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RESEARCH ARTICLE
Contents Vol 19(4)

Effects of aroclor 1254 on the expression of the KAP3 gene and reproductive function in rats

Chae Kwan Lee A , Han Seung Kang B , Ju Ran Kim C , Byung Ju Lee D , Jong Tae Lee A , Jeong Ho Kim A , Dae Hwan Kim A , Chang Hee Lee A , Jin Hong Ahn A , Chae Un Lee A , Seong Jin Yu C and Sung Goo Kang C E
+ Author Affiliations
- Author Affiliations

A Institute of Industrial Medicine, Department of Occupational and Environmental Medicine, Busan Paik Hospital, Inje University, Busan 614-735, South Korea.

B Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, South Korea.

C School of Biotechnology and Biomedical Sciences, Inje University, Kimhae 621-749, South Korea.

D Department of Biological Sciences, College of Natural Sciences, Ulsan University, Ulsan 680-749, South Korea.

E Corresponding author. Email: biosgkan@inje.ac.kr

Reproduction, Fertility and Development 19(4) 539-547 https://doi.org/10.1071/RD06117
Submitted: 8 September 2006  Accepted: 6 March 2007   Published: 3 May 2007

Abstract

The present study investigated the effects of aroclor 1254 (A1254) on the expression of the kinesin superfamily associated protein 3 (KAP3) gene in F1 rat brain during brain sexual differentiation and puberty. In addition, the effects of A1254 on reproductive function were examined. The KAP3 gene is involved in the neurogenesis and synaptogenesis of sexual differentiation in rats and also during puberty. In the present study, pregnant Sprague–Dawley rats each received a daily dose of A1254 (0, 10, 50 mg kg–1) dissolved in 1.0 mL corn oil by gavage, from gestational Day (GD) 8 to postnatal Day (PD) 21. The mRNA levels of the KAP3 gene in hypothalamic tissues were analysed by northern blot hybridisation during the critical periods of brain sexual differentiation (GD18 and PD5) and puberty (PD28). Variables affecting reproduction in F1 female rats, such as vaginal opening (VO), vaginal oestrus (VE) and oestrous cyclicity, were recorded. Depending on the sex and A1254 exposure (control or 50 mg kg–1 day–1), F1 rats were divided into three mating groups, namely control male–control female, control male–A1254-treated female and A1254-treated male–control female. During the critical periods of brain sexual differentiation (GD18, PD5) and puberty (PD28), KAP3 mRNA levels were significantly reduced in A1254-treated fetal and pubertal rat brains relative to those of control groups. In A1254-treated F1 female rats, VO and VE were delayed, the percentage of irregular oestrous cycles was increased and the duration of the oestrous cycle was extended in a dose-dependent manner compared with control groups. Treatment with a high dose of A1254 significantly impaired the reproductive function of both male and female F1 rats, including mating and pregnancy indices and the number of live fetuses. These data suggest that A1254 disrupts transcriptional regulation of the KAP3 gene in fetal and pubertal rat brains and that these effects may be related to A1254-induced abnormal brain sexual differentiation and lowered reproductive function in F1 rats.

Additional keywords: fetoneonatal oestrogen-binding protein, kinesin superfamily protein, oestrogen, testosterone.


Acknowledgement

This work was supported, in part, by Inje University Research Fund (2004).


References

Arnold, D. L. , Bryce, F. R. , Clegg, D. J. , Cherry, W. , Tanner, J. R. , and Hayward, S. (2000). Dosing via gavage or diet for reproduction studies: a pilot study using two fat-soluble compounds – hexachlorobenzene and aroclor 1254. Food Chem. Toxicol. 38, 697–706.
| Crossref | GoogleScholarGoogle Scholar | PubMed | Everett J. W. 1989. ‘Neurobiology of Reproduction in the Female Rat: A 50-year Perspective.’ (Springer: New York.)

Faber, K. A. , and Hughes, C. L. (1991). The effect of neonatal exposure to DES, genistein, and zearalenone on pituitary responsiveness and SDN–POA volume in the castrated adult rat. Biol. Reprod. 45, 649–653.
| Crossref | GoogleScholarGoogle Scholar | PubMed | Feder H. H. 1981. Estrous cyclicity in mammals. In ‘Neuroendocrinology of Reproduction: Physiology and Behavior’. (Ed. N. T. Adler.) pp. 279–290. (Plenum Press: New York.)

Frame, G. (1999). Improved producer for signal DB-XLM column GC-MS-SIM quantitation of PCB congener distributions and characterization of two different preparations sold as ‘aroclor 1254’. J. High Resolut. Chromatogr. 22, 533–540.
| Crossref | GoogleScholarGoogle Scholar |

Gallant, T. L. , Singh, A. , and Chu, I. (2000). PCB 118 induces ultra structural alterations in the rat liver. Toxicology 145, 127–134.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Gilbert, M. E. (2003). Perinatal exposure to polychlorinated biphenyls alters excitatory synaptic transmission and short-term plasticity in the hippocampus of the adult rat. Neurotoxicology 24, 851–860.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Gore, A. C. , Wu, T. J. , Oung, T. , Lee, J. B. , and Woller, M. J. A. (2002). Novel mechanism for endocrine-disrupting effects of polychlorinated biphenyls: direct effects on gonadotropin-releasing hormone neurones. J. Neuroendocrinol. 14, 814–823.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Gorski, R. A. , Gordon, J. H. , Shryne, J. E. , and Southam, A. M. (1978). Evidence for a morphological sex difference within the medial preoptic area of the rat brain. Brain Res. 148, 333–346.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Handa, R. J. , Corbier, P. , Shryne, J. E. , Schoonmaker, J. N. , and Gorski, R. A. (1985). Differential effects of the perinatal steroid environment on three sexually dimorphic parameters of the rat brain. Biol. Reprod. 32, 855–864.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Hany, J. , Lilienthal, H. , Sarasin, A. , Roth-Harer, A. , Fastabend, A. , Dunemann, L. , Lichtensteiger, W. , and Winneke, G. (1999). Developmental exposure of rats to a reconstituted PCB mixture or aroclor 1254: effects on organ weights, aromatase activity, sex hormone levels, and sweet preference behavior. Toxicol. Appl. Pharmacol. 158, 231–243.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Hayashi, S. , and Aihara, M. (1989). Neonatal estrogenization of the female rat: a useful model for analysis of hypothalamic involvement of gonadotropin release. Zoolog. Sci. 6, 1059–1068.


Hirokawa, N. (1997). The mechanisms of fast and slow transport in neurons: identification and characterization of the new kinesin superfamily motors. Curr. Opin. Neurobiol. 7, 605–614.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Hirokawa, N. , Sato-Yoshitake, R. , Kobayashi, N. , Pfister, K. K. , Bloom, G. S. , and Brady, S. T. (1991). Kinesin associates with anterogradely transported membranous organelles in vivo. J. Cell Biol. 114, 295–302.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Hutchison, J. B. , Wozniak, A. , Beyer, C. , and Hutchison, R. E. (1996). Regulation of sex-specific formation of oestrogen in brain development: endogenous inhibition of aromatase. J. Steroid Biochem. Mol. Biol. 56, 201–207.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Jacobson, C. D. , Csernus, V. J. , Shryne, J. E. , and Gorski, R. A. (1981). The influence of gonadectomy, androgen exposure, or a gonadal graft in the neonatal rat on the volume of the sexually dimorphic nucleus of the preoptic area. J. Neurosci. 1, 1142–1147.
| PubMed |

Kaya, H. , Hany, J. , Fastabend, A. , Roth-Harer, A. , Winneke, G. , and Lilienthal, H. (2002). Effects of maternal exposure to a reconstituted mixture of polychlorinated biphenyls on sex-dependent behaviors and steroid hormone concentrations in rats: dose–response relationship. Toxicol. Appl. Pharmacol. 178, 71–81.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Kester, M. H. , Bulduk, S. , Tibboel, D. , Meinl, W. , and Glatt, H. , et al. (2000). Potent inhibition of estrogen sulfotransferase by hydroxylated PCB metabolites: a novel pathway explaining the estrogenic activity of PCBs. Endocrinology 141, 1897–1900.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Kim, H. , Ha, C. M. , Choi, J. , Choi, E. J. , Jeon, J. , Kim, C. , Park, S. K. , Kang, S. S. , Kim, K. , and Lee, B. J. (2002). Ontogeny and the possible function of a novel epidermal growth factor-like repeat domain-containing protein, NELL2, in the rat brain. J. Neurochem. 83, 1389–1400.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Kodavanti, P. R. , and Ward, T. R. (2005). Differential effects of commercial polybrominated diphenyl ether and polychlorinated biphenyl mixtures on intracellular signaling in rat brain in vitro. Toxicol. Sci. 85, 952–962.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Kodavanti, P. R. , Kannan, N. , Yamashita, N. , Derr-Yellin, E. C. , Ward, T. R. , Burgin, D. E. , Tilson, H. A. , and Birnbaum, L. S. (2001). Differential effects of two lots of aroclor 1254: congener-specific analysis and neurochemical end points. Environ. Health Perspect. 109, 1153–1161.
| PubMed |

Kuroda, S. , and Tanizawa, K. (1999). Involvement of epidermal growth factor-like domain of NELL proteins in the novel protein–protein interaction with protein kinase C. Biochem. Biophys. Res. Commun. 265, 752–757.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Kuroda, S. , Oyasu, M. , Kawakami, M. , Kanayama, N. , Tanizawa, K. , Saito, N. , Abe, T. , Matsuhashi, S. , and Ting, K. (1999). Biochemical characterization and expression analysis of neural thrombospondin-1-like proteins NELL1 and NELL2. Biochem. Biophys. Res. Commun. 265, 79–86.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Lazzaro, D. , Price, M. , de Felice, M. , and Di Lauro, R. (1991). The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain. Development 113, 1093–1104.
| PubMed |

Lee, B. J. , Cho, G. J. , Norgren, R. B. , Junier, M. P. , Hill, D. F. , Tapia, V. , Costa, M. E. , and Ojeda, S. R. (2001). TTF-1, a homeodomain gene required for diencephalic morphogenesis, is postnatally expressed in the neuroendocrine brain in a developmentally regulated and cell-specific fashion. Mol. Cell. Neurosci. 17, 107–126.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

McEwen, B. S. , Jones, K. J. , and Pfaff, D. W. (1987). Hormonal control of sexual behavior in the female rat: molecular, cellular and neurochemical studies. Biol. Reprod. 36, 37–45.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Mariussen, E. , and Fonnum, F. (2001). The effect of polychlorinated biphenyls on the high affinity uptake of the neurotransmitters, dopamine, serotonin, glutamate and GABA, into rat brain synaptosomes. Toxicology 159, 11–21.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Moore, M. , Mustain, M. , David, K. , Chen, I. , Safe, S. , Zacharrewski, T. , Gillesby, B. , Joyeuk, A. , and Balaguer, P. (1997). Antiestrogenic activity of hydroxylated polychlorinated bisphenol congeners identified in human serum. Toxicol. Appl. Pharmacol. 142, 160–168.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Morse, D. C. , Plug, A. , Wesseling, W. , van den Berg, K. J. , and Brouwer, A. (1996). Persistent alterations in regional brain glial filbrillary acidic protein and synaptophysin levels following pre- and postnatal polychlorinated biphenyl exposure. Toxicol. Appl. Pharmacol. 139, 252–261.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Naftolin, F. , Garcia-Segura, L. M. , Keefe, D. , Leranth, C. , Maclusky, N. J. , and Brawer, J. R. (1990). Estrogen effects on the synaptology and neural membranes of the rat hypothalamic arcuate nucleus. Biol. Reprod. 42, 21–28.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Parsons, B. , MacLusky, N. J. , Krey, L. , Pfaff, D. W. , and McEwen, B. S. (1980). The temporal relationship between estrogen-inducible progestin receptors in the female rat brain and the time course of estrogen activation of mating behavior. Endocrinology 107, 774–779.
| PubMed |

Pinilla, L. , Trimino, E. , and Garnelo, P. (1993). Changes in pituitary secretion during the early postnatal period and anovulatory syndrome induced by neonatal oestrogen or androgen in rats. J. Reprod. Fertil. 97, 13–20.
| PubMed |

Price, M. , Lazzaro, D. , Pohl, T. , Mattei, M. G. , Ruther, U. , Olivo, J. C. , Duboule, D. , and Di Lauro, R. (1992). Regional expression of the homeobox gene Nkx-2.2 in the developing mammalian forebrain. Neuron 8, 241–255.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Rhees, R. W. , Shryne, J. E. , and Gorski, R. A. (1990). Termination of the hormone-sensitive period for differentiation of the sexually dimorphic nucleus of the preoptic area in male and female rats. Brain Res. Dev. Brain Res. 52, 17–23.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Roegge, C. S. , Seo, B. W. , Crofton, K. M. , and Schantz, S. L. (2000). Gestational–lactational exposure to aroclor 1254 impairs radial-arm maze performance in male rats. Toxicol. Sci. 57, 121–130.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Safe, S. H. (1994). Polychlorinated biphenyls (PCBs): environmental impact, biochemical and toxic response, and implication for risk assessment. Crit. Rev. Toxicol. 24, 87–149.
| PubMed |

Sager, D. B. (1983). Effects of postnatal exposure to polychlorinated bisphenol on adult male reproductive function. Environ. Res. 31, 76–94.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Sager, D. B. , and Girard, D. M. (1994). Long-term effects on reproductive parameters in female rats after translactational exposure to PCBs. Environ. Res. 66, 52–76.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Seegal, R. F. (1996). Epidermiological and laboratory evidence of PCB-induced neurotoxicity. Crit. Rev. Toxicol. 26, 709–739.
| PubMed |

Seiler, P. , Fischer, B. , Lindenau, A. , and Beier, H. M. (1994). Effects of persistent chlorinated hydrocarbons on fertility and embryonic development in the rabbit. Hum. Reprod. 9, 1920–1926.
| PubMed |

Simerly, R. B. , Zee, M. C. , Pendleton, J. W. , Lubahn, D. B. , and Korach, K. S. (1997). Estrogen receptor-dependent sexual differentiation of dopaminergic neurons in the preoptic region of the mouse. Proc. Natl Acad. Sci. USA 94, 14 077–14 082.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Stewart, P. , Reihman, J. , Lonky, E. , Darvill, T. , and Pagona, J. (2000). Prenatal PCB exposure and neonatal behavioral assessment scale (NBAS) performance. Neurotoxicol. Teratol. 22, 21–29.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Toran-Aller, C. D. (1984). Gonadal hormones and brain development: implications for the genesis of sexual differentiation. Ann. N.Y. Acad. Sci. 435, 101–111.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Tyl, R. W. , Marr, M. C. , Myers, C. B. , Ross, W. P. , and Friedman, M. A. (2000). Relationship between acrylamide reproductive and neurotoxicity an male rats. Reprod. Toxicol. 14, 147–157.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

von Saal, F. S. , and Bronson, F. H. (1980). Sexual characteristics of adult female mice are correlated with their blood testosterone levels during prenatal development. Science 208, 597–599.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Wang, X. Q. , Fang, J. , Nunez, A. A. , and Clemens, L. G. (2002). Developmental exposure to polychlorinated biphenyls affects sexual behavior of rats. Physiol. Behav. 75, 689–696.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Webb, R. G. , and McCall, A. C. (1972). Industrial chemicals: identities of polychlorinated biphenyl isomers in aroclors. J. Assoc. Off. Anal. Chem. 55, 746–752.
| PubMed |

Weisz, J. , and Ward, I. L. (1980). Plasma testosterone and progesterone titers of pregnant rats, their male and female fetuses, and neonatal offspring. Endocrinology 106, 306–316.
| PubMed |

Yamada, T. , Hara, M. , Ohba, Y. , Inoue, T. , and Ohno, H. (1985). Studies on implantation traces in rats. II. Staining of cleared uteri, formation and distribution of implantation treces. Exp. Anim. 34, 249–260.


Yamazaki, H. , Nakata, T. , Okada, Y. , and Hirokawa, N. (1995). KIF3A/B: A heterodimeric kinesin superfamily protein that works as a microtuble plus end-directed motor for membrane organelle transport. J. Cell Biol. 130, 1387–1399.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Yamazaki, H. , Nakata, T. , Okada, Y. , and Hirokawa, N. (1996). Cloning and characterization of KAP3: a novel kinesin superfamily-associated protein of KIF3A/3B. Proc. Natl Acad. Sci. USA 93, 8443–8448.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Yang, J. H. , Derr-Yellin, E. C. , and Kodavanti, P. R. (2003). Alterations in brain protein kinase C isoforms following developmental exposure to a polychlorinated biphenyl mixture. Brain Res. Mol. Brain Res. 111, 123–135.
| Crossref | GoogleScholarGoogle Scholar | PubMed |