Delayed adverse effects of neonatal exposure to polymeric nanoparticle poly(ethylene glycol)-block-polylactide methyl ether on hypothalamic–pituitary–ovarian axis development and function in Wistar rats

Rollerová, Eva; Jurčovičová, J; Mlynarčíková, Alžbeta Bujňáková; Sadlonová, I; Bilaničová, Dagmar; Wsólová, Ladislava; Kiss, Alexander; Kovrižnych, Jevgenij; Kronek, Juraj; Cĭampor, F; Vávra, I.; Scsuková, Soňa

doi:10.1016/j.reprotox.2015.07.072

Cited by 34 publications

(30 citation statements)

References 58 publications

(85 reference statements)

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“…In their study, NPs crossed the blood-brain barrier and accumulated in the central nervous system (CNS) [59]. Later, NPs disrupted hormone secretion, such as gonadotropin-releasing hormone (GnRH), which is responsible for oogenesis, through the hypothalamic-pituitary-gonadal axis [60][61][62]. Moreover, NPs could also cross through the placenta into the fetus, causing treated mice to likely exhibit fetal inflammation, genotoxicity, apoptosis, reproductive deficiency, and immunodeficiency [60].…”

Section: Reproductive Toxicity Of Ps-npsmentioning

confidence: 99%

Nanoplastics Cause Neurobehavioral Impairments, Reproductive and Oxidative Damages, and Biomarker Responses in Zebrafish: Throwing up Alarms of Wide Spread Health Risk of Exposure

Sarasamma

Audira

Siregar

et al. 2020

IJMS

233

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Plastic pollution is a growing global emergency and it could serve as a geological indicator of the Anthropocene era. Microplastics are potentially more hazardous than macroplastics, as the former can permeate biological membranes. The toxicity of microplastic exposure on humans and aquatic organisms has been documented, but the toxicity and behavioral changes of nanoplastics (NPs) in mammals are scarce. In spite of their small size, nanoplastics have an enormous surface area, which bears the potential to bind even bigger amounts of toxic compounds in comparison to microplastics. Here, we used polystyrene nanoplastics (PS-NPs) (diameter size at ~70 nm) to investigate the neurobehavioral alterations, tissue distribution, accumulation, and specific health risk of nanoplastics in adult zebrafish. The results demonstrated that PS-NPs accumulated in gonads, intestine, liver, and brain with a tissue distribution pattern that was greatly dependent on the size and shape of the NPs particle. Importantly, an analysis of multiple behavior endpoints and different biochemical biomarkers evidenced that PS-NPs exposure induced disturbance of lipid and energy metabolism as well as oxidative stress and tissue accumulation. Pronounced behavior alterations in their locomotion activity, aggressiveness, shoal formation, and predator avoidance behavior were exhibited by the high concentration of the PS-NPs group, along with the dysregulated circadian rhythm locomotion activity after its chronic exposure. Moreover, several important neurotransmitter biomarkers for neurotoxicity investigation were significantly altered after one week of PS-NPs exposure and these significant changes may indicate the potential toxicity from PS-NPs exposure. In addition, after ~1-month incubation, the fluorescence spectroscopy results revealed the accumulation and distribution of PS-NPs across zebrafish tissues, especially in gonads, which would possibly further affect fish reproductive function. Overall, our results provided new evidence for the adverse consequences of PS-NPs-induced behavioral dysregulation and changes at the molecular level that eventually reduce the survival fitness of zebrafish in the ecosystem.

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Section: Reproductive Toxicity Of Ps-npsmentioning

confidence: 99%

Nanoplastics Cause Neurobehavioral Impairments, Reproductive and Oxidative Damages, and Biomarker Responses in Zebrafish: Throwing up Alarms of Wide Spread Health Risk of Exposure

Sarasamma

Audira

Siregar

et al. 2020

IJMS

233

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“…Th e micelle dispersion resulted in size distribution with two main peaks of secondary particle sizes, averaged as 64.9±10.5 nm and 911.4±177.6 nm, what indicates that the PEG-b-PLA micelles were aggregated in solution. Th e PEG-b-PLA micelles were stable for 24 h at ambient temperature as monitored by TEM (for details see Rollerova et al 2015a).…”

Section: Resultsmentioning

confidence: 99%

“…Zeta potential was measured by Nicomp Submicron Particle Sizer Autodilute Model 380 (Santa Barbara, CA, USA) using the electrophoretic light scattering (ELS) method. Size distribution of PEG-b-PLA was evaluated by dynamic light scattering (DLS) with a NICOMP TM 380 ZLS Particle Sizer (Santa Barbara, CA, USA) (for details see Rollerova et al 2015a).…”

Section: Methodsmentioning

confidence: 99%

“…We have previously shown that neonatal exposure to PEG-b-PLA NPs (20, 40 mg/kg b.w.) may induce delayed adverse eff ects on hypothalamic-pituitary-ovarian axis development (accelerated onset of vaginal opening) and function [reduced number of regular estrous cycles, altered course of hypothalamic gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) secretion, and increased progesterone serum levels] in 6-month-old female rats (Rollerova et al 2015a). In addition, neonatal treatment with PEG-b-PLA NPs (20 mg/kg b.w.)…”

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confidence: 99%

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Adverse eff ects of polymeric nanoparticle poly(ethylene glycol)- block-polylactide methyl ether (PEG-b-PLA) on steroid hormone secretion by porcine granulosa cells

Scsuková

Bujnakova

Kiss

et al. 2017

Endocrine Regulations

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Objectives. Development of nanoparticles (NPs) for biomedical applications, including medical imaging and drug delivery, is currently undergoing a dramatic expansion. Diverse eff ects of diff erent type NPs relating to mammalian reproductive tissues have been demonstrated. Th e objective of this study was to explore the in vitro eff ects of polymeric nanoparticle poly(ethylene glycol)-blockpolylactide methyl ether (PEG-b-PLA NPs) on functional state and viability of ovarian granulosa cells (GCs), which play an important role in maintaining ovarian function and female fertility.Methods. Th e GCs isolated from porcine ovarian follicles were incubated with the diff erent concentrations of PEG-b-PLA NPs (PEG average Mn=350 g/mol and PLA average Mn=1000 g/mol; 0.2-100 μg/ml) or poly(ethylene glycol) with an average molecular weight of 300 (PEG-300; 0.2-40 mg/ml) in the presence or absence of stimulators, follicle-stimulating hormone (FSH; 1 μg/ml), androstenedione (100 nM), forskolin (10 μM) or 8Br-cAMP (100 μM), for diff erent time periods (24, 48, 72 h). At the end of the incubation, progesterone and estradiol levels produced by GCs were measured in the culture media by radioimmunoassay. Th e viability of GCs was determined by the method using a colorimetric assay with MTT.Results. Treatment of GCs with PEG-b-PLA NPs induced a signifi cant decrease in basal as well as FSH-stimulated progesterone secretion above the concentration of 20 and 4 μg/ml, respectively. Moreover, PEG-b-PLA NPs reduced forskolin-stimulated, but not cAMP-stimulated progesterone production by GCs. A dose-dependent inhibition of androstenedione-stimulated estradiol release by GCs was found by the action of PEG-b-PLA NPs. Incubation of GCs with PEG-300 significantly inhibited basal as well as FSH-stimulated progesterone secretion above the concentration of 40 mg/ml. PEG-b-PLA NPs and PEG-300 signifi cantly reduced the viability of GCs at the highest tested concentrations (100 μg/ml and 40 mg/ml, respectively).Conclusions. Th e obtained results indicate that polymeric NPs PEG-b-PLA might induce alterations in steroid hormone production by ovarian GCs and thereby could modify reproductive functions.

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“…The results of recent studies have reported that NPs may pose adverse effects on male and female reproductive health by altering normal testis and ovarian structure, spermatogenesis and sperm quality, oogenesis, follicle maturation and sex hormone levels (Taylor et al 2012;Iavicoli et al 2013;Larson et al 2014;Hou and Zhu 2017). The adverse effects of polymeric NPs have not been extensively studied and only few studies have focused on their effects on reproductive system to date (Rollerova et al 2015a;Scsukova et al 2015Scsukova et al , 2017. Numerous studies to date have demonstrated that TiO 2 NPs penetrates through the digestive system and possibly the blood circulation, leading to accumulation in the ovary and consequent reproductive toxicity (Shi et al 2013;Das et al 2016;Alaee et al 2017;Hong et al 2017).…”

mentioning

confidence: 99%

The use of ex vivo ovary culture for assessment of alterations in steroidogenesis following neonatal exposure to poly(ethylene glycol)-block-polylactide methyl ether or titanium dioxide nanoparticles in Wistar rats

Scsuková

Mlynarčíková

Rollerová

2020

Endocrine Regulations

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Objectives. Rapid development and widespread application of different types of nanoparticles (NPs) may result in increased exposure of humans and animals to NPs. Recently, reproductive toxicity due to NP exposure has become a major component of risk assessment. Current data have suggested that NPs may pose adverse effects on male and female reproductive health by altering normal testis and ovarian structure, and sex hormone levels. To detect possible alterations in steroidogenesis in adult and infantile rats following neonatal exposure to polymeric poly(ethylene glycol)-block-polylactide methyl ether (PEG-b-PLA) or titanium dioxide (TiO2) NPs, whole ovary cultures were used.Methods. Newborn female Wistar rats were intraperitoneally (i.p.) injected daily with two different doses of PEG-b-PLA NPs (20 and 40 mg/kg body weight, b.w.) or TiO2 NPs (1% LD50 TiO2=59.2 µg/kg b.w. and 10% LD50 TiO2=592 µg/kg b.w.) from postnatal day 4 (PND 4) to PND 7. The ovaries were collected on PND73 and PND15 of PEG-b-PLA- and TiO2 NP-treated rats, respectively, and their corresponding control animals. Minced ovaries were cultured in vitro in the absence (basal conditions) or presence of gonadotropins (follicle-stimulating hormone, FSH and luteinizing hormone, LH) and insulin-like growth factor-1 (IGF-1) (stimulated conditions) for 6 days. At indicated time intervals, culture media were collected for steroid hormone (progesterone, estradiol) analysis by specific radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) kits.Results. Basal progesterone and estradiol secretion by ovaries from adult rats (PND73) were significantly decreased (p<0.01) in both PEG-b-PLA-treated groups after 3 days and 1 day of ex vivo ovary culture, respectively, compared with control group. With the presence of FSH/LH and IGF-1 in the culture medium, progesterone and estradiol production significantly increased (p<0.001) compared to basal levels. Stimulated progesterone production was significantly decreased (p<0.05) in PEG-b-PLA40-treated group after 3 days of culture compared with controls. After ex vivo culture of rat ovaries collected on PND15, basal progesterone and estradiol levels measured in the culture media did not differ between control and both TiO2 NP-treated groups. The ovaries from rats neonatally exposed to both doses of TiO2 NPs failed to respond to FSH/IGF stimulation in progesterone secretion at all time intervals.Conclusions. The obtained results indicate that neonatal exposure to NPs in female rats may alter ovarian steroidogenic output (steroid hormone secretion) and thereby might subsequently induce perturbation of mammalian reproductive functions. Possible mechanisms (induction of oxidative stress, inflammation) of adverse effects of NPs on ovarian function should be further elucidated.

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Delayed adverse effects of neonatal exposure to polymeric nanoparticle poly(ethylene glycol)-block-polylactide methyl ether on hypothalamic–pituitary–ovarian axis development and function in Wistar rats

Cited by 34 publications

References 58 publications

Nanoplastics Cause Neurobehavioral Impairments, Reproductive and Oxidative Damages, and Biomarker Responses in Zebrafish: Throwing up Alarms of Wide Spread Health Risk of Exposure

Nanoplastics Cause Neurobehavioral Impairments, Reproductive and Oxidative Damages, and Biomarker Responses in Zebrafish: Throwing up Alarms of Wide Spread Health Risk of Exposure

Adverse eff ects of polymeric nanoparticle poly(ethylene glycol)- block-polylactide methyl ether (PEG-b-PLA) on steroid hormone secretion by porcine granulosa cells

The use of ex vivo ovary culture for assessment of alterations in steroidogenesis following neonatal exposure to poly(ethylene glycol)-block-polylactide methyl ether or titanium dioxide nanoparticles in Wistar rats

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