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Title: Methyl parathion inhibits the nuclear maturation, decreases the cytoplasmic quality in oocytes and alters the developmental potential of embryos of Swiss albino mice

Abstract

Methyl parathion (MP) is one of the most commonly used and extremely toxic organophosphorous group of pesticide. A large number of studies in the literature suggest that it has adverse effects on the male reproductive system. However, there is limited information about its toxicity to the female reproductive system. In the present study we report the toxic effects of methyl parathion on the female reproductive system using Swiss albino mice as the experimental model. The female mice were administered orally with 5, 10 and 20 mg/kg of MP. One week later, the mice were superovulated with pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) to study the quality of the oocytes, spindle organization, developmental potential of early embryos and the DNA integrity in blastocysts. MP exposure resulted in a non-significant decrease in the number of primordial follicles and increased DNA damage in granulosa cells. Though MP did not have any effect on the ovulation it had a significant inhibitory effect on the nuclear maturity of oocytes which was associated with spindle deformity. In addition, the oocytes had higher cytoplasmic abnormalities with depleted glutathione level. Even though it did not have any effect on the fertilization and blastocyst ratemore » at lower doses, at 20 mg/kg MP it resulted in a significant decrease in blastocyst hatching, decrease in cell number and high DNA damage. While low body weight gain was observed in F1 generation from 5 mg/kg group, at higher dose, the body weight in F1 generation was marginally higher than control. Post-natal death in F1 generation was observed only in mice treated with 20 mg/kg MP. In conclusion, we report that MP has adverse effects on the oocyte quality, developmental potential of the embryo and reproductive outcome. - Highlights: • Methyl parathion induces severe cytoplasmic abnormalities in oocytes. • Inhibits nuclear maturation and spindle damage • Poor blastocyst quality and high DNA damage.« less

Authors:
; ;  [1]; ;  [2]; ;  [3];  [1];  [1]
  1. Division of Clinical Embryology, Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal University, Manipal 576 104 (India)
  2. Department of Anatomy, Kasturba Medical College, Manipal University, Manipal 576 104 (India)
  3. Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576 104 (India)
Publication Date:
OSTI Identifier:
22439832
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 279; Journal Issue: 3; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; DAMAGE; DNA; DNA DAMAGES; DOSES; EMBRYOS; FERTILIZATION; GLUTATHIONE; HATCHING; HCG; MICE; MITOCHONDRIA; OOCYTES; OVULATION; PARATHION; TOXICITY

Citation Formats

Nair, Ramya, Singh, Vikram Jeet, Salian, Sujith Raj, Kalthur, Sneha Guruprasad, D'Souza, Antony Sylvan, Shetty, Pallavi K., Mutalik, Srinivas, Kalthur, Guruprasad, E-mail: guru.kalthur@manipal.edu, and Adiga, Satish Kumar. Methyl parathion inhibits the nuclear maturation, decreases the cytoplasmic quality in oocytes and alters the developmental potential of embryos of Swiss albino mice. United States: N. p., 2014. Web. doi:10.1016/J.TAAP.2014.07.004.
Nair, Ramya, Singh, Vikram Jeet, Salian, Sujith Raj, Kalthur, Sneha Guruprasad, D'Souza, Antony Sylvan, Shetty, Pallavi K., Mutalik, Srinivas, Kalthur, Guruprasad, E-mail: guru.kalthur@manipal.edu, & Adiga, Satish Kumar. Methyl parathion inhibits the nuclear maturation, decreases the cytoplasmic quality in oocytes and alters the developmental potential of embryos of Swiss albino mice. United States. doi:10.1016/J.TAAP.2014.07.004.
Nair, Ramya, Singh, Vikram Jeet, Salian, Sujith Raj, Kalthur, Sneha Guruprasad, D'Souza, Antony Sylvan, Shetty, Pallavi K., Mutalik, Srinivas, Kalthur, Guruprasad, E-mail: guru.kalthur@manipal.edu, and Adiga, Satish Kumar. Mon . "Methyl parathion inhibits the nuclear maturation, decreases the cytoplasmic quality in oocytes and alters the developmental potential of embryos of Swiss albino mice". United States. doi:10.1016/J.TAAP.2014.07.004.
@article{osti_22439832,
title = {Methyl parathion inhibits the nuclear maturation, decreases the cytoplasmic quality in oocytes and alters the developmental potential of embryos of Swiss albino mice},
author = {Nair, Ramya and Singh, Vikram Jeet and Salian, Sujith Raj and Kalthur, Sneha Guruprasad and D'Souza, Antony Sylvan and Shetty, Pallavi K. and Mutalik, Srinivas and Kalthur, Guruprasad, E-mail: guru.kalthur@manipal.edu and Adiga, Satish Kumar},
abstractNote = {Methyl parathion (MP) is one of the most commonly used and extremely toxic organophosphorous group of pesticide. A large number of studies in the literature suggest that it has adverse effects on the male reproductive system. However, there is limited information about its toxicity to the female reproductive system. In the present study we report the toxic effects of methyl parathion on the female reproductive system using Swiss albino mice as the experimental model. The female mice were administered orally with 5, 10 and 20 mg/kg of MP. One week later, the mice were superovulated with pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) to study the quality of the oocytes, spindle organization, developmental potential of early embryos and the DNA integrity in blastocysts. MP exposure resulted in a non-significant decrease in the number of primordial follicles and increased DNA damage in granulosa cells. Though MP did not have any effect on the ovulation it had a significant inhibitory effect on the nuclear maturity of oocytes which was associated with spindle deformity. In addition, the oocytes had higher cytoplasmic abnormalities with depleted glutathione level. Even though it did not have any effect on the fertilization and blastocyst rate at lower doses, at 20 mg/kg MP it resulted in a significant decrease in blastocyst hatching, decrease in cell number and high DNA damage. While low body weight gain was observed in F1 generation from 5 mg/kg group, at higher dose, the body weight in F1 generation was marginally higher than control. Post-natal death in F1 generation was observed only in mice treated with 20 mg/kg MP. In conclusion, we report that MP has adverse effects on the oocyte quality, developmental potential of the embryo and reproductive outcome. - Highlights: • Methyl parathion induces severe cytoplasmic abnormalities in oocytes. • Inhibits nuclear maturation and spindle damage • Poor blastocyst quality and high DNA damage.},
doi = {10.1016/J.TAAP.2014.07.004},
journal = {Toxicology and Applied Pharmacology},
number = 3,
volume = 279,
place = {United States},
year = {Mon Sep 15 00:00:00 EDT 2014},
month = {Mon Sep 15 00:00:00 EDT 2014}
}
  • Paternal germline exposure to organophosphorous pesticides (OP) has been associated with reproductive failures and adverse effects in the offspring. Methyl parathion (Me-Pa), a worldwide-used OP, has reproductive adverse effects and is genotoxic to sperm. Oxidative damage has been involved in the genotoxic and reproductive effects of OP. The purpose of this study was to determine the effects of Me-Pa on spermatozoa function and ability to fertilize. Male mice were exposed to Me-Pa (20 mg/kg bw, i.p.) and spermatozoa from epididymis-vas deferens were collected at 7 or 28 days post-treatment (dpt) to assess the effects on maturing spermatozoa and spermatocytes, respectively.more » DNA damage was evaluated by nick translation (NT-positive cells) and SCSA (percentDFI); lipoperoxidation (LPO) by malondialdehyde production; sperm function by spontaneous- and induced-acrosome reactions (AR); mitochondrial membrane potential (MMP) by using the JC-1 flurochrome; and, fertilization ability by an in vitro assay and in vivo mating. Results showed alterations in DNA integrity (percentDFI and NT-positive cells) at 7 and 28 dpt, in addition to decreased sperm quality and a decrease in induced-AR; reduced MMP and LPO was observed only at 7 dpt. We found negative correlations between LPO and all sperm alterations. Altered sperm functional parameters were associated with reduced fertilization rates at both times, evaluated either in vitro or in vivo. These results show that Me-Pa exposure of maturing spermatozoa and spermatocytes affects many sperm functional parameters that result in a decreased fertilizing capacity. Oxidative stress seems to be a likely mechanism ofthe detrimental effects of Me-Pa in male germ cells.« less
  • To gain insight into the mechanisms involved in the formation of maternally stored mRNPs during Xenopus laevis development, we searched for soluble cytoplasmic proteins of the oocyte that are able to selectively bind mRNAs, using as substrate radiolabeled mRNA. In vitro mRNP assembly in solution was followed by UV-cross-linking and RNase digestion, resulting in covalent tagging of polypeptides by nucleotide transfer. Five polypeptides of approximately 54, 56 60, 70, and 100 kD (p54, p56, p60, p70, and p100) have been found to selectively bind mRNA and assemble into mRNPs. These polypeptides, which correspond to previously described native mRNP components, occurmore » in three different particle classes of approximately 4.5S, approximately 6S, and approximately 15S, as also determined by their reactions with antibodies against p54 and p56. Whereas the approximately 4.5S class contains p42, p60, and p70, probably each in the form of individual molecules or small complexes, the approximately 6S particles appears to consist only of p54 and p56, which occur in a near-stoichiometric ratio suggestive of a heterodimer complex. The approximately 15S particles contain, in addition to p54 and p56, p60 and p100 and this is the single occurring form of RNA-binding p100. We have also observed changes in the in vitro mRNA binding properties of these polypeptides during oogenesis and early embryonic development, in relation to their phosphorylation state and to the activity of an approximately 15S particle-associated protein kinase, suggesting that these proteins are involved in the developmental translational regulation of maternal mRNAs.« less
  • G proteins, which in many somatic cells serve as mediators of signal transduction, were identified in preimplantation mouse embryos by their capacity to undergo pertussis toxin-catalyzed ADP-ribosylation. Two pertussis toxin (PT) substrates with Mr = 38,000 and 39,000 (alpha 38 and alpha 39) are present in approximately equal amounts. Relative to the amount in freshly isolated germinal vesicle (GV)-intact oocytes, the amount of PT-catalyzed ADP-ribosylation of alpha 38-39 falls during oocyte maturation, rises between the one- and two-cell stages, falls by the eight-cell and morula stages, and increases again by the blastocyst stage. The decrease in PT-catalyzed ADP-ribosylation of alphamore » 38-39 that occurs during oocyte maturation, however, does not require germinal vesicle breakdown (GVBD), since inhibiting GVBD with 3-isobutyl-1-methyl xanthine (IBMX) does not prevent the decrease in the extent of PT-catalyzed ADP-ribosylation. A biologically active phorbol diester (12-O-tetradecanoyl phorbol 13-acetate), but not an inactive one (4 alpha-phorbol 12,13-didecanoate, 4 alpha-PDD), totally inhibits the increase in PT-catalyzed ADP-ribosylation of alpha 38-39 that occurs between the one- and two-cell stage; TPA inhibits cleavage, but not transcriptional activation, which occurs in the two-cell embryo. In contrast, cytochalasin D, genistein, or aphidicolin, each of which inhibits cleavage of one-cell embryos, or alpha-amanitin or H8, each of which inhibits transcriptional activation but not cleavage of one-cell embryos, have little or inhibitory effects on the increase in PT-catalyzed ADP-ribosylation of alpha 38-39. Results of immunoblotting experiments using an antibody that is highly specific for alpha il-3 reveal the presence of a cross-reactive species of Mr = 38,000 (alpha 38) in the GV-intact oocyte, metaphase II-arrested egg, and one-, two-cell embryos.« less