycyclic aromatic hydrocarbons (PAHs), at doses reported in maternal blood (Mix I) and in placental tissue (Mix II), on human chorionic gonadotropin (hCG), placental lactogen (hPL) and placental growth factor (hPLGF) secretion, protein expression and immunolocalization. Additionally, the action of PAH mixtures on basal

Leflunomide is contraindicated in pregnant women, yet human data from leflunomide-exposed pregnancies do not indicate an embryofetal toxicity signal. The objective of the present analysis was to report pregnancy outcomes for leflunomide-exposed pregnancies in clinical trials and in the post-marketing setting. Pregnancy outcomes are summarized from leflunomide clinical trials and the post-marketing

Our objective was to determine if maternal first trimester urinary phthalate concentrations are associated with reduced penile length (PL) or width (PW) at birth in full term singletons. First trimester phthalate metabolite urinary concentrations were obtained from mothers participating in a Canadian pregnancy cohort study (MIREC). PL and PW were measured shortly after birth in the male offspring.

After the phase-out of polybrominated diphenyl ethers, their replacement compounds, organophosphate flame retardants (OPFRs) became ubiquitous in home and work environments. OPFRs, which may act as endocrine disruptors, are detectable in human urine, breast milk, and blood samples collected from pregnant women. However, the effects of perinatal OPFR exposure on offspring homeostasis and gene expression

Phthalates and environmental phenols might be associated with some benign diseases that have been found to be hormone-sensitive. Current knowledge on adverse effects of these chemicals among reproductive women is limited and often controversial. Therefore, the purpose of this study was to investigate the association between the urinary concentration of phthalates and environmental phenols and gynecological

Developmental toxicity is defined as the occurrence of adverse effects on the developing organism as a result from exposure to a toxic agent. These alterations can have long-term acute effects. Current in vitro models present important limitations and the evaluation of toxicity is not entirely objective. In silico methods have also shown limited success, in part due to complex and varied mechanisms

Many reports describe an association between preconceptional paternal exposure to environmental chemicals, including the persistent organic pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) with an increased number of female offspring. We chronically treated wild-type C57BL/6 male mice with TCDD to investigate a role for the aryl hydrocarbon receptor (AHR) transcription factor. These mice had a

This study was designed to demonstrate disorder of hypothalamic-pituitary-adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration and dysfunction of glucose and lipid metabolism induced by prenatal ethanol exposure (PEE) in postnatal week 40 (PW40) female offspring rats. Pregnant Wistar rats were administrated 4  g/kg·d ethanol intragastrically from gestational day 11 until term

Gestational vitamin D deficiency is associated with pulmonary diseases. This study aimed to investigate the effect of gestational vitamin D deficiency on fetal lung development in mice. Absolute and relative weights of fetal lungs were reduced in vitamin D deficient (VDD) group. Incrassate mesenchyme, measured by septal wall thickness, accompanied by lessened saccular space, was shown in VDD group

Recent reports indicate that 7% of pregnant mothers in North America use cannabis. This is concerning given that in utero exposure to Δ9-tetrahydrocannabinol (Δ9-THC), the main psychoactive component in cannabis, causes fetal growth restriction and may alter replication and survival of pancreatic β-cells in the offspring. Accordingly, we hypothesized that maternal exposure to Δ9-THC during pregnancy

As U.S. states steadily legalize its distribution and the prevalence of its use in people of reproductive age continues to rise, the need to understand the effects of marijuana on human physiology is becoming increasingly urgent. While marijuana is well-known for its psychoactive effects and applications in controlling pain and nausea, little is known about its effects on reproduction. This review

Fipronil (FPN) is a widely used phenylpyrazole pesticide for the control of insects and removal of veterinary pet fleas, ticks, etc. Although FPN presents moderate hazards to human health, people are readily exposed in daily life. FPN acts by impairing the central nervous systems of insects by blocking gamma-aminobutyric acid (GABA) and glutamate-activated chloride channels. A previous study demonstrated

Prenatal exposure to organic pollutants increases the risk of low birth weight (LBW) offspring. Women involved in the plucking of tea leaves can be exposed to polycyclic aromatic hydrocarbons (PAHs) during pregnancy through inhalation and diet. Therefore, the aim of the study was to investigate the association of maternal socio-demographic features and blood PAH concentration with LBW; also to develop

Exposure to the man-made chemicals perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorohexanesulfonate (PFHxS) is widespread. These perfluoroalkyl substances (PFASs) have been associated with androgenic endocrine-disrupting properties; however, the evidence is equivocal and few human studies have examined the association between prenatal exposure to PFASs and markers of androgenic

Sperm DNA fragmentation index (SDF), as an important supplement to routine semen parameters, has been proposed to discriminate between fertile and infertile men, and predicts the outcomes of natural conception and in vitro fertilization. Unfortunately there are uncertainty and contradictory evidences regarding the importance of SDF. An important reason is the fact that significant and fundamental research

Kallikrein-kinin system (KKS) is involved in vascular reactivity and inflammatory response to cytotoxic drugs. Since cisplatin is a widely used chemotherapy and its cytotoxic mechanism can trigger inflammation and oxidative damage, in this work we evaluated the role of KKS in an animal model of cisplatin-induced ovarian toxicity. Biomarkers of ovarian stem cells, activity of KKS, inflammation and oxidative

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) in particulate matter that has a diameter of ≤2.5 μm (PM2.5). Studies have demonstrated that BaP exposure causes oocyte meiotic arrest in mice. However, whether BaP exposure also affects oocyte maturation in offspring remains unclear. To test this, female mice were administered BaP before pregnancy to generate BaP-exposed offspring. Our

Bisphenol S (BPS) is widely used to replace the known endocrine disruptor BPA in various products. We evaluated the effect of acute in vivo BPS exposure on oocyte quality, simulating the oral route of exposure via oral gavage. Eight-week-old ICR female mice (N = 15 per experimental group) were exposed to vehicle or BPS1–BPS4 (0.001, 0.1, 10, and 100 ng BPS x g bw−1 day−1, respectively) for seven days

Di(2-ethylhexyl) phthalate (DEHP) is a known endocrine disruptor and diisononyl phthalate (DiNP) is a common DEHP replacement chemical. However, little is known about late-life consequences due to DEHP or DiNP exposure during adulthood. Thus, this study tested the hypothesis that adult exposure to DEHP or DiNP affects female reproductive parameters during late-life in female mice. Female CD-1 mice

Exposure to trace metals may impact reproductive health outcomes through perturbations in maternal immune signaling molecules. We conducted a cross-sectional study of 390 pregnant women from the LIFECODES birth cohort and investigated the associations between 17 urinary metals and five immune biomarkers measured in the 3rd trimester (median 26 weeks gestation). We used linear regression to estimate

Cadmium is involved in female gonadal toxicity. Although many studies concur in suggesting a significant influence on female reproduction, the mechanisms of action are still needed to study. This study was designed to examine the characteristics of 0, 5, 10, and 20 μM cadmium toxicity in granulosa cells culture for 12 h, and the subsequent effect of cadmium exposure on AMH production and formation

Decidualization, which comprises proliferation and differentiation of endometrial stromal cells (ESCs), is essential for the establishment of a receptive endometrium and pregnancy to occur. A deregulation of decidualization has been associated with miscarriage, infertility and other pregnancy-related disorders. The role of estradiol (E2) on decidualization has already been shown, since it regulates

Congenital anomalies of the kidney and urinary tract (CAKUT) include a broad group of birth defects. Exposure to endocrine disrupting chemicals (EDCs) is suspected to be one of the risk factors for CAKUT, and the use of personal care products (PCPs) is a source of EDC exposure. Therefore, this study aimed to investigate the relationship between CAKUT and the use of PCPs in a large birth cohort study

Cigarette smoke (CS) has a negative impact on women's health and fertility. Studies have shown that histone deacetylases 1 and 2 (HDAC1/2) were involved in oocyte development. However, the roles of HDAC1/2 in ovarian toxicity caused by CS exposure and the therapeutic potential of trichostatin A (TSA, a HDAC inhibitor) for ovarian tissue damage have not been investigated. In this study, Female C57BL/6

Anethole is a natural anisole derivative that has been widely used in food and daily chemical industries, agricultural applications and the traditional medicine. It is closely related to aspects of daily life, and humans can easily be exposed to it. Although the reproductive toxicity of anethole was shown in the rat, its effect on human reproduction remains unknown. In this study, we examined the effect

This study investigates if Cu and Pb act as endocrine disruptors affecting endometrial cells. Primary EnSCs and EnECs were exposed to Cu (0, 50, 100 and 200 μM) or Pb (0, 30, 100 and 500 μM) and assessed for viability, decidualization, apoptosis and proliferation on EnSCs, and wound healing and adhesion capabilities on EnECs. Cu exposure decreased significantly cell viability in a dose-dependent manner

Increasing evidence reveals that a broad spectrum of environmental chemicals and pharmaceutical compounds cause female ovarian toxicity (ovotoxicity). The current gold standard of ovotoxicity testing largely relies on whole laboratory animals, but in vivo models are time consuming, costly, and present animal welfare concerns. We previously demonstrated that the 3D encapsulated in vitro follicle growth

Vitamin K antagonists (VKA) are not recommended during pregnancy because warfarin (a first-generation VKA) is associated with a malformation syndrome "the fetal warfarin syndrome" (FWS). VKA are also used for rodent management worldwide. Recently, the Committee for Risk Assessment responsible for the European chemical legislation for advances on the safe use of chemicals had classed 8 anticoagulant

Chronic kidney disease (CKD) affects over 15 % of the adults in the United States. Pregnant women with CKD present an additional challenge in that they are at increased risk for adverse events such as preterm birth. Exposure to environmental toxicants, such as methylmercury, may exacerbate maternal disease and increase the risk of adverse fetal outcomes. We hypothesized that fetuses of mothers with

Phthalates are commonly used plasticizers and additives that are found in plastic containers, children's toys and medical equipment. Phthalates are classified as endocrine-disrupting chemicals and exposure to phthalates has been associated with several human health risks including reproductive defects. Most studies focus on a single phthalate; however, humans are exposed to a mixture of phthalates

Fetal rat exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduces epididymal sperm number involving altered pituitary-testicular hormonal signaling as the proposed mode-of-action (MOA). To evaluate this MOA and compare TCDD to 2,3,7,8-tetrachlorodibenzofuran (TCDF), an in utero rat exposure and study was conducted. Endpoints included congener tissue levels and transcriptomes of maternal liver

Polybrominated diphenyl ethers (PBDEs) are flame retardant compounds detected in human placenta and linked to adverse pregnancy outcomes. Impaired trophoblast migration and invasion during early pregnancy have been implicated as potential mechanisms of pregnancy disorders. The present study investigated the effect of BDE-47, a prevalent PBDE congener, on cell migration, invasion, and matrix metalloproteinase

The endogenous opioid peptides have been reported to be involved in the regulation of reproductive physiology. Many of the studies conclude with sentences around the harmful effect of opioids in male fertility but, actually, there is only one study regarding the real fertility potential of spermatozoa that have been exposed to mu specific opioids. The aim of the present study was to see if the modulation

While for decades attention deficit hyperactivity disorder (ADHD) was regarded as mostly a pediatric condition, it is apparent that many adults continue to be afflicted by this condition, and presently an estimated 30 %–40 % of patients continue with ADHD symptomatology into adulthood. With more adults using stimulants for ADHD, there is evidence of increased numbers using ADHD medications in pregnancy

Prenatal and postnatal exposure to cocaine can affect the development and function of the central nervous system in offspring. It also produces changes in cocaine-induced dopamine release and increases cocaine self-administration and cocaine-induced conditioned place preference. Further, prenatal cocaine exposure involves greater risk for development of a substance use disorder in adolescents. Therefore

Advanced glycation end products (AGEs) are products of cascades of non-enzymatic glycosylation. They are formed over a period of hours to days, depending on the protein lifetime. AGEs acts by independently producing reactive oxygen species (ROS) or by binding to their receptors. Binding of AGE to the receptor for advanced glycation end products (RAGE) has been shown to play a role in physiological

17α-ethynylestradiol (EE2), a synthetic hormone that derives from the natural hormone estradiol, has been reported to alter the sex determination, sexual maturity and secondary sexual characteristics of exposed organisms. However, the adverse effects of EE2 on the oocyte quality have not fully determined. Here, we found that EE2 exposure compromised the fertilization capacity of mouse oocytes, while

Nuclear receptors (NRs) rapidly activate/repress gene expression to detour immune responses and allow tissue adaptation to constant environmental changes. However, the effect of combined NRs in the immune system is often unclear due to the lack of reliable experimental models that recapitulate the complex interaction between NRs in vivo. Here, we used the zebrafish to investigate the immunological

Endocrine disruption continues to be a matter of high concern, and a subject of intensive activities at the public, political, regulatory and academic levels. Currently, available regulatory test guidelines (TGs) relevant to the identification of endocrine disrupters are largely limited to estrogen, androgen, thyroid and steroidogenesis (EATS) pathways. Thus, there is an increasing interest and need

The framework for developmental toxicity testing has remained largely unchanged for over 50 years and although it remains invaluable in assessing potential risks in pregnancy, knowledge gaps exist, and some outcomes do not necessarily correlate with clinical experience. Advances in omics, in silico approaches and alternative assays are providing opportunities to enhance our understanding of embryo-fetal

In order to better explain, predict, or extrapolate to humans the developmental toxicity effects of chemicals to zebrafish (Danio rerio) embryos, we developed a physiologically-based pharmacokinetic (PBPK) model designed to predict organ concentrations of neutral or ionizable chemicals, up to 120 hours post-fertilization. Chemicals' distribution is modeled in the cells, lysosomes, and mitochondria

The general population, including children and adolescents, is exposed to 4-methylimidazole (4-MI) in the diet. 4-MI is a by-product of caramel color manufacturing. It has been previously classified as a possible human carcinogen and displays potential reproductive toxicity. A follow up assessment of reproductive toxicity was conducted in rats utilizing the reproductive assessment by continuous breeding