DOI QR코드

DOI QR Code

Effects of Methyl Mercury Exposure on Placental Efficiency and Fetal Growth Retardation in Rats

메틸수은 노출이 흰쥐의 태반 효율과 태아 성장에 미치는 영향

  • Lee, Chae Kwan (Institute of Environmental and Occupational Medicine & Department of Occupational and Environmental Medicine, Busan Paik Hospital, Inje University)
  • 이채관 (인제대학교 의과대학 환경.산업의학연구소 & 부산백병원 직업환경의학과)
  • Received : 2020.06.10
  • Accepted : 2020.06.20
  • Published : 2020.08.31

Abstract

Objectives: Some animal studies have reported that methyl mercury causes developmental toxicities such as placental and fetal weight loss, but the mechanism is still unclear. This study aimed to investigate the developmental toxicities of methyl mercury, focusing on placental endocrine function and fetal growth retardation in rats. Methods: Positively same-time-mated female Sprague-Dawley rats were purchased on gestational day (GD) eight and treated with 0, 5, 10 and 20 ppm of methyl mercury (n=5) dissolved in tap water from GD eight through 19. During treatment, the drinking water (methyl mercury) intake and body weight of each pregnant rat was measured daily. On day 19, caesarean sections were performed and blood samples were collected. Developmental data such as placental and fetal weights, fetus numbers, and placental efficiency (fetal weight/placental weight) were also collected. Placental prolactin-growth hormone (PRL-GH) family, such as placental lactogen (PL) -Iv, II, and prolactin-like protein (PLP) -B, levels in serum were analyzed by ELISA. Also, placental tissues were assigned to histochemistry. Results: The mean cumulative methyl mercury exposure for the 5, 10, and 20 ppm groups were 2.37, 4.63, and 9.66 mg, respectively. The mean daily exposure of the 5, 10, and 20 ppm groups were 0.24, 0.47, and 0.97 mg, respectively. Maternal body weight increased in accordance with GD. There was no significant difference in weight gain among the experimental groups. Histopathologic changes were not observed in placental tissues among the experimental groups. However, mean placental and fetal weights were lower in the 10 and 20 ppm exposed groups compared to the control. Placental efficiency was also lower in the 10 and 20 ppm exposed groups compared to the control. Serum PL-Iv and II levels were lower in the 10 and 20 ppm exposed groups than the control, in accordance with the changing pattern of placental and fetal weights and placental efficiency. Conclusion: The inhibitory effects of methyl mercury on the serum levels of placental PRL-GH family such as PL-Iv and II may be secondary leads to the reduction of placental efficiency and fetal growth retardation in rats.

Keywords

References

  1. Stacey NH, Klaasen CD. Comparison of the effects of metals on cellular injury and lipid peroxidation in isolated rat hepatocytes. J Toxicol Environ Health. 1980; 7: 139-147. https://doi.org/10.1080/15287398109529965
  2. Roman HA, Walsh TL, Coull BA, Dewailly E, Guallar E, Hattis D, et al. Evaluation of the cardiovascular effects of methylmercury exposures: current evidence supports development of a doseresponse function for regulatory benefits analysis. Environ Health Perspect. 2011; 119: 607-614. https://doi.org/10.1289/ehp.1003012
  3. NIER (National Institute of Environmental Research). Annual report of the National Environmental Health Survey (KoNEHS). 2018.
  4. NIER (National Institute of Environmental Research). Annual report of the National Environmental Health Survey (KoNEHS). 2012.
  5. Rice DC, Schoeny R, Mahaffey K. Methods and rationale for derivation of a reference dose for methylmercury by the U.S. EPA. Risk analysis: an official publication of the Society for Risk Analysis. 2003; 23: 107-115. https://doi.org/10.1111/1539-6924.00294
  6. Yanga Z, Zhaoa Y, Lia Q, Shaoa Y, Yua X, Congb W, et al. Developmental exposure to mercury chloride impairs social behavior in male offspring dependent on genetic background and maternal autoimmune environment. Toxicology and Applied Pharmacology. 2019; 370: 1-13. https://doi.org/10.1016/j.taap.2019.03.006
  7. Kabuto M. Acute endocrine effects of a single administration of methylmercury chloride (MMC) in rats. Endocrinol Jpn. 1986; 33: 683-690. https://doi.org/10.1507/endocrj1954.33.683
  8. Vahter M, Akesson A, Lind B, Bjors U, Schutz A, Berglund M. Longitudinal study of methylmercury and inorganic mercury in blood and urine of pregnant and lactating women, as well as in 71 umbilical cord. Environmental Research. 2000; 84: 186-194. https://doi.org/10.1006/enrs.2000.4098
  9. Curle R, Persaud A. In vivo evaluation of teratogenesis and cytogenetic changes following methylmercuric chloride treatment. The Anatomical Record. 1987; 219: 289-295.
  10. Weng Z, Liu Z, Zhang S, Tao H, Ji X. Zinc Protection in Fetal Rats for Maternal Mercury Exposure-Induced Growth Retardation Is Probably Associated With S100B Expression. J Obstet Gynaecol Res. 2017; 43: 73-77. https://doi.org/10.1111/jog.13175
  11. Kim DS, Ahn SC, Chung HU, Kwon YM, Choi KH. A Study on Schoolchildren's Mercury Exposure and Related Health Effects in High Mercury Exposure Areas in Korea. J Environ Health Sci. 2015; 41: 268-276.
  12. Kim BM, Lee BE, Hong YC, Park H, Ha M, Kim YJ, et al. Mercury levels in maternal and cord blood and attained weight through the 24 months of life. Sci Total Environ. 2011; 410: 26-33. https://doi.org/10.1016/j.scitotenv.2011.08.060
  13. Robertson MC, Cosby H, Fresnoza A, Cattini PA, Shiu RP, et al. Expression, purification, and characterization of recombinant rat placental lactogen-I: a comparison with the native hormone. Endocrinology. 1994; 134: 393-400. https://doi.org/10.1210/en.134.1.393
  14. Dai G, Liu B, Szpirer C, Levan G, Kwok SC, et al. Prolactin-like protein-C variant: complementary deoxyribonucleic acid, unique six exon gene structure, and trophoblast cell-specific expression. Endocrinology. 1996; 137: 5009-5019. https://doi.org/10.1210/en.137.11.5009
  15. Forsyth I. Prolactin, growth hormones, and placental lactogens: an historical perspective. J Mammary Gland Biol Neoplasia. 1997; 2: 3-6.
  16. Lee CK, Kang SG, Lee JT, Lee SW, Kim JH, Son BC et al. Effects of perfluorooctane sulfuric acid on placental PRL-family hormone production and fetal growth retardation in mice. Molecular and Cellular Endocrinology. 2015; 401: 165-172. https://doi.org/10.1016/j.mce.2014.10.026
  17. Li J, Zhang N, Zhang Y, Hu X, Gao G, Ye Y, et al. Human placental lactogen mRNA in maternal plasma play a role in prenatal diagnosis of abnormally invasive placenta: yes or no? Gynecol Endocrinol. 2019; 35: 631-634. https://doi.org/10.1080/09513590.2019.1576607
  18. Lee JH. Methylmercuric chloride (MMC) and reduction of the fetal ossification in fisher-334 rats furing organogenesis. J Environ Health Sci. 2001; 27: 73-87.
  19. Oliveira CS, Oliveira VA, Costa LM, Pedroso TF, Fonseca MM, Bernardi JS, et al. Inorganic Mercury Exposure in Drinking Water Alters Essential Metal Homeostasis in Pregnant Rats Without Altering Rat Pup Behavior. Reprod Toxicol. 2016; 65: 18-23. https://doi.org/10.1016/j.reprotox.2016.06.013
  20. Simmons DG, Rawn S, Davies A, Hughes M, Cross JC. Spatial and temporal expression of the 23 murine Prolactin/Placental Lactogen-related genes is not associated with their position in the locus. BMC Genomics. 2008; 9: 352-373. https://doi.org/10.1186/1471-2164-9-352
  21. Thordarson G, Galosy S, Gudmundsson GO, Newcomer B, Sridaran R, et al. Interaction of mouse placental lactogens and androgens in regulating progesterone release in cultured mouse luteal cells. Endocrinology. 1997; 138: 3236-3241. https://doi.org/10.1210/en.138.8.3236
  22. Telleria CM, Zhong L, Deb S, Srivastava RK, Park KS, et al. Differential expression of the estrogen receptors alpha and beta in the rat corpus luteum of pregnancy: regulation by prolactin and placental lactogens. Endocrinology. 1998; 139: 2432-2442. https://doi.org/10.1210/en.139.5.2432
  23. Conliffe PR, Simmen RC, Buhi WC, Shiverick KT. Cloning of a novel rat placental prolactin-like protein C-related cDNA. Mol Reprod Dev. 1995; 41: 167-176. https://doi.org/10.1002/mrd.1080410207
  24. Cohick CB, Xu L, Soares MJ. Prolactin-like protein-B: heterologous expression and characterization of placental and decidual species. J Endocrinol. 1997; 152: 291-302. https://doi.org/10.1677/joe.0.1520291
  25. Rasmussen CA, Orwig KE, Vellucci S, Soares MJ. Dual expression of prolactin-related protein in decidua and trophoblast tissues during pregnancy in rats. Biol Reprod. 1997; 56: 647-654. https://doi.org/10.1095/biolreprod56.3.647
  26. Lee CK, Lee JT, Yu SJ, Kang SG, Moon CS et al. Effects of cadmium on the expression of placental lactogens and Pit-1 genes in the rat placental trophoblast cells. Molecular and Cellular Endocrinology. 2009; 298: 11-18. https://doi.org/10.1016/j.mce.2008.09.028
  27. Bodner M, Karin M. A pituitary-specific transacting factor can stimulate transcription from the growth hormone promoter in extracts of nonexpressing cells. Cell. 1987; 50: 267-275. https://doi.org/10.1016/0092-8674(87)90222-4
  28. Bamberger AM, Bamberger CM, Pu LP, Puy LA, Loh YP, et al. Expression of pit-1 messenger ribonucleic acid and protein in the human placenta. J Clin Endocrinol Metab. 1995; 80: 2021-2026. https://doi.org/10.1210/jc.80.7.2021
  29. Lee CK, Kang HS, Lee BJ, Kang HM, Choi WS, et al. Effects of dopamine and estrogen on the regulation of Pit-1 alpha, Pit-2 beta and PL-II gene expression in the rat placenta. Mol Cells. 1998; 8: 205-211.
  30. Roby KF, Soares MJ. Trophoblast cell differentiation and organization: role of fetal and ovarian signals. Placenta. 1993; 14: 529-545. https://doi.org/10.1016/S0143-4004(05)80206-1
  31. Cronier L, Guibourdenche J, Niger C, Malassine A. Oestradiol stimulates morphological and functional differentiation of human villous cytotrophoblast. Placenta. 1999; 20: 669-676. https://doi.org/10.1053/plac.1999.0423
  32. Zhanag X, Wang Y, Zhao Y, Chen X. Experimental study on the estrogen-like effect of mercuric chloride. Biometals. 2008; 21: 145-150.