The Production of Testosterone and Gene Expression in Neonatal Testes of Rats Exposed to Diisoheptyl Phthalate During Pregnancy is Inhibited.
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ABSTRACT:
SUBMITTER: Ji B
PROVIDER: S-EPMC8072358 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Acrolein has been reported to have diverse toxic effects on various organs, including the reproductive system. However, little is known regarding the effects of maternal acrolein exposure on testicular steroidogenesis in male offspring. The present study investigated the effects of acrolein on fetal testosterone production and associated genes. Pregnant Sprague?Dawley rats were intraperitoneally injected with vehicle (normal saline) or 1, 2 or 5 mg/kg acrolein from gestational day (GD) 14?20, and fetal testes were examined on GD 21. Fetal body and testicular weights were markedly reduced in pups following exposure to high doses of acrolein (5 mg/kg) in late pregnancy. Notably, in utero exposure of 5 mg/kg acrolein significantly decreased the testicular testosterone level and downregulated the expression levels of steroidogenic acute regulatory protein (StAR) and 3??hydroxysteroid dehydrogenase (3??HSD), whereas the levels of other steroidogenic enzymes, including scavenger receptor class B, cholesterol side?chain cleavage enzyme and steroid 17 alpha?hydroxylase/17,20 lyase, were unaffected. Furthermore, the 3??HSD immunoreactive area in the interstitial region of the fetal testes was reduced at a 5 mg/kg dose, whereas the protein expression levels of 4?hydroxynonenalwere dose?dependently increased following maternal exposure to acrolein. mRNA expression levels of insulin?like factor 3, a critical gene involved in testicular descent, were unaltered following maternal acrolein exposure. Taken together, the results of the present study suggested that maternal exposure to high doses of acrolein inhibited fetal testosterone synthesis, and abnormal expression of StAR and 3??HSD may be associated with impairment of the steroidogenic capacity.
| S-EPMC5482093 | biostudies-literature
Project description:The pharmaceutical 17α-ethynylestradiol (EE2) is considered as an endocrine-disrupting chemical that interferes with male reproduction and hormonal activation. In this study, we investigated the molecular mechanism underlying EE2-regulatory testosterone release in vitro and in vivo. The results show that EE2 treatment decreased testosterone release from rat Leydig cells. Treatment of rats with EE2 reduced plasma testosterone levels and decreased the sensitivity of human chorionic gonadotropin (hCG). EE2 reduced luteinizing hormone receptor (LHR) expression associated with decreased cAMP generation by downregulation of adenylyl cyclase activity and decreased intracellular calcium-mediated pathways. The expression levels of StAR and P450scc were decreased in Leydig cells by treatment of rats with EE2 for 7 days. The sperm motility in the vas deferens and epididymis was reduced, but the histopathological features of the testis and the total sperm number of the vas deferens were not affected. Moreover, the serum dihydrotestosterone (DHT) level was decreased by treatment with EE2. The prostate gland and seminal vesicle atrophied significantly, and their expression level of 5α-reductase type II was reduced after EE2 exposure. Taken together, these results demonstrate an underlying mechanism of EE2 to downregulate testosterone production in Leydig cells, explaining the damaging effects of EE2 on male reproduction.
| S-EPMC6994641 | biostudies-literature
Project description:Phthalate esters (PEs) constitute a large class of compounds that are used for many consumer product applications. Many of the C2-C7 di-ortho PEs reduce fetal testicular hormone and gene expression levels in rats resulting in adverse effects seen later in life but it appears that relatively large reductions in fetal testosterone (T) levels and testis gene expression may be required to adversely affect reproductive development (Hannas, B. R., Lambright, C. S., Furr, J., Evans, N., Foster, P. M., Gray, E. L., and Wilson, V. S. (2012). Genomic biomarkers of phthalate-induced male reproductive developmental toxicity: a targeted RT-PCR array approach for defining relative potency. Toxicol. Sci. 125, 544-557). The objectives of this study were (1) to model the relationships between changes in fetal male rat plasma testosterone (PT), T levels in the testis (TT), T production (PROD), and testis gene expression with the reproductive malformation rates, and (2) to quantify the "biologically relevant reductions" (BRRs) in fetal T necessary to induce adverse effects in the offspring. In the fetal experiment, Harlan Sprague-Dawley rats were dosed with dipentyl phthalate (DPeP) at 0, 11, 33, 100, and 300?mg/kg/day from gestational days (GD) 14-18 and fetal testicular T, PT levels, and T Prod and gene expression were assessed on GD 18. In the postnatal experiment, rats were dosed with DPeP from GD 8-18 and reproductive development was monitored through adulthood. The dose-response curves for TT levels (ED(50)?=?53?mg/kg) and T PROD (ED(50)?=?45?mg/kg) were similar, whereas PT was reduced at ED50 = 19?mg/kg. When the reductions in TPROD and Insl3 mRNA were compared with the postnatal effects of in utero DPeP, dose-related reproductive alterations were noted when T PROD and Insl3 mRNA were reduced by >45% and 42%, respectively. The determination of BRR levels may enable risk assessors to utilize fetal endocrine data to help establish points of departure for quantitative risk assessments.
| S-EPMC4715258 | biostudies-literature
Project description:To examine associations between phthalate metabolite urinary concentrations during early pregnancy and blood glucose levels obtained at the time of screening for gestational diabetes mellitus (GDM).Upon initiation of prenatal care, women with a mean gestational age of 12.8 weeks were recruited for a study of environmental chemical exposures (n = 110) and provided a spot urinary specimen. Blood glucose concentrations (mg/dl) were obtained from the electronic medical record for those patients who did not experience a pregnancy loss and did not transfer care to another facility prior to glucose screening (n = 72). Urinary concentrations of nine phthalate metabolites and creatinine were measured at the US Centers for Disease Control and Prevention. Associations between tertiles of phthalate metabolites concentrations and blood glucose levels were estimated using linear regression.Compared to pregnant women in the lowest concentration tertile, women with the highest urinary concentrations (? 3 rd tertile) of mono-iso-butyl phthalate (tertile: ? 15.3 ?g/l, ? = -18.3, 95% CI: -35.4, -1.2) and monobenzyl phthalate (tertile: ? 30.3 ?g/l, ? = -17.3, 95% CI: -34.1, -0.4) had lower blood glucose levels at the time of GDM screening after adjustment for urinary creatinine and demographic covariates.Because maternal glucose levels increase during pregnancy to provide adequate nutrition for fetal growth and development, these findings may have implications for fetal health. However, given the limitations of our study, findings should be interpreted cautiously.
| S-EPMC4724204 | biostudies-other
Project description:The purpose of this study is to assess pregnancy outcomes of women treated with a novel neuraminidase inhibitor, laninamivir, during pregnancy.A retrospective review of pregnancy outcomes of 112 pregnant women who were given laninamivir for treatment of influenza was performed. Possible adverse events, including miscarriages, preterm birth, foetal malformation and any neonatal morbidity requiring treatment, were assessed.Seventeen, 39, 46 and 10 women were administered a single inhaled dose of 20 or 40?mg of laninamivir at gestational week (GW) 3-11, 12-21, 22-36 and 37 or more, respectively. One (1.8%) of 56 women with laninamivir at GW <22 experienced miscarriage at GW <12. The remaining 111 women gave birth to 111 viable infants but at preterm (GW <37) in nine (8.8%) of 102 women with laninamivir at GW <37. Three (2.7%) of the 111 newborns had malformations: forefoot varus deformity, foot polydactyly and cleft lip in one each born to a mother taking laninamivir at GW 6, 17 and 21, respectively. Five neonates (4.5%) were small for gestational age. Eleven (9.9%), five (4.5%) and no neonates required phototherapy for jaundice, transient respiratory supports for respiratory distress syndrome (n?=?2) or transient tachypnoea of the newborn (n?=?3), and glucose administration for hypoglycaemia, respectively.Although this study included a small number of study women and no control women, the results suggested that maternal exposure to laninamivir did not increase the rate of adverse pregnancy and foetal outcomes.
| S-EPMC4265256 | biostudies-literature
Project description:BackgroundPrenatal exposures to phthalates and bisphenols are associated with impaired brain development in animals. However, epidemiological studies investigating the association between prenatal phthalate or bisphenol exposure and cognition have produced mixed findings and mostly had modest sample sizes and measured the exposure during the third trimester.ObjectiveWe examined the association between pregnancy maternal urinary biomarkers of phthalate or bisphenol exposure and nonverbal intelligence quotient (IQ) in children 6 years of age.MethodThe study sample consisted of 1,282 mother-child pairs participating in the Generation R Study, a population-based birth cohort in Rotterdam, Netherlands (enrollment 2002-2006). We measured maternal urinary concentrations of 18 phthalate metabolites and 8 bisphenols at <18, 18-25, and >25 wks of gestation. Child nonverbal IQ was measured at 6 years of age using the Snijders-Oomen Nonverbal Intelligence Test-Revised. Linear regression models were fit for each of the three collection phases separately, the three collection phases jointly, and for the averaged prenatal exposure across pregnancy.ResultsHigher urinary concentrations of phthalate metabolites during early pregnancy were associated with lower child nonverbal IQ score [e.g., B per 10-fold increase in summed low-molecular weight phthalates=-1.7 (95% CI: -3.1, -0.3)]. This association remained unchanged when adjusted for mid and late pregnancy exposures. We also observed an inverse association between late pregnancy di-n-octyl phthalate (DNOP) exposure and nonverbal IQ. Maternal urinary concentrations of bisphenols were not associated with child nonverbal IQ. There was no effect estimate modification by sex.ConclusionsWe did not observe that maternal biomarkers of bisphenol exposure are associated with nonverbal IQ. We found that phthalate exposure in early pregnancy and DNOP exposure in late pregnancy are associated with lower nonverbal IQ scores in children. Our results might suggest that particularly early pregnancy is a sensitive window of phthalate exposure, but future studies are needed to replicate our findings. https://doi.org/10.1289/EHP6047.
| S-EPMC7384796 | biostudies-literature
Project description:Cadmium (Cd) is an environmental carcinogenic pollutant known to inactivate several proteins involved in DNA repair systems while at the same time creating an oxidative stress that can result in additional DNA lesions. The testis and the lung are the target organs for cadmium carcinogenesis. Increased production of oxidants in vivo can cause damage to intracellular macromolecules such as DNA, proteins and lipids, which in turn lead to oxidative injury. So, this investigation aimed to evaluate the protective role of L-Carnitine through up regulation of HSPs against DNA damage induced by cadmium chloride. The current study was carried out on forty adult male rats, each with average weight 220-250g., were divided into 4 equal groups. 1(st) group was received saline solution (0.5 ml/100 g body weight) and kept as control. 2(nd) group was received 500mg / kg body weight L-Carnitine intraperitoneally (IP). 3(rd) group was administered 1.2 mg cadmium chloride IP. 4(th) group was received both cadmium chloride and L-Carnitine simultaneously. The comet assay parameters showed significantly increased HSP70 and DNA damage in testis cells after 10 and 56 days in the third group. Meanwhile, HSP70 showed significantly decreased levels after 10 days and 56 days in the fourth group after L-Carnitine treatment simultaneously with cadmium chloride. The results of the present study demonstrate a damaging effect of cadmium chloride on DNA of the testis cells (with low stress response). This damaging effect increases the synthesis of HSP70 that upregulated by L-Carnitine treatment and showed ameliorative effect of the cells for recovery.
| S-EPMC3282277 | biostudies-literature
Project description:BACKGROUND:Phthalates are known endocrine disruptors and peroxisome proliferator-activated receptor (PPAR) activators, potentially capable of promoting an obesogenic effect. Pregnant women are especially vulnerable to phthalate exposure due to physiological and metabolic changes during pregnancy, including those related to the metabolism of xenobiotics. Phthalate exposure during pregnancy has been associated with early gestational weight gain, however, its effect on long-term weight gain remains unclear. The aim of the present study was to evaluate the association between phthalate exposure during pregnancy and long-term changes in weight among women. METHODS:Urinary phthalate concentrations, socioeconomic, anthropometry and information on diet and socioeconomic status were collected during pregnancy from 178 women from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort. Maternal body weight and diet information was also collected up to 5 times in the first year postpartum and twice during follow-up visits 5.2-10.7 years later. A path analysis was performed to assess associations between urinary phthalate metabolite levels during pregnancy and change in weight (kg) per year after delivery, including age, education, living with/without partner, parity, daily energy intake and breastfeeding duration. RESULTS:The mean age at pregnancy was 27.3?±?5.9 years and mean body mass index during the first postpartum year was 27.07?±?4.22?kg/m2. On average, women gained 3.48?kg (0.52?±?0.84?kg/year). A unit increase in log-transformed mono-3-carboxypropyl phthalate (MCPP) was associated with 0.33?kg (95% CI: 0.09, 0.56) higher weight gain per year, and mono-benzyl phthalate (MBzP) with 0.21?kg (95% CI: -0.38, -0.03) lower weight gain per year. CONCLUSION:Exposure to certain phthalates during pregnancy may be associated with long-term weight change in women. More studies on the effects of phthalate exposure during pregnancy on women's long-term health are required.
| S-EPMC6347540 | biostudies-literature
Project description:BackgroundInsufficient or excessive gestational weight gain are associated with increased risks of adverse birth and childhood outcomes. Increasing evidence suggests that exposure to bisphenols and phthalates may disrupt hormonal pathways and thereby influence gestational weight gain.ObjectiveTo examine the associations of early and mid-pregnancy bisphenol and phthalate urine concentrations with gestational weight gain.MethodsIn a population-based prospective cohort study among 1,213 pregnant women, we measured early and mid-pregnancy bisphenol and phthalate urine concentrations. Maternal anthropometrics before pregnancy were obtained by questionnaire and repeatedly measured at our research center during pregnancy. We used linear and logistic regressions to evaluate the associations of bisphenols and phthalates with total and period-specific gestational weight gain.ResultsHigher maternal total bisphenols and bisphenol S were associated with a lower total gestational weight gain at nominal level. Stratification by body mass index group showed that higher total bisphenols and bisphenol S were associated with lower total gestational weight gain specifically in normal weight women (respectively -509 g [95% CI -819, -198] and -398 g [95% CI -627, -169]). Each log unit increase in early pregnancy total bisphenol and bisphenol A urine concentrations were associated with lower mid- to late pregnancy gestational weight gain in the whole group (effect estimates -218 g/log unit increase [95% CI -334, -102] and -132 g/log unit increase [95% CI -231, -34], respectively). These associations were independent of mid-pregnancy compounds. Mid-pregnancy bisphenols and phthalates concentrations were not associated with gestational weight gain.DiscussionHigher maternal bisphenol urine concentrations in early pregnancy may lead to reduced gestational weight in second half of pregnancy. Further research is needed to assess the effects of maternal bisphenols and phthalates urine concentrations on placental and fetal growth and development.
| S-EPMC8336629 | biostudies-literature
Project description:Background: Leydig cells secrete the steroid hormone, testosterone, which is essential for male fertility and reproductive health. Stress increases the secretion of glucocorticoid [corticosterone, (CORT) in rats] that decreases circulating testosterone levels in part through a direct action on its receptors in Leydig cells. Intratesticular CORT level is dependent on oxidative inactivation of CORT by 11?-hydroxysteroid dehydrogenase 1 (HSD11B1) in rat Leydig cells. Pain may cause the stress, thus affecting testosterone production in Leydig cells. Methods: Adult male Sprague-Dawley rats orally received vehicle control or 5 or 10 mg/kg dehydroepiandrosterone (DHEA) 0.5 h before being subjected to pain stimulation for 1, 3, and 6 h. In the present study, we investigated the time-course changes of steroidogenic gene expression levels after acute pain-induced stress in rats and the possible mechanism of DHEA that prevented it. Plasma CORT, luteinizing hormone (LH), and testosterone (T) levels were measured, and Leydig cell gene expression levels were determined. The direct regulation of HSD11B1 catalytic direction by DHEA was detected in purified rat Leydig, liver, and rat Hsd11b1-transfected COS1 cells. Results: Plasma CORT levels were significantly increased at hour 1, 3, and 6 during the pain stimulation, while plasma T levels were significantly decreased starting at hour 3 and 6. Pain-induced stress also decreased Star, Hsd3b1, and Cyp17a1 expression levels at hour 3. When 5 and 10 mg/kg DHEA were orally administered to rats 0.5 h before starting pain stimulation, DHEA prevented pain-mediated decrease in plasma T levels and the expression of Star, Hsd3b1, and Cyp17a1 without affecting plasma CORT levels. DHEA was found to modulate HSD11B1 activities by increasing its oxidative activity and decreasing its reductive activity, thus decreasing the intracellular CORT levels in Leydig cells. Conclusion: Stress induced by acute pain can inhibit Leydig cell T production by upregulation of corticosterone. DHEA can prevent the negative effects of excessive corticosterone by modulating HSD11B1 activity.
| S-EPMC5911460 | biostudies-literature