IN UTERO AND LACTATIONAL EXPOSURE TO DIOXIN ALTERED THE REPRODUCTIVE FUNCTION IN FEMALE RAT OFFSPRING BEFORE AND AFTER PUBERTY التعرض إلى الديوکسين عن طريق الرحم و الرضاعة يغير الوظيفة الإنجابية في ذرية الفئران الإناث قبل وبعد سن البلوغ | ||
| Assiut University Bulletin for Environmental Researches | ||
| Article 2, Volume 16.1, Issue 16.1, March 2013, Pages 13-39 PDF (2.15 M) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/auber.2013.148457 | ||
| Abstract | ||
| ABSTRACT: To evaluate effects of in utero and lactational 2,3,7,8-tetrachlorodibenzo-rho-dioxin (TCDD) exposure on the reproductive functionin female rat offspring, before and after puberty. The pregnant Sprague Dawely rat administered 0, or 1.0 mg TCDD/kg on Gestation Day (GD) 8 and 15. Female offspring were examined at the post-weanling before puberty on posnatal day (PND) 21 and in young adult stage of development on PND42. Ovulation assessment, radioimmunoassay for serum gonadotropins, steroids and histo-morphmetric analysis to the ovaries were evaluated. The analysis included a count, measurement and classification of preantral and antral follicles throughout the entire ovary on PND 21. The results indicate that TCDD treatment significantly reduced the ovulation rate, serum gonadotropins, steroids levels and the number of antral and preantral follicles of certain size classes. The histopathological examination revealed small preovulatory follicles displaying an atretic morphologic difference among the ovaries of rats exposed to TCDD treatments. These data support the hypothesis that TCDD results in adverse effects on female reproductive function. However, the age of animals before or after puberty play an important role in the difference between results. Moreover, TCDD exposure on the GD 8 or 15 has a great concern in the results observed. الملخص العربي : قد أجريت هذه الدراسة للتعرف علي إمکانية تقييم آثار التعرض للديوکسين عن طريق الرحم والرضاعة على الوظيفة الإنجابية في ذرية الفئران الإناث، قبل وبعد سن البلوغ. قد تم إعطاء الديوکسين للجرذان الحوامل بجرعات 0 أو 1,0 ميکروغرام / کغ في يوم الحمل الثامن و الخامس عشر. وقد بدا فحص ذرية الإناث في فترة ما بعد الفطام قبل سن البلوغ في اليومالواحد والعشرون بعد الولادة وأيضا تم فحص ذرية الإناث في مرحلة ما بعد البلوغ في اليومالثاني و الأربعين بعد الولادة. وقد تم تقييم لمستوي الإباضة، و أيضا وقد تم عمل تحليل کيميائي حيوي لقياس نشاط کل من الهرمونات الخاصة بالجونادوتروبين وأيضا قياس مستوي هرمون الاستروجين والبروجستيرون في المصل وذلک باستخدام المقايسة المناعية الشعاعية، کما تم فحص هستومورفولوجي للمبيضين. وشمل التحليل العد والقياس والتصنيف لکل أنوع البصيلات والجريبات الغارية في جميع أنحاء المبيض بالکامل. وتشير النتائج إلى أن التعرض إلى الديوکسين قد أدي إلي خفض معنوي ملحوظ فى معدل التبويض، وأيضا في مستوي الهرمونات الخاصة بالجونادوتروبين في المصل، وأيضا في مستويات هرمون الاستروجين والبروجستيرون في المصل، وقد أدي التعرض للديوکسين إلي نقصاً معنوياً ملحوظاً في عدد الجريبات الغارية والبصيلات من فئات معينة حجم عندما تم الفحص الهستومورفولوجي للمبيض. کما أظهر الفحص المجهرى للمبيض من ذرية الفئران المعرضة للديوکسين، تحلل وفقد و تغير فى شکل الخلايا التي تتکون منها أنسجة البصيلات المسئولة عن الإباضة. بالنظر لهذة النتائج يمکن أن نستنتج أن هذه البيانات تدعم الفرضية القائلة بأن التعرض للديوکسين قد يؤدي الي آثار ضارة على الوظيفة التناسلية للإناث. مع الوضع في الاعتبار، إن عمر الحيوانات قبل أو بعد سن البلوغ تلعب دوراً هاماً في الفرق بين النتائج. وعلاوة على ذلک، قد تم ملاحظة أن وقت التعرض للديوکسين أثناء الحمل في اليوم الثامن أو الخامس عشر کان له تأثير واضح للفرق بين النتائج. | ||
| Keywords | ||
| Keywords: Dioxin; Ovary; LH; FSH; Estrogen; Ovarian Follicles | ||
| References | ||
|
REFERENCES:
Abdel rahim, M., Smith 3rd, R., Safe, S., 2003. Aryl hydrocarbon receptor gene silencing with small inhibi0tory RNA differentially modulates Ahresponsiveness in MCF-7 and HepG2 cancer cells. Mol. Pharmacol. 63, 1373–1381.
Aylward, L.L., Brunet, R.C., Carrier, G., Hays, S.M., Cushing, C.A.,
Needham, L.L., Patterson Jr., D.G., Gerthoux, P.M., Brambilla, P., Mocarelli, P., 2005. Concentration de Pendent TCDD elimination kinetics in humans: toxicokinetic modeling for moderately to highly exposed adults from Seveso, Italy, and Vienna, Austria, and impact on dose estimates for the NIOSH cohort. J. Expo. Anal. Environ. Epidemiol. 15, 51–65.
Bookstaff, R.C., Kamel, F., Moore, R.W., Bjerke, D.L. and Peterson, R.E. 1990. Altered regulation of pituitary gonadotropin- releasing hormone (GnRH) receptor number and pituitary responsiveness to GnRH in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated male rats. Toxicol. Appl. Pharmacol. 105, 78-92.
Boverhof, D.R., Kwekel, J.C., Humes, D.G., Burgoon, L.D., Zacharewski, T.R., 2006. Dioxin induces an estrogen-like, estrogen receptor-dependent gene expression response in the murine uterus. Mol. Pharmacol. 69,1599–1606.
Brunnberg, S., Andersson, P., Lindstam, M., Paulson, I., Poellinger, L., Hanberg, A., 2006. The constitutively active Ah receptor (CA-Ahr) mouse as a potential model for dioxin exposure – effects in vital organs. Toxicol. 224, 191–201.
Cao, J., Patisaul, H.B., Petersen, S.L., 2011. Aryl hydrocarbon receptor activation in lactotropes and gonadotropes interferes with estradiol-dependent and in dependent preprolactin, glycoprotein alpha and uteinizing hormone beta gene expression. Mol. Cell. ndocrinol. 333, 151–159.
Chaffin, C.L., Peterson, R.E., Hutz, R.J. 1996. In utero and lactational exposure of female Holtzman rats to 2,3,7,8 tetrachlorodibenzo-p-dioxin: modulation of the estrogen signal. Biol Reprod. 55: 62–7.
Chaffin, C.L, Trewin, A.L, Watanabe, G, Taya, K, Hutz, R.J. 1997. Alterations to the pituitary-gonadal axis in the peripubertal female rat exposed in utero and through lactation to 2,3,7,8-tetrachlorodibenzo-p-dioxin.Biol Reprod;56: 1498–502.
Chen, C-Y., Hamm, J.T., Hass, J.R., Birnbaum, L.S. 2001. Disposition of polychlorinated dibenzo pdioxins,dibenzofurans, and non-orthopolychlorinated biphenyls in pregnant Long Evans rats and the transfer to offspring. Toxicol. Appl Pharmacol .173:65–88.
Chu I, Villeneuve, D.C., Yagminas, A. 1995.Toxicity of PCB 77 (3,3_,4,4_-tetrachlorobiphenyl) and PCB 118 (2,3_,4,4_,5-pentachlorobiphenyl) in the rat following subchronic dietary exposure. Fundam Appl Toxicol. 26:282–92.
Dasmahapatra, A.K, Wimpee, B.A.B, Trewin, A.L, Wimpee, C.F, Ghorai, J.K, Hutz. R.J. 2000. Demonstration of 2,3,7,8-tetrachlorodibenzo-p-dioxin attenuation of P450 steroidogenic enzyme mRNAs in rat granulosa cell in vitro by competitive reverse transcriptase polymerase chain reaction assay. Mol Cell Endocrinol.164:5–18.
Edson, M.A., Nagaraja, A.K., Matzuk, M.M., 2009. The mammalian ovary from genesis to revelation. Endocr. Rev. 30: 624–712.
Eskenazi, B., Warner, M., Marks, A.R., Samuels, S., Gerthoux, P.M., Vercellini, P., Olive, D.L., Needham, L., Patterson Jr., D., 2005. Serum dioxin concentrations and age at menopause. Environ. Health. Perspect. 113: 858–862.
Flaws, A. J., Sommer, R. J., Silbergeld, E. K., Peterson, R. E., Hirshfieldt, A. N. 1997. In Utero and Lactational Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) Induces Genital Dysmorphogenesis in the Female Rat 1.Toxicol. App. Pharmacol. 147, 351-362.
Frakes, R.A., Zeeman, C.Q.,Mower, B. 1993. Bioaccumulation of 2,3,7,8-tetrachlorodibenzo pdioxin )TCDD) by fish downstream of pulp and papermills in Maine. Ecotoxicol. Environ. Saf. 25: 244–252.
Franczak, A., Nynca, A., Valdez, K.E., Mizinga, K.M., Petroff, B.K., 2006. Effects of acute and chronic exposure to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin on the transition to reproductive senescence in female Sprague–Dawley rats. Biol. Reprod. 74: 125–130.
Gao, X., Son, D.S., Terranova, P.F., Rozman, K.K., 1999a. Toxic equivalency factors of polychlorinated dibenzo-pdioxins in an ovulation model: validation of the toxic equivalency concept for one aspect of endocrine disruption. Toxicol. Appl. Pharmacol. 157: 107–116.
Gao, X., Terranova, P.F., Rozman, K.K., 1999b. Blockage of ovulation by polychlorinated furans (PCDFs), biphenyls (PCBs) and their mixture with dibenzo pdioxins (PCDDs) supports the toxic equivalency (TEQ) concept. Toxicol. Appl. Pharmacol. 163: 115–124.
Gao, X., Mizuyachi, K., Terranova, P.F, Rozman, K.K. 2001. 2,3,7,8- Tetrachlorodibenzo-p-dioxin decreases responsiveness of the hypothalamus to estradiol as a feedback inducer of preovulatory gonadotropin secretion in the immature gonadotropin-primed rat. Toxicol Appl Pharmacol. 170:181–90.
Gierthy, J.F., Lincoln, D.W., Gillespie, M.B., Seeger, J.I., Martinez, H.L., Dickerman, H.W., Kumar, S.A., 1988. Suppression of estrogen-regulated extracellular tissue plasminogen activator activity of MCF-7 cells by 2,3,7,8 tetrachlorodibenzo-p-dioxin. Cancer Res. 47: 6198–6203.
Gray, L.E, and Ostby, J.S. 1995. In utero 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) alters reproductive morphology and function in female rat offspring. Toxicol Appl Pharmacol. 133:285–94.
Gray, L.E, Wolf C, Mann P, Ostby, J.S. 1997. In utero exposure to low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin alters reproductive development of female Long Evance hooded rat offspring. Toxicol Appl Pharmacol. 146: 237–44.
Gregoraszczuk, E.L., Zabielny, E., Ochwat, D. 2001. Aryl hydrocarbon receptor (AhR)- linked inhibition of luteal cell progesterone secretion in 2,3,7,8-tetrachlorodibenzo-p-dioxin treated cells. J. Physiol. Pharmacol. 52: 303–311.
Grochowalski, A., Chrzaszcz, R., Pieklo, R.,Gregoraszczuk, E.L., 2001. Estrogenic and antiestrogenic effect of in vitro treatment of follicular cells with2,3,7,8-tetrachlorodibenzo-p-dioxin. Chemosphere.43:823–827.
Heimler, I., Trewin, A.L., Chaffin, C.L., Rawlins, R.G., Hutz, R.J.1998. Modulation of ovarian follicle maturation and effects on apoptotic cell death in holtzman rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in utero and lactationally. Reprod. Toxicol. 12: 69–73.
Hernández-Ochoa, I., Karman, B.N., Flaws, J.A., 2009. The role of the aryl hydrocarbon receptor in the female reproductive system. Biochem. Pharmacol.77:547–559.
Hirshfield, A.N., 1991. Development of follicles in the mammalian ovary. Int. Rev. Cytol. 43–101.
Hites, R.A., 2011. Dioxins: an overview and history. Environ. Sci. Technol. 45: 16–20.
Humblet, O., Williams, P.L., Korrick, S.A., Sergeyev, O., Emond, C.,Birnbaum, L.S., Burns,J.S., Altshul, L., Patterson Jr., D.G., Turner,W.E., Lee, M.M., Revich, B.,Hauser, R.,2011. Dioxin andpolychlorinated, biphenyl concentrations in mother's serum and the timing of pubertal onset in sons. Epidemiol. 22: 827–835.
Jablonska, O., Shi, Z., Valdez, K.E., Ting, A.Y., Petroff, B.K., 2010. Temporal and anatomical sensitivities to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin leading to premature acyclicity with age in rats. Int. J. Androl. 33: 405–412.
Kulkarni, P.S., Crespo, J.G., Afonso, C.A., 2008. Dioxins sources and current remediation technologies – a review. Environ. Int. 34:139–153.
Li, X., Johnson, D.C., Rozman, K.K.1995. Effects of 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) on estrous cycllicity and ovulation in female Sprague-Dawley rats. Toxicol. Lett. 78: 219-22238.
Li, X., Johnson, D.C, Rozman, K.K. 1997.2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD)increases release of luteinizing hormone and follicle-stimulating hormone from the pituitary of immature female rats in vivo and in vitro. Toxicol. Appl.harmacol.142:264–9.
Mably, T.A., Moore, R.W., Peterson, R.E. 1992. In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin.1. Effects on androgenic status. Toxicol Appl Pharmacol. 114:97–107.
MacLusky, N.J, Brown, T.J., Schantz, S, Seo, B.W., Peterson, R.E .1998. Hormonal interactions in the effects of halogenated aromatic hydrocarbons on the developing brain. Toxicol. Ind. Health 14: 185–208.
Miller, K., Borgeest, C., Greenfeld, C., Tomic, D., Flaws, J.,2004. In utero effects of chemicals on reproductive tissues in females. Toxicol. Appl. Pharmacol. 198:111-131.
Mizuyachi, K., Son, D.S., Rozman, K.K., Terranova, P.F. 2002. Alteration inovarian gene expression in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin: reduction of cyclooxygenase-2 in the blockage of ovulation. Reprod. Toxicol. 16: 299–307.
Morán, F.M., Conley, A.J., Corbin, C.J., Enan, E., VandeVoort, C., Overstreet, J.W., Lasley, B.L., 2000.2,3,7,8-Tetrachlorodibenzo-p-dioxin decreases estradiol production without altering the enzyme activity of cytochrome P450 aromatase of human luteinized granulosa cells in vitro. Biol. Reprod.62:1102–1108.
Morán, F.M., Vandevoort, C.A., Overstreet, J.W., Lasley, B.L., Conley, A.J., 2003a. Molecular target of endocrine disruption in human luteinizing granulosa cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin:inhibition of estradiol secretion due to decreased 17 alpha-hydroxylase/17,20-lyase cytochrome P450 expression. Endocrinol. 144:467–473.
Morán, F.M., Lohstroh, P., Vandevoort, C.A., Chen, J., Overstreet, J.W., Conley, A.J., Lasley, B.L., 2003b. Exogenous steroid substrate modifies the effect of 2,3,7,8-tetrachlorodibenzo -pdioxin on estradiol production of human luteinized granulosa cells in vitro. Biol. Reprod. 68: 244–251.
Myllymäki, S.A., Haavisto, T.E., Brokken, L.J., Viluksela, M., Toppari, J., Paranko, J. 2005. In utero and lactational exposure to TCDD; steroidogenic outcomes differ in male and female rat pups. Toxicol. Sci. 88: 534–544.
Ohtake, F., Takeyama, K., Matsumoto, T., Kitagawa, H., Yamamoto, Y., Nohara, K., Tohyama, C., Krust, A., Mimura, J., Chambon, P., Yanagisawa, J., Fujii-Kuriyama, Y., Kato, S., 2003. Modulation of oestrogen receptor signalling by association with the activated dioxin receptor. Nature. 423:545–550.
Ohtake, F., Baba, A., Takada, I., Okada, M., Iwasaki, K., Miki, H., Takahashi, S., Kouzmenko, A., Nohara, K., Chiba, T., Fujii-Kuriyama, Y., Kato, S., 2007. Dioxin receptor is a ligand-dependent E3 ubiquitin ligase. Nature. 446: 562–566.
Petroff BK, Gao X, Rozman KK, Terranova PF. 2000. Interaction of estradiol and 2,3,7,8-tetrchlorodibenzo-p-dioxin (TCDD) in an ovulation model: evidence for systemic potentiation and local ovarian effects. Reprod Toxicol.14:247–55.
Petroff BK, Gao X, Rozman KK, Terranova PF. 2001a.The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on weight gain and hepatic ethoxyresorufin-o-deethylase (EROD) induction vary with ovarian hormonal status in the immature gonadotropin-primed rat model. Reprod. Toxicol. 15:269–74.
Petroff, B.K., Roby, K.F., Gao, X., Son, D.S., Williamsn, S., Johnson, D., Rozman, K.K., Terranova, P.F., 2001b. A review of mechanisms controlling ovulation with implications for the anovulatory effects of polychlorinated dibenzo-p-dioxins in rodents. Toxicol. 158: 91–107.
Petroff, B.K., Croutch, C.R., Hunter, D.M., Wierman, M.E., Gao, X., 2003.2,3,7,8-Tetrachlorodibenzo-pdioxin (TCDD) stimulates gonadotropin secretion in the immature female Sprague–Dawley rat through a pentobarbital- and estradiol-sensitive mechanism but does not alter gonadotropin-releasing hormone (GnRH) secretion by immortalized GnRH neurons in vitro. Biol. Reprod. 68, 2100–2106.
Pesonen, S.A., Haavisto, T.E., Viluksela, M., Toppari, J., Paranko, J., 2006. Effects of in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) on rat follicular steroidogenesis. Reprod. Toxicol. 22: 521–528.
Pohjanvirta, R., Unkila, M., Tuomisto, J. 1994. TCDD-induced hypophagia is not explained by nausea. Pharmacol. Biochem. Behav. 47: 273–282.
Romkes, M., Piskorska-Pliszczynska, J., Safe, S. 1987. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on hepatic and uterine estrogen receptor levels in rats.Toxicol. Appl. Pharmacol. 87: 1–9.
Safe, S.H. 1995. Modulation of gene expression and endocrine response pathwaysby2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds. Pharmacol. Ther. 67: 247–281.
Salisbury, T.B, and Marcinkiewicz, J.L. 2002. In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,3,4,7,8-pentachlorodibenzofuran redices growth and disrupts reproductive parameters in female rats. Biol Reprod. 66:1621–6.
Schecter, A., Birnbaum, L., Ryan, J.J., Constable, J.D., 2006. Dioxins: an overview. Environ. Res. 101: 419–428.
Shi, Z., Valdez, K.E., Ting, A.Y., Franczak, A., Gum, S.L., Petroff, B.K. 2007. Ovarian endocrine disruption underlies premature reproductive senescence following environmentally relevant chronic exposure to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin. Biol.Reprod. 76: 198–202.
Smith, M.S., Freeman, M.E. and Neill, J.D. 1975. The control of progesterone secretion during the estrous cycle and early pseudopregnancy in the rat: prolactin, gonadotropin and steroid levels associated with rescue of the corpus luteum of pseudopregnancy. Endocrinol. 96: 219-226.
Son, D.S., Ushinohama, K., Gao, X., Taylor, C.C., Roby, K.F., Rozman, K.K., Terranova, P.F., 1999.2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) blocks ovulation by a direct effect on the ovary without alteration of ovarian steroidogenesis: lack of a direct effect on ovarian granulosa and theca – interstitial cell steroidogenesis in vitro. Reprod. Toxicol. 13: 521–530.
Taya K, Terranova PF and Greenwald GS .1981. Acute effects of exogenous progesterone on follicular steroidogenesis in the cyclic rat Endocrinol. 108: 2324–2330.
Terranova PF, Garza F. 1983. Relationship between the preovulatory luteinizing hormone (LH) surge and androstenedione synthesis of preantral follicles in the cyclic hamster: detection by in vitro responses to LH. Biol. Reprod. 29: 630–6.
Tischkau, S. A., Jaeger,C. D., Krager, S.L. 2011 Circadian clock disruption in the mouse ovary in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicology Letters 201: 116–122.
Travis, C.C., Hattemer-Frey, H.A. 1991. Human exposure to dioxin. Sci. Total Environ. 104: 97–127.
Tsutsumi, O., Uechi, H., Sone, H., Yonemoto, J., Takai, Y., Momoeda, M., Tohyama, C., Hashimoto, S., Morita, M., Taketani, Y. 2011. Presence of dioxins in human follicular fluid: their possible stage-specific action on the development ofpreimplantationmouse embryos. Biochem. Biophys. Res.Commun. 250: 498–501.
Tuppurainen, K., Asikainen, A., Ruokojärvi, P., Ruuskanen, J. 2003. Perspectives on theformation of polychlorinated dibenzo-p-dioxins and dibenzofurans during municipal solid waste (MSW) incineration and other combustion processes. Acc. Chem.Res. 36, 652–658.
Warner, M., Eskenazi, B., Olive, D.L., Samuels, S., Quick-Miles, S., Vercellini, P., Mocarelli, P., 2007. Serum dioxin concentrations and quality of ovarian function in women of Seveso. Environ. Health. Perspect. 115: 336–340.
Watanabe, H., Suzuki, A., Goto, M., Ohsako, S., Tohyama, C., Handa, H., Iguchi, T., 2004. Comparative uterine gene expression analysis after dioxin and estradiol administration. J. Mol. Endocrinol. 33: 763–771.
Wyde ME, Eldridge SR, Lucier GW, Walker NJ. 2001.Regulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin induced tumor promotion by 17_-estradiol in female Sprague–Dawley rats. Toxicol. Appl. Pharmacol.173:7–17.
Ulaszewska, M.M., Zuccato, E., Davoli, E. 2011. PCDD/Fs and dioxin-like PCBs in human milk and estimation of infants' daily intake: a review. Chemosphere. 83: 774–782.
Yonemoto, J. 2000. The Effects of Dioxin on Reproduction and Development. J. Ind . Health. 38: 259–268. | ||
|
Statistics Article View: 162 PDF Download: 176 |
||
