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Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

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General Research Article

Hypothyroidism Alters the Uterine Lipid Levels in Pregnant Rabbits and Affects the Fetal Size

Author(s): Julia Rodríguez-Castelán, Dafne Zepeda-Pérez, Maribel Méndez-Tepepa, Marlenne Castillo-Romano, Marlen Espíndola-Lozano, Arely Anaya-Hernández, Pere Berbel and Estela Cuevas-Romero*

Volume 19, Issue 6, 2019

Page: [818 - 825] Pages: 8

DOI: 10.2174/1871530318666181102093621

Abstract

Background: Hypothyroidism has been related to low-weight births, abortion and prematurity, which have been associated with changes in the content of glycogen and vascularization of the placenta. Since hypothyroidism can cause dyslipidemia, it may affect the lipid content in the uterus affecting the development of fetuses.

Objective: To investigate the effect of hypothyroidism on the lipid levels in serum and uterus during pregnancy and their possible association with the size of fetuses.

Method: Adult female rabbits were grouped in control (n = 6) and hypothyroid (n = 6; treated with methimazole for 29 days before and 19 days after copulation). Food intake and body weight were daily registered. At gestational day 19 (GD19), dams were sacrificed under an overdose of anesthesia. Morphometric measures of fetuses were taken. Total cholesterol (TC), triglyceride (TAG), and glucose concentrations were quantified in blood, uterus and ovaries of dams. The expression of uterine 3β- hydroxysteroid dehydrogenase (3β-HSD) was quantified by Western blot.

Results: Hypothyroidism reduced food intake and body weight of dams, as well as promoted low abdominal diameters of fetuses. It did not induce dyslipidemia and hyperglycemia at GD19 and did not modify the content of lipids in the ovary. However, it reduced the content of TAG and TC in the uterus, which was associated with uterine hyperplasia and an increased expression of 3β-HSD in the uterus.

Conclusion: Hypothyroidism alters the lipid content in the uterus that might subsequently affect the energy production and lipid signaling important to fetal development.

Keywords: Thyroid hormones, total cholesterol, triglyceride, 3β-HSD, endometrium, methimazole.

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[1]
Ribeiro, E.S.; Santos, J.E.P.; Thatcher, W.W. Role of lipids on elongation of the preimplantation conceptus in ruminants. Reproduction, 2016, 152(4), R115-R126.
[http://dx.doi.org/10.1530/REP-16-0104] [PMID: 27335133]
[2]
Père, M-C.; Etienne, M. Nutrient uptake of the uterus during the last third of pregnancy in sows: Effects of litter size, gestation stage and maternal glycemia. Anim. Reprod. Sci., 2018, 188, 101-113.
[http://dx.doi.org/10.1016/j.anireprosci.2017.11.014] [PMID: 29187294]
[3]
Wathes, D.C.; Clempson, A.M.; Pollott, G.E. Associations between lipid metabolism and fertility in the dairy cow. Reprod. Fertil. Dev., 2012, 25(1), 48-61.
[http://dx.doi.org/10.1071/RD12272] [PMID: 23244828]
[4]
Dean, M.; Hunt, J.; McDougall, L.; Rose, J. Uterine glycogen metabolism in mink during estrus, embryonic diapause and pregnancy. J. Reprod. Dev., 2014, 60(6), 438-446.
[http://dx.doi.org/10.1262/jrd.2014-013] [PMID: 25225159]
[5]
Catov, J.M.; Bodnar, L.M.; Kip, K.E.; Hubel, C.; Ness, R.B.; Harger, G.; Roberts, J.M. Early pregnancy lipid concentrations and spontaneous preterm birth. Am. J. Obstet. Gynecol., 2007, 197(6), 610.e1-610.e7.
[http://dx.doi.org/10.1016/j.ajog.2007.04.024] [PMID: 18060950]
[6]
Chen, X.; Scholl, T.O.; Stein, T.P.; Steer, R.A.; Williams, K.P. Maternal Circulating Lipid Profile during Early Pregnancy: Racial/Ethnic Differences and Association with Spontaneous Preterm Delivery. Nutrients, 2017, 9(1), 9.
[http://dx.doi.org/10.3390/nu9010019] [PMID: 28045435]
[7]
Jiang, S.; Jiang, J.; Xu, H.; Wang, S.; Liu, Z.; Li, M.; Liu, H.; Zheng, S.; Wang, L.; Fei, Y.; Li, X.; Ding, Y.; Wang, Z.; Yu, Y. Maternal dyslipidemia during pregnancy may increase the risk of preterm birth: A meta-analysis. Taiwan. J. Obstet. Gynecol., 2017, 56(1), 9-15.
[http://dx.doi.org/10.1016/j.tjog.2016.07.012] [PMID: 28254234]
[8]
Ornoy, A.; Reece, E.A.; Pavlinkova, G.; Kappen, C.; Miller, R.K. Effect of maternal diabetes on the embryo, fetus, and children: congenital anomalies, genetic and epigenetic changes and developmental outcomes. Birth Defects Res. C Embryo Today, 2015, 105(1), 53-72.
[http://dx.doi.org/10.1002/bdrc.21090] [PMID: 25783684]
[9]
Weiner, E.; Barber, E.; Feldstein, O.; Schreiber, L.; Dekalo, A.; Mizrachi, Y.; Bar, J.; Kovo, M. The placental component and neonatal outcome in singleton vs. twin pregnancies complicated by gestational diabetes mellitus. Placenta, 2018, 63, 39-44.
[http://dx.doi.org/10.1016/j.placenta.2018.01.010] [PMID: 29486855]
[10]
Arbib, N.; Hadar, E.; Sneh-Arbib, O.; Chen, R.; Wiznitzer, A.; Gabbay-Benziv, R. First trimester thyroid stimulating hormone as an independent risk factor for adverse pregnancy outcome. J. Matern. Fetal Neonatal Med., 2017, 30(18), 2174-2178.
[http://dx.doi.org/10.1080/14767058.2016.1242123] [PMID: 27677438]
[11]
Hou, J.; Yu, P.; Zhu, H.; Pan, H.; Li, N.; Yang, H.; Jiang, Y.; Wang, L.; Wang, B.; Wang, Y.; You, L.; Chen, S. The impact of maternal hypothyroidism during pregnancy on neonatal outcomes: a systematic review and meta-analysis. Gynecol. Endocrinol., 2016, 32(1), 9-13.
[http://dx.doi.org/10.3109/09513590.2015.1104296] [PMID: 26527131]
[12]
Maraka, S.; Ospina, N.M.S.; O’Keeffe, D.T.; Espinosa De Ycaza, A.E.; Gionfriddo, M.R.; Erwin, P.J.; Coddington, C.C., III; Stan, M.N.; Murad, M.H.; Montori, V.M. Subclinical Hypothyroidism in Pregnancy: A Systematic Review and Meta-Analysis. Thyroid, 2016, 26(4), 580-590.
[http://dx.doi.org/10.1089/thy.2015.0418] [PMID: 26837268]
[13]
Silva, J.F.; Vidigal, P.N.; Galvão, D.D.; Boeloni, J.N.; Nunes, P.P.; Ocarino, N.M.; Nascimento, E.F.; Serakides, R. Fetal growth restriction in hypothyroidism is associated with changes in proliferative activity, apoptosis and vascularisation of the placenta. Reprod. Fertil. Dev., 2012, 24(7), 923-931.
[http://dx.doi.org/10.1071/RD11219] [PMID: 22935153]
[14]
Anaya-Hernández, A.; Rodríguez-Castelán, J.; Nicolás, L.; Martínez-Gómez, M.; Jiménez-Estrada, I.; Castelán, F.; Cuevas, E. Hypothyroidism affects differentially the cell size of epithelial cells among oviductal regions of rabbits. Reprod. Domest. Anim., 2015, 50(1), 104-111.
[http://dx.doi.org/10.1111/rda.12455] [PMID: 25405800]
[15]
Dukelow, W.R.; Williams, W.L. Survival of capacitated spermatozoa in the oviduct of the rabbit. J. Reprod. Fertil., 1967, 14(3), 477-479.
[http://dx.doi.org/10.1530/jrf.0.0140477] [PMID: 6071013]
[16]
Rodríguez-Castelán, J.; Méndez-Tepepa, M.; Carrillo-Portillo, Y.; Anaya-Hernández, A.; Rodríguez-Antolín, J.; Zambrano, E.; Castelán, F.; Cuevas-Romero, E. Hypothyroidism Reduces the Size of Ovarian Follicles and Promotes Hypertrophy of Periovarian Fat with Infiltration of Macrophages in Adult Rabbits. BioMed Res. Int., 2017. 20173795950
[http://dx.doi.org/http://10.1155/2017/3795950] [PMID: 28133606]
[17]
Rodríguez-Castelán, J.; Méndez-Tepepa, M.; Rodríguez-Antolín, J.; Castelán, F.; Cuevas-Romero, E. Hypothyroidism affects lipid and glycogen content and peroxisome proliferator-activated receptor δ expression in the ovary of the rabbit. Reprod. Fertil. Dev., 2018, 30(10), 1380-1387.
[http://dx.doi.org/10.1071/RD17502] [PMID: 29720336]
[18]
Frank, N.; Sojka, J.E.; Latour, M.A.; McClure, S.R.; Polazzi, L. Effect of hypothyroidism on blood lipid concentrations in horses. Am. J. Vet. Res., 1999, 60(6), 730-733.
[PMID: 10376902]
[19]
Choo, E.; Dando, R. The Impact of Pregnancy on Taste Function. Chem. Senses, 2017, 42(4), 279-286.
[http://dx.doi.org/10.1093/chemse/bjx005] [PMID: 28334158]
[20]
Calvino, C.; Império, G.E.; Wilieman, M. Costa-E-Sousa, R.H.; Souza, L.L.; Trevenzoli, I.H.; Pazos-Moura, C.C. Hypothyroidism Induces Hypophagia Associated with Alterations in Protein Expression of Neuropeptide Y and Proopiomelanocortin in the Arcuate Nucleus, Independently of Hypothalamic Nuclei-Specific Changes in Leptin Signaling. Thyroid, 2016, 26(1), 134-143.
[http://dx.doi.org/10.1089/thy.2015.0384] [PMID: 26538454]
[21]
Chan, S.Y.; Franklyn, J.A.; Pemberton, H.N.; Bulmer, J.N.; Visser, T.J.; McCabe, C.J.; Kilby, M.D. Monocarboxylate transporter 8 expression in the human placenta: the effects of severe intrauterine growth restriction. J. Endocrinol., 2006, 189(3), 465-471.
[http://dx.doi.org/10.1677/joe.1.06582] [PMID: 16731778]
[22]
Rodríguez-Castelán, J.; Anaya-Hernández, A.; Méndez-Tepepa, M.; Martínez-Gómez, M.; Castelán, F.; Cuevas-Romero, E. Distribution of thyroid hormone and thyrotropin receptors in reproductive tissues of adult female rabbits. Endocr. Res., 2017, 42(1), 59-70.
[http://dx.doi.org/10.1080/07435800.2016.1182185] [PMID: 27268091]
[23]
Galton, V.A.; Martinez, E.; Hernandez, A.; St Germain, E.A.; Bates, J.M.; St Germain, D.L. The type 2 iodothyronine deiodinase is expressed in the rat uterus and induced during pregnancy. Endocrinology, 2001, 142(5), 2123-2128.
[http://dx.doi.org/10.1210/endo.142.5.8169] [PMID: 11316780]
[24]
Galton, V.A.; Martinez, E.; Hernandez, A.; St Germain, E.A.; Bates, J.M.; St Germain, D.L. Pregnant rat uterus expresses high levels of the type 3 iodothyronine deiodinase. J. Clin. Invest., 1999, 103(7), 979-987.
[http://dx.doi.org/10.1172/JCI6073] [PMID: 10194470]
[25]
Huang, S.A.; Dorfman, D.M.; Genest, D.R.; Salvatore, D.; Larsen, P.R. Type 3 iodothyronine deiodinase is highly expressed in the human uteroplacental unit and in fetal epithelium. J. Clin. Endocrinol. Metab., 2003, 88(3), 1384-1388.
[http://dx.doi.org/10.1210/jc.2002-021291] [PMID: 12629133]
[26]
Teng, W.; Shan, Z.; Patil-Sisodia, K.; Cooper, D.S. Hypothyroidism in pregnancy. Lancet Diabetes Endocrinol., 2013, 1(3), 228-237.
[http://dx.doi.org/10.1016/S2213-8587(13)70109-8] [PMID: 24622371]
[27]
Bolarinwa, A.F.; Olaleye, S.B. Blastocyst implantation: effect of thyroidectomy and thyroxine replacement in the rat. Afr. J. Med. Med. Sci., 1997, 26(3-4), 135-137.
[PMID: 10456155]
[28]
Martínez-Gómez, M.; Juárez, M.; Distel, H.; Hudson, R. Overlapping litters and reproductive performance in the domestic rabbit. Physiol. Behav., 2004, 82(4), 629-636.
[http://dx.doi.org/10.1016/j.physbeh.2004.05.011] [PMID: 15327910]
[29]
Erenberg, A.; Omori, K.; Menkes, J.H. O, W.; Fisher, D.A. Growth and development of the thyroidectomized ovine fetus. Pediatr. Res., 1974, 8(9), 783-789.
[http://dx.doi.org/10.1203/00006450-197409000-00001] [PMID: 4413605]
[30]
Silva, J.F.; Ocarino, N.M.; Serakides, R. Maternal thyroid dysfunction affects placental profile of inflammatory mediators and the intrauterine trophoblast migration kinetics. Reproduction, 2014, 147(6), 803-816.
[http://dx.doi.org/10.1530/REP-13-0374] [PMID: 24534949]
[31]
Rodríguez-Castelán, J.; Nicolás, L.; Morimoto, S.; Cuevas, E. The Langerhans islet cells of female rabbits are differentially affected by hypothyroidism depending on the islet size. Endocrine, 2015, 48(3), 811-817.
[http://dx.doi.org/10.1007/s12020-014-0418-4] [PMID: 25213470]
[32]
Crouse, M.S.; McLean, K.J.; Crosswhite, M.R.; Reynolds, L.P.; Dahlen, C.R.; Neville, B.W.; Borowicz, P.P.; Caton, J.S. Nutrient transporters in bovine uteroplacental tissues on days sixteen to fifty of gestation. J. Anim. Sci., 2016, 94(11), 4738-4747.
[http://dx.doi.org/10.2527/jas.2016-0857] [PMID: 27898936]
[33]
Montelongo, A.; Lasunción, M.A.; Pallardo, L.F.; Herrera, E. Longitudinal study of plasma lipoproteins and hormones during pregnancy in normal and diabetic women. Diabetes, 1992, 41(12), 1651-1659.
[http://dx.doi.org/10.2337/diab.41.12.1651] [PMID: 1446807]
[34]
López-Soldado, I.; Ortega-Senovilla, H.; Herrera, E. Maternal adipose tissue becomes a source of fatty acids for the fetus in fasted pregnant rats given diets with different fatty acid compositions. Eur. J. Nutr., 2018, 57(8), 2963-2974.
[http://dx.doi.org/10.1007/s00394-017-1570-4] [PMID: 29127477]
[35]
Kong, L.; Wei, Q.; Fedail, J.S.; Shi, F.; Nagaoka, K.; Watanabe, G. Effects of thyroid hormones on the antioxidative status in the uterus of young adult rats. J. Reprod. Dev., 2015, 61(3), 219-227.
[http://dx.doi.org/10.1262/jrd.2014-129] [PMID: 25797533]
[36]
Brown, S.H.J.; Eather, S.R.; Freeman, D.J.; Meyer, B.J.; Mitchell, T.W. A Lipidomic Analysis of Placenta in Preeclampsia: Evidence for Lipid Storage. PLoS One, 2016, 11(9)e0163972
[http://dx.doi.org/10.1371/journal.pone.0163972] [PMID: 27685997]
[37]
Männistö, T.; Karumanchi, S.A.; Pouta, A.; Vääräsmäki, M.; Mendola, P.; Miettola, S.; Surcel, H-M.; Bloigu, A.; Ruokonen, A.; Järvelin, M-R.; Hartikainen, A-L.; Suvanto, E. Preeclampsia, gestational hypertension and subsequent hypothyroidism. Pregnancy Hypertens., 2013, 3(1), 21-27.
[http://dx.doi.org/10.1016/j.preghy.2012.09.001] [PMID: 23439671]
[38]
Herington, J.L.; O’Brien, C.; Robuck, M.F.; Lei, W.; Brown, N.; Slaughter, J.C.; Paria, B.C.; Mahadevan-Jansen, A.; Reese, J. Prostaglandin-Endoperoxide Synthase 1 Mediates the Timing of Parturition in Mice Despite Unhindered Uterine Contractility. Endocrinology, 2018, 159(1), 490-505.
[http://dx.doi.org/10.1210/en.2017-00647] [PMID: 29029054]
[39]
Parija, S.C.; Mishra, S.K.; Raviprakash, V. Hypothyroid state reduces calcium channel function in 18-day pregnant rat uterus. Indian J. Exp. Biol., 2006, 44(1), 19-27.
[PMID: 16430086]
[40]
Corriveau, S.; Pasquier, J.C.; Blouin, S.; Bellabarba, D.; Rousseau, É. Chronic levothyroxine and acute T3 treatments enhance the amplitude and time course of uterine contractions in human. Am. J. Physiol. Endocrinol. Metab., 2013, 304(5), E478-E485.
[http://dx.doi.org/10.1152/ajpendo.00346.2012] [PMID: 23249699]
[41]
Jayasingh, I.A.; Puthuran, P. Subclinical hypothyroidism and the risk of hypercholesterolemia. J. Family Med. Prim. Care, 2016, 5(4), 809-816.
[http://dx.doi.org/10.4103/2249-4863.201177] [PMID: 28348996]
[42]
Chatuphonprasert, W.; Jarukamjorn, K.; Ellinger, I. Physiology and Pathophysiology of Steroid Biosynthesis, Transport and Metabolism in the Human Placenta. Front. Pharmacol., 2018, 9, 1027.
[http://dx.doi.org/10.3389/fphar.2018.01027] [PMID: 30258364]
[43]
Pan, J.L.; Yuan, D.Z.; Zhao, Y.B.; Nie, L.; Lei, Y.; Liu, M.; Long, Y.; Zhang, J.H.; Blok, L.J.; Burger, C.W.; Yue, L.M. Progesterone-induced miR-133a inhibits the proliferation of endometrial epithelial cells. Acta Physiol. (Oxf.), 2017, 219(3), 683-692.
[http://dx.doi.org/10.1111/apha.12762] [PMID: 27458709]
[44]
Gultiken, N.; Yarim, M.; Yarim, G.F.; Gacar, A.; Mason, J.I. Expression of 3β-hydroxysteroid dehydrogenase in ovarian and uterine tissue during diestrus and open cervix cystic endometrial hyperplasia-pyometra in the bitch. Theriogenology, 2016, 86(2), 572-578.
[http://dx.doi.org/10.1016/j.theriogenology.2016.02.006] [PMID: 27020880]
[45]
Soleymani, E.; Ziari, K.; Rahmani, O.; Dadpay, M.; Taheri-Dolatabadi, M.; Alizadeh, K.; Ghanbarzadeh, N. Histopathological findings of endometrial specimens in abnormal uterine bleeding. Arch. Gynecol. Obstet., 2014, 289(4), 845-849.
[http://dx.doi.org/10.1007/s00404-013-3043-1] [PMID: 24121689]
[46]
Hu, Y.; Wang, Q.; Li, G.; Sun, X.; Liu, C. Ultrasonic morphology of uterus and ovaries in girls with pituitary hyperplasia secondary to primary hypothyroidism. Horm. Metab. Res., 2013, 45(9), 669-674.
[http://dx.doi.org/10.1055/s-0033-1345141] [PMID: 23670347]

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