Reproductive abnormalities in adult male mice following preimplantation exposures to estradiol or pesticide methoxychlor

Amstislavsky, S. Ya.; Amstislavskaya, Tamara G.; Amstislavsky, Vjacheslav S.; Tibeikina, M. A.; Осипов, К. В.; Eroschenko, Victor P.

doi:10.1016/j.reprotox.2005.07.009

Cited by 18 publications

(19 citation statements)

References 27 publications

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“…MXC and its major metabolites, mono-desmethyl-MXC (OH-MXC) and bisdesmethyl-MXC (HPTE), possess ERα agonist, ERβ antagonist and antiandrogenic activities [12], [13], [14]. Perinatal exposure to high-dose MXC is able to cause many reproductive abnormalities in adult male mice or rat [15], [16], [17], [18], [19], [20], [21]. Amstislavsky et al reported that transient exposure to 166.7 mg/kg/d MXC at embryonic day (E) 2 to E4 significantly increased the seminal vesicles weight and decreased the testosterone (T) level in male mice at 6 months [15].…”

Section: Introductionmentioning

confidence: 99%

Perinatal Exposure to Low-Dose Methoxychlor Impairs Testicular Development in C57BL/6 Mice

Zhang

Liu

et al. 2014

PLoS ONE

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Methoxychlor (MXC), an organochlorine pesticide, has adverse effects on male reproduction at toxicological doses. Humans and wild animals are exposed to MXC mostly through contaminated dietary intake. Higher concentrations of MXC have been found in human milk, raising the demand for the risk assessment of offspring after maternal exposure to low doses of MXC. In this study, pregnant mice (F0) were given intraperitoneal daily evening injections of 1 mg/kg/d MXC during their gestational (embryonic day 0.5, E0.5) and lactational periods (postnatal day 21.5, P21.5), and the F1 males were assessed. F1 testes were collected at P0.5, P21.5 and P45.5. Maternal exposure to MXC disturbed the testicular development. Serum testosterone levels decreased, whereas estradiol levels increased. To understand the molecular mechanisms of exposure to MXC in male reproduction, the F1 testes were examined for changes in the expression of steroidogenesis- and spermatogenesis- related genes. RT-PCR analysis demonstrated that MXC significantly decreased Cyp11a1 and increased Cyp19a1; furthermore, it downregulated certain spermatogenic genes (Dazl, Boll, Rarg, Stra8 and Cyclin-a1). In summary, perinatal exposure to low-dose MXC disturbs the testicular development in mice. This animal study of exposure to low-dose MXC in F1 males suggests similar dysfunctional effects on male reproduction in humans.

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Section: Introductionmentioning

confidence: 99%

Perinatal Exposure to Low-Dose Methoxychlor Impairs Testicular Development in C57BL/6 Mice

Zhang

Liu

et al. 2014

PLoS ONE

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“…MXC was also found to induce a decrease in the ovarian estrogen receptor b (ESR2) expression (Armenti et al 2008). In male rodents, MXC induced a decrease in sexual arousal (Eroschenko et al 2002), an increase in sexual maturation (Amstislavsky et al 2004), a decrease in the circulating testosterone level (Amstislavsky et al 2006), and decreases in testis weight, Sertoli cell number, and spermatogenesis potential (Staub et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Specific transgenerational imprinting effects of the endocrine disruptor methoxychlor on male gametes

2011

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Endocrine-disrupting chemicals (EDCs), among which methoxychlor (MXC), have been reported to affect the male reproductive system. This study evaluates the possible deleterious effects of MXC on imprinted genes. After administration of the chemical in adult male mice or in pregnant mice we analyzed by pyrosequencing possible methylation defects in two paternally imprinted (H19 and Meg3 (Gtl2)) and three maternally imprinted (Mest (Peg1), Snrpn, and Peg3) genes in the sperm and in the tail, liver, and skeletal muscle DNAs of the adult male mice and of the male offspring. MXC treatment of adult mice decreased the percentages of methylated CpGs of Meg3 and increased those of Mest, Snrpn, and Peg3 in the sperm DNA. MXC treatment of pregnant mice decreased the mean sperm concentrations by 30% and altered the methylation pattern of all the imprinted genes tested in the F1 offspring. In the latter case, MXC effects were transgenerational but disappeared gradually from F1 to F3. MXC did not affect imprinting in the somatic cells, suggesting that it exerts its damaging effects via the process of reprogramming that is unique to gamete development. A systematic analysis at the CpG level showed a heterogeneity in the CpG sensitivity to MXC. This observation suggests that not only DNA methylation but also other epigenetic modifications can explain the transgenerational effects of MXC. The reported effects of EDCs on human male spermatogenesis might be mediated by complex imprinting alterations analogous to those described in this study.

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“…However, in a study in which even lower doses of vinclozolin were given to pregnant rats (3.125 and 6.25 mg/kg/day), subtle alterations in the differentiation of the external genitalia, ventral prostate, and nipple tissue in male offspring were observed. This is an order of magnitude below previously reported developmental no observed effect levels ( NOELs , 22 -77 mg/kg/day; Amstislavsky et al , 2006 ). Thus, it has been proposed that the anti -androgenic effects of vinclozolin can be produced at very low levels, and studies that do not include androgen -sensitive end points might yield NOELs that are at least an order of magnitude too high.…”

Section: Fungicidesmentioning

confidence: 67%

“…In another in vitro study, HPTE inhibited LH -stimulated testosterone production in cultured Leydig cells from immature rats and the estrogen receptor antagonist ICI 182,780 reversed this inhibition (Akingbemi et al , 2000 ). Long -term effects in male offspring were seen following transplacental exposure to MXC (Amstislavsky et al , 2006 ). At six months of age, testosterone levels were reduced, seminal vesicle weight was increased, and sexual arousal was compromised in males exposed in utero to MXC.…”

Section: Agricultural Compoundsmentioning

confidence: 96%

Mechanisms of Reproductive Toxicity

Keating¹,

Hoyer²

2008

Drug Metabolism Handbook

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Reproductive abnormalities in adult male mice following preimplantation exposures to estradiol or pesticide methoxychlor

Cited by 18 publications

References 27 publications

Perinatal Exposure to Low-Dose Methoxychlor Impairs Testicular Development in C57BL/6 Mice

Perinatal Exposure to Low-Dose Methoxychlor Impairs Testicular Development in C57BL/6 Mice

Specific transgenerational imprinting effects of the endocrine disruptor methoxychlor on male gametes

Mechanisms of Reproductive Toxicity

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