Long-lasting effects of lindane on mouse spermatogenesis induced by in utero exposure

Traina, M.E.; Rescia, Michele; Urbani, Elisabetta; Mantovani, Alberto; Macrı̀, Caterina; Ricciardi, Claudio; Stazi, Anna Velia; Fazzi, Paola; Cordelli, Eugenia; Eleuteri, Patrizia; Leter, Giorgio; Spanò, Marcello

doi:10.1016/s0890-6238(02)00101-6

Cited by 57 publications

(25 citation statements)

References 53 publications

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“…The evaluation of chromatin integrity is important not only in human clinical and toxicological studies but also in species used in laboratory toxicological studies, such as small rodents (Traina et al 2003, Speit et al 2009), and to assess sperm quality in animals selected for assisted reproduction practice in zootechny (Rybar et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Sperm DNA fragmentation induced by DNAse I and hydrogen peroxide: an in vitro comparative study among different mammalian species

Villani

Eleuteri²,

Grollino³

et al. 2010

Reproduction

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Sperm DNA damage may have adverse effects on reproductive outcome. Sperm DNA breaks can be detected by several tests, which evaluate DNA integrity from different and complementary perspectives and offer a new class of biomarkers of the male reproductive function and of its possible impairment after environmental exposure. The remodeling of sperm chromatin produces an extremely condensed nuclear structure protecting the nuclear genome from adverse environments. This nuclear remodeling is species specific, and differences in chromatin structure may lead to a dissimilar DNA susceptibility to mutagens among species. In this study, the capacity of the comet assay in its two variants (alkaline and neutral) to detect DNA/chromatin integrity has been evaluated in human, mouse, and bull sperm. The hypothesis that chromatin packaging might influence the amount of induced and detectable DNA damage was tested by treating sperm in vitro with DNAse I, whose activity is strictly dependent upon its DNA accessibility. Furthermore, hydrogen peroxide (H 2 O 2 ) was used to assess whether spermatozoa of the three species showed a different sensitivity to oxidative stress. DNAse I-induced damage was also assessed by the sperm chromatin structure assay and the TUNEL assay, and the performances of these two assays were compared and correlated with the comet assay results. Results showed a different sensitivity to DNAse I treatment among the species with human sperm resulting the most susceptible. On the contrary, no major differences among species were observed after H 2 O 2 treatment. Furthermore, the three tests show a good correlation in revealing sperm with DNA strand breaks.

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Section: Introductionmentioning

confidence: 99%

Sperm DNA fragmentation induced by DNAse I and hydrogen peroxide: an in vitro comparative study among different mammalian species

Villani

Eleuteri²,

Grollino³

et al. 2010

Reproduction

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“…Male gonads have been found to be highly sensitive to orally administered LIN to adult rats: signifi cant reductions in the number of testicular spermatids and epididymal sperms have been described (Dalsenter et al, 1997a;Pages et al, 2002;Saradha and Mathur, 2006a). Similar eff ects were reported after prenatal or during lactation exposure to LIN of rats (Dalsenter et al, 1996(Dalsenter et al, , 1997b and mice (Traina et al, 2002), causing testicular alterations and increased chromatin abnormalities in epididymal sperm in male F1 mice (Traina et al, 2002), and a reduction in spermatogenesis, serum testosterone levels, testicular weight, spermatid and sperm counts (Dalsenter et al, 1997a). Although reproductive adverse eff ects associated with prenatal exposure to LIN seem to be of relevance in both genders, studies on the mechanism producing such an eff ect have been explored in females (Maranghi et al, 2007), whereas mechanistic information in males is scant.…”

Section: Introductionmentioning

confidence: 88%

“…Exposure to LIN produces several toxic eff ects, both in humans and in experimental animals (FAO/WHO, 2002;ATSDR, 2005), including impaired neurological (Parmar et al, 2003), immune (Meera et al, 1992) and developmental/reproductive function (Dalsenter et al, 1997a;Traina et al, 2002). Lindane is able to interact with several targets of the reproductive system in diff erent stages of the life cycle, including in the early embryonic period, during which LIN interferes with cell-to-cell communication (Scascitelli and Pacchierotti, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Following in utero exposure to LIN, alterations of reproductive structures and functions at sexual maturity have been described in females (Maranghi et al, 2007;Pages et al, 2002) and in males (Dalsenter et al, 1996(Dalsenter et al, , 1997aTraina et al, 2002). Male gonads have been found to be highly sensitive to orally administered LIN to adult rats: signifi cant reductions in the number of testicular spermatids and epididymal sperms have been described (Dalsenter et al, 1997a;Pages et al, 2002;Saradha and Mathur, 2006a).…”

Section: Introductionmentioning

confidence: 99%

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Effect of lindane on CYP‐mediated steroid hormone metabolism in male mice following in utero exposure

Consiglio

Angelis

Traina

et al. 2009

J of Applied Toxicology

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A wide number of pesticides, including highly persistent organochlorinated compounds, such as lindane (LIN), may induce reproductive and developmental alterations by directly binding to the estrogen/androgen receptors or altering steroid hormone metabolism. In the present work, we have investigated whether LIN in utero exposure of CD1 mice affects the reproductive system in male offspring by causing an impairment of the CYP-dependent steroid hormone metabolism. Dam exposure to 25 mg kg(-1) b.w. LIN occurred during critical developmental periods, from gestational days 9 to 16. Effects on hepatic CYP-mediated testosterone (TST) hydroxylase, aromatase activities and testicular parameters were tested at postnatal days (PND 50, 65-69, 100) that are critical for sexual maturation in CD1 mice. In the adult F1 mice significant changes of male reproductive endpoints (testis weight, spermatid number) as well as dramatic effects on CYP-mediated TST metabolism were observed on PND 65-69, in the absence of any of systemic toxicity. The levels of TST 6beta- and 2alpha-hydroxylation and dehydrogenation showed the highest level of reduction, suggesting CYP 3A and 2C families as the major target of LIN induced effects. All changes were almost recovered on PND 100. No effects on aromatase activity were evidenced. Overall, these findings provide useful information for a better characterization of the LIN mode of action. They suggest that LIN-induced toxicity in males is linked to an impairment of steroid hormone homeostasis, due to CYP-mediated TST catabolism modulation and differs from LIN receptor-mediated mechanism previously reported in females.

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“…Although the administration of DES in the neonatal period has been reported to induce impaired spermatogenesis (Sharpe et al, 1995(Sharpe et al, , 1998Atanassova et al, 1999Atanassova et al, , 2000Goyal et al, 2001Goyal et al, , 2003 and retarded development of the epididymis (Atanassova et al, 1999Mckinnell et al, 2001), there have been few reports on its effects of prenatal administration on these endpoints (Traina et al, 2003). In this study, we aimed to investigate in more detail the effects of the prenatal administration of different low doses of DES on the reproductive system by examining the sexual differentiation of the central nervous system, the functions of the pituitary gland, and sex hormone levels, spermatogenesis, and epididymal development in mature male rats.…”

Section: Introductionmentioning

confidence: 99%

Effects of Maternal Exposure to a Low Dose of Diethylstilbestrol on Sexual Dimorphic Nucleus Volume and Male Reproductive System in Rat Offspring

Yamamoto¹,

Shirai²,

Tamura³

et al. 2005

J. Toxicol. Sci.

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-Diethylstilbestrol (DES) was administered subcutaneously at 0.5, 1.5 or 4.5 µg/kg/day (DES 0.5, 1.5 and 4.5 groups, respectively) to pregnant SD rats daily on days 7-21 of gestation, to investigate its effects on the development and functions of the reproductive system in their male offspring. Of the 10 pregnant rats in the DES 4.5 group, only 1 delivered, and this rat could not suckle the pups. Rat pups in the DES 0.5 and 1.5 groups were autopsied at 1, 3, 6 and 15 weeks after birth. The testosterone concentrations in the DES 1.5 and 0.5 groups at 6 weeks were significantly decreased and the plasma LH concentrations were not altered. In the DES 1.5 group, DES treatment did not change the volume of the sexually dimorphic nucleus in the preoptic area (SDN-POA) in the male offspring, although this dose of DES increased the volume of SDN-POA in female offspring. The DES treatment altered frequencies in the cycles of the seminiferous tubules, and suppressed histological maturation in the epididymis and the prostate weight. These observations indicate that prenatally administered DES impairs testicular endocrine function continuously as well as putuitary function, but the induced low level of testosterone disrupts spermatogensis and permanently inhibits the morphological development of epididymis and prostate.

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Long-lasting effects of lindane on mouse spermatogenesis induced by in utero exposure

Cited by 57 publications

References 53 publications

Sperm DNA fragmentation induced by DNAse I and hydrogen peroxide: an in vitro comparative study among different mammalian species

Sperm DNA fragmentation induced by DNAse I and hydrogen peroxide: an in vitro comparative study among different mammalian species

Effect of lindane on CYP‐mediated steroid hormone metabolism in male mice following in utero exposure

Effects of Maternal Exposure to a Low Dose of Diethylstilbestrol on Sexual Dimorphic Nucleus Volume and Male Reproductive System in Rat Offspring

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