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

• Published in: Endocrine regulations (Bratislava) Vol. 54; no. 1; pp. 53 - 63
• Main Authors: Scsukova, Sona, Mlynarcikova, Alzbeta Bujnakova, Rollerova, Eva
• Format: Journal Article
• Language: English
• Published: Germany Sciendo 01-01-2020
• Subjects: Animals; Animals, Newborn; estradiol; Estradiol - metabolism; Female; Lactates - administration & dosage; Nanoparticles - administration & dosage; Nanoparticles - adverse effects; ovary; Ovary - drug effects; Ovary - metabolism; PEG; peg-b-pla; PLA; Polyethylene Glycols - administration & dosage; polymeric nanoparticles; progesterone; Progesterone - metabolism; Rats; Rats, Wistar; reproductive toxicity; Titanium - administration & dosage; titanium dioxide; ovary; polymeric nanoparticles; progesterone; reproductive toxicity; titanium dioxide; PEG-b-PLA; estradiol
• ISSN: 1336-0329; 1336-0329
• DOI: 10.2478/enr-2020-0007

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)-
-polylactide methyl ether (PEG-
-PLA) or titanium dioxide (TiO
) NPs, whole ovary cultures were used.
Newborn female Wistar rats were intraperitoneally (i.p.) injected daily with two different doses of PEG-
-PLA NPs (20 and 40 mg/kg body weight, b.w.) or TiO
NPs (1% LD50 TiO
=59.2 µg/kg b.w. and 10% LD50 TiO
=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 TiO
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.
Basal progesterone and estradiol secretion by ovaries from adult rats (PND73) were significantly decreased (p<0.01) in both PEG-
-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-
-PLA40-treated group after 3 days of culture compared with controls. After
culture of rat ovaries collected on PND15, basal progesterone and estradiol levels measured in the culture media did not differ between control and both TiO
NP-treated groups. The ovaries from rats neonatally exposed to both doses of TiO
NPs failed to respond to FSH/IGF stimulation in progesterone secretion at all time intervals.
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.