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

Abstract

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.

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

“…Different superscripts indicate significant differences between groups. erova et al 2015a; Scsukova et al 2015;Dvorakova et al 2017;Scsukova et al 2017) or will be the subject of other articles. In the present paper, we present a part of these studies investigating possible alterations of ovarian steroidogenic capacity in adult (PND73) and infantile (PND15) rats neonatally (PND4-7) exposed to polymeric PEG-b-PLA and TiO 2 NPs, respectively, using ex vivo ovary cultures.…”

“…Moreover, PEGb-PLA NPs reduced forskolin-stimulated, but not cAMP-stimulated progesterone production by GCs. A dose-dependent inhibition of androstenedionestimulated estradiol release by GCs was found by the action of PEG-b-PLA NPs (Scsukova et al 2017).…”

“…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).…”

Advances in endocrine toxicity of nanomaterials and mechanism in hormone secretion disorders

“…Thus, further systematic investigation of possible endocrine influence afforded by polymeric NPs is warranted. They also found PEG‐b‐PLA NPs decreased the viability of porcine ovarian granulosa cells (GCs), and it may be through affecting FSH signaling at the membrane level PEG‐b‐PLA NPs reduced progesterone secretion (Scsukova et al, 2017). Another polymer nanomaterial, dendritic polyglycerol NPs (dPG‐NPs), has been shown to cause a decrease in HCG levels in placental explants, but not in BeWo cell and trophoblast monolayer cultures.…”