62
toxic, therefore, the dissolution was not considered to be responsible for the side
effects. Nanoparticulated zinc oxide showed dose-dependent lethality in human
sperm after in vitro exposure, and caused DNA damage and arrest in S-phase of a
spermatocytes cell line (Liu et al. 2016b; Barkhordari et al. 2013).
Endocrine disruptors were tested with a recent assay, involving two cell lines,
each of them representing the Leydig and the Sertoli cells (Farcal et al. 2015). These
are two types of testicular, non-germinal cells, important for the function and
architecture of the male gonad. The Sertoli cells, responsive to the pituitary folliclestimulating hormone, support and nourish the maturing gametes and build up the
blood-to-testis biological barrier, and the Leydig cells, positioned in the space
between the tubules, secrete the testosterone. The golden nanorods damaged the
blood-to-testis barrier through a damaged mitochondrial pathway of glycine.
Altered mitochondrial membrane permeability and transmembrane potential were
observed together with disrupted expression of several proteins bound to membrane
function (Xu et al. 2014a). Zinc oxide and silver nanoparticles were the most toxic
against these cells. At low concentration (10 μg/ml), the zinc oxide nanoparticles
were lethal (Farcal et al. 2015); at sublethal doses, they entered the cytoplasm and
the nucleus, reduced the membrane integrity and the viability, and increased the
apoptosis (Han et al. 2016b). Apoptosis and death of Sertoli cells followed the
oxidative stress caused by the exposure to silver nanoparticles or to nanocrystals of
copper sulfide, which produced photothermal and photodynamic lethal effects, in
agreement with what was observed in vivo (Han et al. 2016a, b; Liu et al. 2015).
Titanium dioxide nanoparticles gave contrasting results, in studies on Sertoli and
Leydig cell lines. In the tiered protocol adopted by Farcal et al. (2015), the safe
concentration was lower than 100 μg/l. Other studies, however, demonstrated a
dose-dependent increase of mitochondrial damage in the Sertoli cell lines, with
apoptosis and death. The suggested mechanism of cytotoxicity seemed to be
mediated by the calcium-regulated cascade inducing inflammatory cytokines (Hong
et al. 2016; Ye et al. 2017).
The carbon black, which slightly induced the aromatase expression in Leydig
cell lines without affecting vitality, was a fair endocrine disruptor (Komatsu
et al. (2008).
Organic nanoparticles, functionalized with the follicle-stimulating hormone and
loaded with superoxide dismutase, counteracted the strong oxygenic stress produced
by hydrogen peroxide in the Sertoli cell lines (Snow-Lisy et al. 2014).
3.3 In Vitro Exposure of Eggs and Follicular Cells
of the Female Gonad
The functional female gonad is characterized by the periodical maturation of one or
more ovary follicles. The immature follicle contains the gamete in a crown of
granulosa cells. The mature follicle (antral) is a cystic formation, in which the
A. G. Cattaneo
toxic, therefore, the dissolution was not considered to be responsible for the side
effects. Nanoparticulated zinc oxide showed dose-dependent lethality in human
sperm after in vitro exposure, and caused DNA damage and arrest in S-phase of a
spermatocytes cell line (Liu et al. 2016b; Barkhordari et al. 2013).
Endocrine disruptors were tested with a recent assay, involving two cell lines,
each of them representing the Leydig and the Sertoli cells (Farcal et al. 2015). These
are two types of testicular, non-germinal cells, important for the function and
architecture of the male gonad. The Sertoli cells, responsive to the pituitary folliclestimulating hormone, support and nourish the maturing gametes and build up the
blood-to-testis biological barrier, and the Leydig cells, positioned in the space
between the tubules, secrete the testosterone. The golden nanorods damaged the
blood-to-testis barrier through a damaged mitochondrial pathway of glycine.
Altered mitochondrial membrane permeability and transmembrane potential were
observed together with disrupted expression of several proteins bound to membrane
function (Xu et al. 2014a). Zinc oxide and silver nanoparticles were the most toxic
against these cells. At low concentration (10 μg/ml), the zinc oxide nanoparticles
were lethal (Farcal et al. 2015); at sublethal doses, they entered the cytoplasm and
the nucleus, reduced the membrane integrity and the viability, and increased the
apoptosis (Han et al. 2016b). Apoptosis and death of Sertoli cells followed the
oxidative stress caused by the exposure to silver nanoparticles or to nanocrystals of
copper sulfide, which produced photothermal and photodynamic lethal effects, in
agreement with what was observed in vivo (Han et al. 2016a, b; Liu et al. 2015).
Titanium dioxide nanoparticles gave contrasting results, in studies on Sertoli and
Leydig cell lines. In the tiered protocol adopted by Farcal et al. (2015), the safe
concentration was lower than 100 μg/l. Other studies, however, demonstrated a
dose-dependent increase of mitochondrial damage in the Sertoli cell lines, with
apoptosis and death. The suggested mechanism of cytotoxicity seemed to be
mediated by the calcium-regulated cascade inducing inflammatory cytokines (Hong
et al. 2016; Ye et al. 2017).
The carbon black, which slightly induced the aromatase expression in Leydig
cell lines without affecting vitality, was a fair endocrine disruptor (Komatsu
et al. (2008).
Organic nanoparticles, functionalized with the follicle-stimulating hormone and
loaded with superoxide dismutase, counteracted the strong oxygenic stress produced
by hydrogen peroxide in the Sertoli cell lines (Snow-Lisy et al. 2014).
3.3 In Vitro Exposure of Eggs and Follicular Cells
of the Female Gonad
The functional female gonad is characterized by the periodical maturation of one or
more ovary follicles. The immature follicle contains the gamete in a crown of
granulosa cells. The mature follicle (antral) is a cystic formation, in which the
A. G. Cattaneo