65
differed in murine mature cumulus–oocyte complexes and in those obtained after
hormonal stimulation from prepubertal goats, exposed during maturation. In the
first case, decreased fertilization rate and DNA damage followed the intake of
nanoparticles by the granulosa cells and the zona pellucida of the egg. In the ovine
cumulus instead, the nanoparticles entered the granulosa cells, not the oocyte, and
increased the growth and maturation of the zygote, reducing the oxidative stress
(Ariu et al. 2017; Préaubert et al. 2016). Arsenic trioxide is used for the chemotherapy
of lymphoma, and the nanoparticulate formulation performed better than the
traditional drug to protect the female fertility (Ahn et al. 2013).
The toxicity of gold nanoparticles seems to be low for the granulosa, while those
of silver are moderately toxic and inhibit the cumulus expansion, the oocyte
maturation, and second meiosis (Han et al. 2016a; Stelzer and Hutz 2009; Tiedemann
et al. 2014). The results strictly depend on experimental conditions. Organic coating,
protective against dissolution, quenched the high toxicity of quantum dots, which
reduced the fertilization rate of cumulus–oocyte complexes. The fluorescent signal
was high in the cells of mature follicles and in the sub-plasma membrane of oocytes,
but weaker in the cells of the cumulus (Feugang et al. 2015; Hsieh et al. 2009; Xu
et al. 2012, 2016b).
Among “soft” nanoparticles, the polymeric polyethylene glycole-polylactide
methyl ether reduced the viability of granulosa cells only at high doses and altered
the secretion of progesterone and estradiol. However, this result was not exclusive
to nanoparticles because the non-particulated polyethylene glycole behaved
similarly (Scsukova et al. 2017). Nanoparticles conjugated with follicle-stimulating
hormone or its derivative follicle-stimulating hormone33 (ovarian cancer specific
receptor), loaded with paclitaxel, were more precisely addressed to the tumor cells
and more efficient was the paclitaxel alone, also in nanoformulation (Fan et al.
2014; Zhang et al. 2009). Lipid-core nanoparticles were safe for cumulus–oocyte
complex; if loaded with melatonin, it reduced oxidative stress and enhanced meiotic
maturation, cleavage, and blastocyst production (Remião et al. 2016). The carbon
black reduced the aromatase expression and the production of estrogen (Simon
et al. 2017),
From these considerations, the toxicity of nanomaterials on the reproductive
components of the ovary seems to be low or moderate. In some cases, as drug or
drug carriers, they performed better than the corresponding traditional formulation.
3.4 The Placenta: A Differentiated Mother-to-Fetus
Biological Barrier in Mammals
The most useful model species for predicting toxicity in humans, as well as the
subjects of artificial fertilization in vitro, belong to mammals. The development of
mammals is unique because of the presence of a chorioallantoic placenta along the
fetal period. This powerful biological barrier is selective for several solutes and
3 Safety and Utility of Nanomaterials on Reproduction and Development: An Update…
differed in murine mature cumulus–oocyte complexes and in those obtained after
hormonal stimulation from prepubertal goats, exposed during maturation. In the
first case, decreased fertilization rate and DNA damage followed the intake of
nanoparticles by the granulosa cells and the zona pellucida of the egg. In the ovine
cumulus instead, the nanoparticles entered the granulosa cells, not the oocyte, and
increased the growth and maturation of the zygote, reducing the oxidative stress
(Ariu et al. 2017; Préaubert et al. 2016). Arsenic trioxide is used for the chemotherapy
of lymphoma, and the nanoparticulate formulation performed better than the
traditional drug to protect the female fertility (Ahn et al. 2013).
The toxicity of gold nanoparticles seems to be low for the granulosa, while those
of silver are moderately toxic and inhibit the cumulus expansion, the oocyte
maturation, and second meiosis (Han et al. 2016a; Stelzer and Hutz 2009; Tiedemann
et al. 2014). The results strictly depend on experimental conditions. Organic coating,
protective against dissolution, quenched the high toxicity of quantum dots, which
reduced the fertilization rate of cumulus–oocyte complexes. The fluorescent signal
was high in the cells of mature follicles and in the sub-plasma membrane of oocytes,
but weaker in the cells of the cumulus (Feugang et al. 2015; Hsieh et al. 2009; Xu
et al. 2012, 2016b).
Among “soft” nanoparticles, the polymeric polyethylene glycole-polylactide
methyl ether reduced the viability of granulosa cells only at high doses and altered
the secretion of progesterone and estradiol. However, this result was not exclusive
to nanoparticles because the non-particulated polyethylene glycole behaved
similarly (Scsukova et al. 2017). Nanoparticles conjugated with follicle-stimulating
hormone or its derivative follicle-stimulating hormone33 (ovarian cancer specific
receptor), loaded with paclitaxel, were more precisely addressed to the tumor cells
and more efficient was the paclitaxel alone, also in nanoformulation (Fan et al.
2014; Zhang et al. 2009). Lipid-core nanoparticles were safe for cumulus–oocyte
complex; if loaded with melatonin, it reduced oxidative stress and enhanced meiotic
maturation, cleavage, and blastocyst production (Remião et al. 2016). The carbon
black reduced the aromatase expression and the production of estrogen (Simon
et al. 2017),
From these considerations, the toxicity of nanomaterials on the reproductive
components of the ovary seems to be low or moderate. In some cases, as drug or
drug carriers, they performed better than the corresponding traditional formulation.
3.4 The Placenta: A Differentiated Mother-to-Fetus
Biological Barrier in Mammals
The most useful model species for predicting toxicity in humans, as well as the
subjects of artificial fertilization in vitro, belong to mammals. The development of
mammals is unique because of the presence of a chorioallantoic placenta along the
fetal period. This powerful biological barrier is selective for several solutes and
3 Safety and Utility of Nanomaterials on Reproduction and Development: An Update…