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Thyroid hormones alter the transcriptome of in vitro-produced bovine blastocysts

Published online by Cambridge University Press:  23 June 2015

Fazl A. Ashkar ,
Tamas Revay ,
NaYoung Rho ,
Pavneesh Madan ,
Isabelle Dufort ,
Claude Robert ,
Laura A. Favetta ,
Chris Schmidt  and
W. Allan King
Fazl A. Ashkar
Affiliation:
Department of Biomedical Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada.
Tamas Revay
Affiliation:
Department of Biomedical Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada.
NaYoung Rho
Affiliation:
Department of Biomedical Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada.
Pavneesh Madan
Affiliation:
Department of Biomedical Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada.
Isabelle Dufort
Affiliation:
Faculté des Sciences de l'Agriculture et de l'Alimentation, Département des Sciences Animales, Pavillon INAF, Centre de Recherche en Biologie de la Reproduction (CRBR), Université Laval, Québec, Canada.
Claude Robert
Affiliation:
Faculté des Sciences de l'Agriculture et de l'Alimentation, Département des Sciences Animales, Pavillon INAF, Centre de Recherche en Biologie de la Reproduction (CRBR), Université Laval, Québec, Canada.
Laura A. Favetta
Affiliation:
Department of Biomedical Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada.
Chris Schmidt
Affiliation:
Department of Biomedical Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada.
W. Allan King*
Affiliation:
Department of Biomedical Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada.
*
All correspondence to: W. Allan King. Department of Biomedical Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada. E-mail: waking@uoguelph.ca
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Summary

Thyroid hormones (THs) have been shown to improve in vitro embryo production in cattle by increasing blastocyst formation rate, and the average cell number of blastocysts and by significantly decreasing apoptosis rate. To better understand those genetic aspects that may underlie enhanced early embryo development in the presence of THs, we characterized the bovine embryonic transcriptome at the blastocyst stage, and examined differential gene expression profiles using a bovine-specific microarray. We found that 1212 genes were differentially expressed in TH-treated embryos when compared with non-treated controls (>1.5-fold at P < 0.05). In addition 23 and eight genes were expressed uniquely in control and treated embryos, respectively. The expression of genes specifically associated with metabolism, mitochondrial function, cell differentiation and development were elevated. However, TH-related genes, including those encoding TH receptors and deiodinases, were not differentially expressed in treated embryos. Furthermore, the over-expression of 52 X-chromosome linked genes in treated embryos suggested a delay or escape from X-inactivation. This study highlights the significant impact of THs on differential gene expression in the early embryo; the identification of TH-responsive genes provides an insight into those regulatory pathways activated during development.

Keywords

BlastocystBovine embryoEmbryonic transcriptomeGene expressionThyroid hormones
Type
Research Article
Information
Zygote , Volume 24 , Issue 2 , April 2016 , pp. 266 - 276
Copyright
Copyright © Cambridge University Press 2015 

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References

Antonov, A.V., Schmidt, T., Wang, Y. & Mewes, H.W. (2008). ProfCom: A web tool for profiling the complex functionality of gene groups identified from high-throughput data. Nucleic Acids Res. 36, W347–51.CrossRefGoogle ScholarPubMed
Ashkar, F.A., Semple, E., Schmidt, C.H., St John, E., Bartlewski, P.M. & King, W.A. (2010a). Thyroid hormone supplementation improves bovine embryo development in vitro . Hum. Reprod. 25, 334–44.CrossRefGoogle ScholarPubMed
Ashkar, F.A., Bartlewski, P.M., Singh, J., Malhi, P.S., Yates, K.M., Singh, T. & King, W.A. (2010b). Thyroid hormone concentrations in systemic circulation and ovarian follicular fluid of cows. Exp. Biol. Med. 235, 215–21.CrossRefGoogle ScholarPubMed
Atkinson, B.G., Warkman, A.S. & Chen, Y. (1998). Thyroid hormone induces a reprogramming of gene expression in the liver of premetamorphic Rana catesbeiana tadpoles. Wound Repair Regen 6, 323–37.CrossRefGoogle ScholarPubMed
Avery, B., Madison, V. & Greve, T. (1991). Sex and development in bovine in-vitro fertilized embryos. Theriogenology 35, 953–63.CrossRefGoogle ScholarPubMed
Ben Hamad, M., Cornelis, F., Mbarek, H., Chabchoub, G., Marzouk, S., Bahloul, Z., Rebai, A., Fakhfakh, F., Ayadi, H., Petit-Teixeira, E. & Maalej, A. (2011). Signal transducer and activator of transcription and the risk of rheumatoid arthritis and thyroid autoimmune disorders. Clin. Exp. Rheumatol. 29, 269–74.Google ScholarPubMed
Bermejo-Alvarez, P., Rizos, D., Rath, D., Lonergan, P. & Gutierrez-Adan, A. (2010). Sex determines the expression level of one third of the actively expressed genes in bovine blastocysts. Proc. Natl. Acad. Sci. USA 107, 3394–9.CrossRefGoogle ScholarPubMed
Betts, D.H. & Madan, P. (2008). Permanent embryo arrest: molecular and cellular concepts. Mol. Hum. Reprod. 14, 445–53.CrossRefGoogle ScholarPubMed
Blazejczyk, M., Miron, M. & Nadon, R. (2007). FlexArray: a statistical data analysis software for gene expression microarrays. McGill University and Génome Québec, Innovation Centre, Montreal, Canada. Software download from http://www.gqinnovationcenter.com/services/bioinformatics/flexarray/index.aspx?l=e Google Scholar
Bousquet, D., Twagiramungu, H., Morin, N., Brisson, C., Carboneau, G. & Durocher, J. (1999). In vitro embryo production in the cow: an effective alternative to the conventional embryo production approach. Theriogenology 51, 59–70.CrossRefGoogle Scholar
Burrows, C., Abd Latip, N., Lam, S.J., Carpenter, L., Sawicka, K., Tzolovsky, G., Gabra, H., Bushell, M., Glover, D.M., Willis, A.E. & Blagden, S.P. (2010). The RNA binding protein Larp1 regulates cell division, apoptosis and cell migration. Nucleic Acids Res. 38 5542–53.CrossRefGoogle ScholarPubMed
Cagnone, G.L., Dufort, I., Vigneault, C. & Sirard, M.A. (2012). Differential gene expression profile in bovine blastocysts resulting from hyperglycemia exposure during early cleavage stages. Biol. Reprod. 86, 50.CrossRefGoogle ScholarPubMed
Camargo, L.S., Freitas, C., de Sa, W.F., de Moraes Ferreira, A., Serapiao, R.V. & Viana, J.H. (2010). Gestation length, birth weight and offspring gender ratio of in vitro-produced gyr (Bos indicus) cattle embryos. Anim. Reprod. Sci. 120, 10–15.CrossRefGoogle ScholarPubMed
Chang, E.J., Lee, S.K., Song, Y.S., Jang, Y.J., Park, H.S., Hong, J.P., Ko, A.R., Kim, D.Y., Kim, J.H., Lee, Y.J. & Heo, Y.S. (2014). IL-34 is associated with obesity, chronic inflammation, and insulin resistance. J. Clin. Endocrinol. Metab. 99, E1263–71.CrossRefGoogle ScholarPubMed
Cheng, S.Y., Leonard, J.L. & Davis, P.J. (2010). Molecular aspects of thyroid hormone actions. Endocrine Rev. 31, 139–70.CrossRefGoogle ScholarPubMed
Costa, N.N., Cordeiro, M.S., Silva, T.V., Sastre, D., Santana, P.P., Sa, A.L., Sampaio, R.V., Santos, S.S., Adona, P.R., Miranda, M.S et al. (2013). Effect of triiodothyronine on developmental competence of bovine oocytes. Theriogenology 80, 295–301.CrossRefGoogle ScholarPubMed
De La Fuente, R., Hahnel, A., Basrur, P.K. & King, W.A. (1999). X inactive-specific transcript (Xist) expression and X chromosome inactivation in the pre-attachment bovine embryos. Biol. Reprod. 60, 769–75.CrossRefGoogle Scholar
Evans, J.C., Hines, K.M., Forsythe, J.G., Erdogan, B., Shi, M., Hill, S., Rose, K.L., McLean, J.A. & Webb, D.J. (2014). Phosphorylation of serine 106 in Asef2 regulates cell migration and adhesion turnover. J. Proteome Res. 13, 3303–13.CrossRefGoogle ScholarPubMed
Favetta, L.A., Robert, C., St John, E.J., Betts, D.H. & King, W.A. (2004). P66shc, but not P53, is involved in early arrest of in vitro-produced bovine embryos. Mol. Hum. Reprod. 10, 383–92.CrossRefGoogle Scholar
Gaborit, N., Sakuma, R., Wylie, J.N., Kim, K.H., Zhang, S.S., Hui, C.C. & Bruneau, B.G. (2012). Cooperative and antagonistic roles for Irx3 and Irx5 in cardiac morphogenesis and postnatal physiology. Development 139, 4007–19.CrossRefGoogle ScholarPubMed
Gad, A., Besenfelder, U., Havlicek, V., Holker, M., Cinar, M.U., Rings, F., Dufort, I., Sirard, M.A., Schellander, K. & Tesfaye, D. (2012). In vitro culture conditions affect gene expression pattern of bovine blastocyst in a stage-specific manner. Reprod. Fertil. Dev. 25, 254.Google Scholar
Gavriouchkina, D., Fischer, S., Ivacevic, T., Stolte, J., Benes, V. & Dekens, M.P. (2010). Thyrotroph embryonic factor regulates light-induced transcription of repair genes in zebrafish embryonic cells. PLoS One 5, e12542.CrossRefGoogle ScholarPubMed
Goossens, K., De Spiegelaere, W., Stevens, M., Burvenich, C., De Spiegeleer, B., Cornillie, P., Van Zeveren, A., Van Soom, A. & Peelman, L. (2012). Differential microRNA expression analysis in blastocysts by whole mount in situ hybridization and reverse transcription quantitative polymerase chain reaction on laser capture microdissection samples. Anal. Biochem. 423, 93–101.CrossRefGoogle ScholarPubMed
Goossens, K., Van Poucke, M., Van Soom, A., Vandesompele, J., Van Zeveren, A. & Peelman, L.J. (2005). Selection of reference genes for quantitative real-time PCR in bovine preimplantation embryos. BMC Dev. Biol. 5, 27.CrossRefGoogle ScholarPubMed
Goossens, K., Van Soom, A., Van Poucke, M., Vandaele, L., Vandesompele, J., Van Zeveren, A. & Peelman, L.J. (2007). Identification and expression analysis of genes associated with bovine blastocyst formation. BMC Dev. Biol. 7, 64.CrossRefGoogle ScholarPubMed
Hamilton, C.K., Combe, A., Caudle, J., Ashkar, F.A., Macaulay, A.D., Blondin, P. & King, W.A. (2012). A novel approach to sexing bovine blastocysts using male-specific gene expression. Theriogenology 77, 1587–96.CrossRefGoogle ScholarPubMed
Harper, M.E. & Seifert, E.L. (2008). Thyroid hormone effects on mitochondrial energetics. Thyroid 18, 145–56.CrossRefGoogle ScholarPubMed
Jaroudi, S. & SenGupta, S. (2007). DNA repair in mammalian embryos. Mutat. Res. 635, 53–77.CrossRefGoogle ScholarPubMed
Jaroudi, S., Kakourou, G., Cawood, S., Doshi, A., Ranieri, D.M., Serhal, P., Harper, J.C. & SenGupta, S.B. (2009). Expression profiling of DNA repair genes in human oocytes and blastocysts using microarrays. Hum. Reprod. 24, 2649–55.CrossRefGoogle ScholarPubMed
Jeseta, M., Ctvrtlikova Knitlova, D., Hanzalova, K., Hulinska, P., Hanulakova, S., Milakovic, I., Nemcova, L., Kanka, J. & Machatkova, M. (2014). Mitochondrial patterns in bovine oocytes with different meiotic competence related to their in vitro maturation. Reprod. Domest. Anim. 49, 469–75.CrossRefGoogle ScholarPubMed
King, W.A. (2008). Chromosome variation in the embryos of domestic animals. Cytogenet. Genome Res. 120, 81–90.CrossRefGoogle ScholarPubMed
King, W.A., Coppola, G., Alexander, B., Mastromonaco, G., Perrault, S., Nino-Soto, M.I., Pinton, A., Joudrey, E.M. & Betts, D.H. (2006). The impact of chromosomal alteration on embryo development. Theriogenology 65, 166–77.CrossRefGoogle ScholarPubMed
Kochhar, H.P., Peippo, J. & King, W.A. (2001). Sex related embryo development. Theriogenology 55, 3–14.CrossRefGoogle ScholarPubMed
Lane, M. & Gardner, D.K. (2007). Embryo culture medium: which is the best? Best Pract. Res. Clin. Obstet. Gynaecol 21, 83–100.CrossRefGoogle ScholarPubMed
Lazar, M.A 1993 Thyroid hormone receptors: multiple forms, multiple possibilities. Endocrine Rev 14, 184–93.Google ScholarPubMed
Macaulay, A.D., Hamilton, C.K., King, W.A. & Bartlewski, P.M. (2013). Influence of physiological concentrations of androgens on the developmental competence and sex ratio of in vitro produced bovine embryos. Reprod. Biol. 13, 41–50.CrossRefGoogle ScholarPubMed
Masteller, E.L. & Wong, B.R. (2014). Targeting IL-34 in chronic inflammation. Drug Discov. Today 19, 1212–16.CrossRefGoogle ScholarPubMed
Mastromonaco, G.F., Favetta, L.A., Smith, L.C., Filion, F. & King, W.A. (2007). The influence of nuclear content on developmental competence of gaur × cattle hybrid in vitro fertilized and somatic cell nuclear transfer embryos. Biol. Reprod. 76, 514–23.CrossRefGoogle ScholarPubMed
McPherson, N.O., Zander-Fox, D. & Lane, M. (2014). Stimulation of mitochondrial embryo metabolism by dichloroacetic acid in an aged mouse model improves embryo development and viability. Fertil. Steril. 101, 1458–66.CrossRefGoogle Scholar
Memili, E. & First, N.L. (2000). Zygotic and embryonic gene expression in cow: A review of timing and mechanisms of early gene expression as compared with other species. Zygote 8, 87–96.CrossRefGoogle ScholarPubMed
Menezo, Y., Dale, B. & Cohen, M. (2010). DNA damage and repair in human oocytes and embryos: A review. Zygote 18, 357–65.CrossRefGoogle ScholarPubMed
Milki, A.A., Jun, S.H., Hinckley, M.D., Westphal, L.W., Giudice, L.C. & Behr, B. (2003). Comparison of the sex ratio with blastocyst transfer and cleavage stage transfer. J. Assist. Reprod. Genet. 20, 323–6.CrossRefGoogle ScholarPubMed
Morvan-Dubois, G., Fini, J.B. & Demeneix, B.A. (2013). Is thyroid hormone signaling relevant for vertebrate embryogenesis? Curr. Topics Dev. Biol. 103, 365–96.CrossRefGoogle ScholarPubMed
Mtango, N.R., Harvey, A.J., Latham, K.E. & Brenner, C.A. (2008). Molecular control of mitochondrial function in developing rhesus monkey oocytes and preimplantation-stage embryos. Reprod. Fertil. Dev. 20, 846–59.CrossRefGoogle ScholarPubMed
Nagai, S., Mabuchi, T., Hirata, S., Shoda, T., Kasai, T., Yokota, S., Shitara, H., Yonekawa, H. & Hoshi, K. (2006). Correlation of abnormal mitochondrial distribution in mouse oocytes with reduced developmental competence. Tohoku J. Exp Med. 210, 137–44.CrossRefGoogle ScholarPubMed
Nagano, M., Katagiri, S. & Takahashi, Y. (2006). ATP content and maturational/developmental ability of bovine oocytes with various cytoplasmic morphologies. Zygote 14, 299–304.CrossRefGoogle ScholarPubMed
Nakamura, T.Y., Jeromin, A., Mikoshiba, K. & Wakabayashi, S. (2011). Neuronal calcium sensor-1 promotes immature heart function and hypertrophy by enhancing Ca2+ signals. Circ. Res. 109, 512–23.CrossRefGoogle ScholarPubMed
Oetting, A. & Yen, P.M. (2007). New insights into thyroid hormone action. Best Pract. Res. Clin. Endocrinol. Metab. 21, 193–208.CrossRefGoogle ScholarPubMed
Peippo, J., Farazmand, A., Kurkilahti, M., Markkula, M., Basrur, P.K. & King, W.A. (2002). Sex-chromosome linked gene expression in in-vitro produced bovine embryos. Mol. Hum. Reprod. 8, 923–9.CrossRefGoogle ScholarPubMed
Pelayo, S., Oliveira, E., Thienpont, B., Babin, P.J., Raldua, D., Andre, M. & Pina, B. (2012). Triiodothyronine-induced changes in the zebrafish transcriptome during the eleutheroembryonic stage: Implications for bisphenol A developmental toxicity. Aquat. Toxicol. 110–111, 114–22.CrossRefGoogle ScholarPubMed
Plante, L., Plante, C., Shepherd, D.L. & King, W.A. (1994). Cleavage and 3H-uridine incorporation in bovine embryos of high in vitro developmental potential. Mol. Reprod. Dev. 39, 375–383.CrossRefGoogle ScholarPubMed
Power, D.M., Llewellyn, L., Faustino, M., Nowell, MA., Bjornsson, B.T., Einarsdottir, IE., Canario, A.V. & Sweeney, G.E. (2001). Thyroid hormones in growth and development of fish. Comp. Biochem. Physiol. Toxicol. Pharmacol. CBP 130, 447–459.CrossRefGoogle ScholarPubMed
Ramakers, C., Ruijter, J.M., Deprez, R.H. & Moorman, A.F. (2003). Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neurosci. Lett. (2003). 339, 62–6.CrossRefGoogle ScholarPubMed
Robert, C., McGraw, S., Massicotte, L., Pravetoni, M., Gandolfi, F. & Sirard, M.A. (2002). Quantification of housekeeping transcript levels during the development of bovine preimplantation embryos. Biol. Reprod. 67, 1465–72.CrossRefGoogle ScholarPubMed
Robert, C., Nieminen, J., Dufort, I., Gagne, D., Grant, J.R., Cagnone, G., Plourde, D., Nivet, A.T., Fournier, E., Paquet, E. et al. (2011). Combining resources to obtain a comprehensive survey of the bovine embryo transcriptome through deep sequencing and microarrays. Mol. Reprod. Dev. 78, 651–64.CrossRefGoogle ScholarPubMed
Sanchez-Aguilera, A., Rattmann, I., Drew, D.Z., Müller, L.U., Summey, V., Lucas, D.M., Byrd, J.C., Croce, C.M., Gu, Y., Cancelas, J.A., Johnston, P., Moritz, T. & Williams, D.A. (2010). Involvement of RhoH GTPase in the development of B-cell chronic lymphocytic leukemia. Leukemia 24, 97–104.CrossRefGoogle ScholarPubMed
Sheehan, T.E., Kumar, P.A. & Hood, D.A. (2004). Tissue-specific regulation of cytochrome c oxidase subunit expression by thyroid hormone. Am. J. Physiol. Endocrinol. Metab. 286, E968–74.CrossRefGoogle ScholarPubMed
Stojkovic, M., Machado, SA., Stojkovic, P., Zakhartchenko, V., Hutzler, P., Goncalves, P.B. & Wolf, E. (2001). Mitochondrial distribution and adenosine triphosphate content of bovine oocytes before and after in vitro maturation: Correlation with morphological criteria and developmental capacity after in vitro fertilization and culture. Biol. Reprod. 64, 904–9.CrossRefGoogle ScholarPubMed
Sylvestre, E.L., Robert, C., Pennetier, S., Labrecque, R., Gilbert, I., Dufort, I., Léveillé, M.C. & Sirard, M.A. (2013). Evolutionary conservation of the oocyte transcriptome among vertebrates and its implications for understanding human reproductive function. Mol. Hum. Reprod. 19, 369–79.CrossRefGoogle ScholarPubMed
Tarazona, A.M., Rodriguez, J.I., Restrepo, L.F. & Olivera-Angel, M. (2006). Mitochondrial activity, distribution and segregation in bovine oocytes and in embryos produced in vitro . Reprod. Domest. Anim. 41, 5–11.CrossRefGoogle ScholarPubMed
Troeger, A. & Williams, D.A. (2013). Hematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders. Exp. Cell Res. 319, 2375–83.CrossRefGoogle ScholarPubMed
Troeger, A., Chae, H.D., Senturk, M., Wood, J. & Williams, D.A. (2013). A unique carboxyl-terminal insert domain in the hematopoietic-specific, GTPase-deficient Rho GTPase RhoH regulates post-translational processing. J. Biol. Chem. 288, 36451–62.CrossRefGoogle ScholarPubMed
Troeger, A., Johnson, A.J., Wood, J., Blum, W.G., Andritsos, L.A., Byrd, J.C. & Williams, D.A. (2012). RhoH is critical for cell-microenvironment interactions in chronic lymphocytic leukemia in mice and humans. Blood 119, 4708–18.CrossRefGoogle ScholarPubMed
Van Blerkom, J. (2011). Mitochondrial function in the human oocyte and embryo and their role in developmental competence. Mitochondrion 11, 797–813.CrossRefGoogle ScholarPubMed
Van Blerkom, J. (2009). Mitochondria in early mammalian development. Semin. Cell. Dev. Biol. 20, 354–64.CrossRefGoogle ScholarPubMed
Wu, Y. & Koenig, R.J. (2000). Gene regulation by thyroid hormone. Trends Endocrinol. Metab. TEM 11, 207–11.CrossRefGoogle ScholarPubMed
Xu, K.P., Yadav, B.R., King, W.A. & Betteridge, K.J. (1992). Sex-related differences in developmental rates of bovine embryos produced and cultured in vitro. Mol. Reprod. Dev. 31, 249–52.CrossRefGoogle ScholarPubMed
Yan, N., Meng, S., Zhou, J., Xu, J., Muhali, F.S., Jiang, W., Shi, L., Shi, X. & Zhang, J. (2014). Association between STAT4 gene polymorphisms and autoimmune thyroid diseases in a Chinese population. Int. J. Mol. Sci. 15, 12280–93.CrossRefGoogle ScholarPubMed
Yen, P.H., Ellison, J., Salido, E.C., Mohandas, T. & Shapiro, L. (1992). Isolation of a new gene from the distal short arm of the human X chromosome that escapes X-inactivation. Hum. Mol. Genet. 1, 47–52.CrossRefGoogle ScholarPubMed
Yen, P.M., Ando, S., Feng, X., Liu, Y., Maruvada, P. & Xia, X. (2006). Thyroid hormone action at the cellular, genomic and target gene levels. Mol. Cell. Endocrinol. 246, 121–7.CrossRefGoogle ScholarPubMed
Yip, P.K., Wong, L.F., Sears, T.A., Yáñez-Muñoz, R.J. & McMahon, S.B. (2010). Cortical overexpression of neuronal calcium sensor-1 induces functional plasticity in spinal cord following unilateral pyramidal tract injury in rat. PLoS Biol. 8, e1000399.CrossRefGoogle ScholarPubMed
Yoshida, K. & Miki, Y. (2004). Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage. Cancer Sci. 95, 866–71.CrossRefGoogle ScholarPubMed
You, J., Wang, L., Huang, J., Jiang, M., Chen, Q., Wang, Y. & Jiang, Z. (2015). Low glucose transporter SLC2A5-inhibited human normal adjacent lung adenocarcinoma cytoplasmic pro-B cell development mechanism network. Mol. Cell. Biochem. 399 (1–2), 71–6.CrossRefGoogle ScholarPubMed
Zhang, B., Kirov, S. & Snoddy, J. (2005). WebGestalt: an integrated system for exploring gene sets in various biological contexts. Nucleic Acids Res. 33, W741–8.CrossRefGoogle ScholarPubMed
Zhang, J. & Lazar, M.A. (2000). The mechanism of action of thyroid hormones. Ann. Rev. Physiol. 62, 439–66.CrossRefGoogle ScholarPubMed
Zhang, S.S., Carrillo, A.J. & Darling, D.S. (1997). Expression of multiple thyroid hormone receptor mRNAs in human oocytes, cumulus cells, and granulosa cells. Mol. Hum. Reprod. 3, 555–62.CrossRefGoogle ScholarPubMed