Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Cholesterol metabolism in rabbit blastocysts under maternal diabetes

S. Mareike Pendzialek A C * , Maria Schindler A * , Torsten Plösch B , Jacqueline Gürke A , Elisa Haucke A , Stefanie Hecht A , Bernd Fischer A and Anne Navarrete Santos A
+ Author Affiliations
- Author Affiliations

A Department of Anatomy and Cell Biology, Martin Luther University Faculty of Medicine, Grosse Steinstr. 52, 06108 Halle (Saale), Germany.

B Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 Groningen, The Netherlands.

C Corresponding author. Email: mareike.pendzialek@medizin.uni-halle.de

Reproduction, Fertility and Development - https://doi.org/10.1071/RD15542
Submitted: 23 December 2015  Accepted: 24 October 2016   Published online: 6 December 2016

Abstract

In the rabbit reproductive model, maternal experimentally induced insulin-dependent diabetes mellitus (expIDD) leads to accumulation of lipid droplets in blastocysts. Cholesterol metabolism is a likely candidate to explain such metabolic changes. Therefore, in the present study we analysed maternal and embryonic cholesterol concentrations and expression of related genes in vivo (diabetic model) and in vitro (embryo culture in hyperglycaemic medium). In pregnant expIDD rabbits, the serum composition of lipoprotein subfractions was changed, with a decrease in high-density lipoprotein cholesterol and an increase in very low-density lipoprotein cholesterol; in uterine fluid, total cholesterol concentrations were elevated. Expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), very low-density lipoprotein receptor (VLDLR), sterol regulatory element binding transcription factor 2 (SREBF2), insulin-induced gene-1 (INSIG1) and cholesterol 7α-hydroxylase (CYP7A1) mRNA was decreased in the liver and low-density lipoprotein receptor (LDLR) mRNA expression was decreased in the adipose tissue of diabetic rabbits. In embryos from diabetic rabbits, the mean (± s.e.m.) ratio of cholesterol concentrations in trophoblasts to embryoblasts was changed from 1.27 ± 2.34 (control) to 0.88 ± 3.85 (expIDD). Rabbit blastocysts expressed HMGCR, LDLR, VLDLR, SREBF2 and INSIG1 but not CYP7A1, without any impairment of expression as a result of maternal diabetes. In vitro hyperglycaemia decreased embryonic HMGCR and SREBF2 transcription in rabbit blastocysts. The findings of the present study show that a diabetic pregnancy leads to distinct changes in maternal cholesterol metabolism with a minor effect on embryo cholesterol metabolism.

Additional keywords: development, embryo, lipid, pregnancy, preimplantation.


References

Åman, J., Hansson, U., Östlund, I., Wall, K., and Persson, B. (2011). Increased fat mass and cardiac septal hypertrophy in newborn infants of mothers with well-controlled diabetes during pregnancy. Neonatology 100, 147–154.
Increased fat mass and cardiac septal hypertrophy in newborn infants of mothers with well-controlled diabetes during pregnancy.CrossRef | open url image1

Arnold, S. J., Stappert, J., Bauer, A., Kispert, A., Herrmann, B. G., and Kemler, R. (2000). Brachyury is a target gene of the Wnt/beta-catenin signaling pathway. Mech. Dev. 91, 249–258.
Brachyury is a target gene of the Wnt/beta-catenin signaling pathway.CrossRef | 1:CAS:528:DC%2BD3cXhsVagsbY%3D&md5=d2a80c6e18f4bd4d6bdbee55dfc90c12CAS | open url image1

Baardman, M. E., Erwich, J. J. H. M., Berger, R. M. F., Hofstra, R. M. W., Kerstjens-Frederikse, W. S., Lütjohann, D., and Plösch, T. (2012). The origin of fetal sterols in second-trimester amniotic fluid: endogenous synthesis or maternal–fetal transport? Am. J. Obstet. Gynecol. 207, 202.e19–202.e25.
The origin of fetal sterols in second-trimester amniotic fluid: endogenous synthesis or maternal–fetal transport?CrossRef | 1:CAS:528:DC%2BC38XptFaisLc%3D&md5=b4086bfa0b52d5c2161b7dfa25e4e319CAS | open url image1

Belknap, W. M., and Dietschy, J. M. (1988). Sterol synthesis and low density lipoprotein clearance in vivo in the pregnant rat, placenta, and fetus. Sources for tissue cholesterol during fetal development. J. Clin. Invest. 82, 2077–2085.
Sterol synthesis and low density lipoprotein clearance in vivo in the pregnant rat, placenta, and fetus. Sources for tissue cholesterol during fetal development.CrossRef | 1:CAS:528:DyaL1MXjslWhtQ%3D%3D&md5=0796428cf14cafb9df15daaa91c7bf83CAS | open url image1

Bligh, E. G., and Dyer, W. J. (1959). A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 37, 911–917.
A rapid method of total lipid extraction and purification.CrossRef | 1:CAS:528:DyaG1MXhtVSgt70%3D&md5=620648fe66a0f5e25cc44bff962b2a43CAS | open url image1

Butte, N. F. (2000). Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus. Am. J. Clin. Nutr. 71, 1256S–1261S.
| 1:CAS:528:DC%2BD3cXivFymtbs%3D&md5=247f01e6104828734160f9995b2e6094CAS | open url image1

Christiansen-Weber, T. A., Voland, J. R., Wu, Y., Ngo, K., Roland, B. L., Nguyen, S., Peterson, P. A., and Fung-Leung, W.-P. (2000). Functional loss of ABCA1 in mice causes severe placental malformation, aberrant lipid distribution, and kidney glomerulonephritis as well as high-density lipoprotein cholesterol deficiency. Am. J. Pathol. 157, 1017–1029.
Functional loss of ABCA1 in mice causes severe placental malformation, aberrant lipid distribution, and kidney glomerulonephritis as well as high-density lipoprotein cholesterol deficiency.CrossRef | 1:CAS:528:DC%2BD3cXmvFWqtbs%3D&md5=612149776cdfcd3c19ea3a4e308738edCAS | open url image1

Devery, R. A., O’Meara, N., Collins, P. B., Johnson, A. H., Scott, L., and Tomkin, G. H. (1987). A comparative study of the rate-limiting enzymes of cholesterol synthesis, esterification and catabolism in the alloxan-induced diabetic rat and rabbit. Comp. Biochem. Physiol. B 88, 547–550.
A comparative study of the rate-limiting enzymes of cholesterol synthesis, esterification and catabolism in the alloxan-induced diabetic rat and rabbit.CrossRef | 1:STN:280:DyaL1c7htVCnsQ%3D%3D&md5=d8325db91ea2c8d350fcf58bfef8dc1eCAS | open url image1

Evers, I. M., De Valk, H. W., Mol, B. W. J., Ter Braak, E. W. M. T., and Visser, G. H. A. (2002). Macrosomia despite good glycaemic control in Type I diabetic pregnancy; results of a nationwide study in The Netherlands. Diabetologia 45, 1484–1489.
Macrosomia despite good glycaemic control in Type I diabetic pregnancy; results of a nationwide study in The Netherlands.CrossRef | 1:CAS:528:DC%2BD38XoslOrs78%3D&md5=edda29bc0a4d33ee4477ff3d6b23833aCAS | open url image1

Farese, R. V., and Herz, J. (1998). Cholesterol metabolism and embryogenesis. Trends Genet. 14, 115–120.
Cholesterol metabolism and embryogenesis.CrossRef | 1:CAS:528:DyaK1cXhvFWkur4%3D&md5=4860b8a7eb6b9e70a0e803a12da8f052CAS | open url image1

Fischer, B., Chavatte-Palmer, P., Viebahn, C., Navarrete Santos, A., and Duranthon, V. (2012). Rabbit as a reproductive model for human health. Reproduction 144, 1–10.
Rabbit as a reproductive model for human health.CrossRef | 1:CAS:528:DC%2BC38XhtV2ht7rK&md5=81aff50416a8c87485141c935745fdfaCAS | open url image1

Fujimoto, V. Y., Kane, J. P., Ishida, B. Y., Bloom, M. S., and Browne, R. W. (2010). High-density lipoprotein metabolism and the human embryo. Hum. Reprod. Update 16, 20–38.
High-density lipoprotein metabolism and the human embryo.CrossRef | 1:CAS:528:DC%2BD1MXhsFOht7rI&md5=0c221174d6b9fcc22499a0c06b430057CAS | open url image1

Goldstein, J. L., DeBose-Boyd, R. A., and Brown, M. S. (2006). Protein sensors for membrane sterols. Cell 124, 35–46.
Protein sensors for membrane sterols.CrossRef | 1:CAS:528:DC%2BD28XntVGlug%3D%3D&md5=4f8fe9e11deb737f844ca675e73b3460CAS | open url image1

Gürke, J., Schindler, M., Pendzialek, S. M., Thieme, R., Grybel, K. J., Heller, R., Spengler, K., Fleming, T. P., Fischer, B., and Navarrete Santos, A. (2016). Maternal diabetes promotes mTORC1 downstream signalling in rabbit preimplantation embryos. Reproduction 151, 465–476.
Maternal diabetes promotes mTORC1 downstream signalling in rabbit preimplantation embryos.CrossRef | open url image1

Horton, J. D., Goldstein, J. L., and Brown, M. S. (2002). SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J. Clin. Invest. 109, 1125–1131.
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver.CrossRef | 1:CAS:528:DC%2BD38XjsFals7c%3D&md5=f4ea27fdc79563dd073bb37d992f4a95CAS | open url image1

Houghton, F. D. (2006). Energy metabolism of the inner cell mass and trophectoderm of the mouse blastocyst. Differentiation 74, 11–18.
Energy metabolism of the inner cell mass and trophectoderm of the mouse blastocyst.CrossRef | 1:CAS:528:DC%2BD28XjtVeks78%3D&md5=f702e0b6fb752b10dbf2af9febbc9aa1CAS | open url image1

Iwasaki, T., Takahashi, S., Takahashi, M., Zenimaru, Y., Kujiraoka, T., Ishihara, M., Nagano, M., Suzuki, J., Miyamori, I., Naiki, H., Sakai, J., Fujino, T., Miller, N. E., Yamamoto, T. T., and Hattori, H. (2005). Deficiency of the very low-density lipoprotein (VLDL) receptors in streptozotocin-induced diabetic rats: insulin dependency of the VLDL receptor. Endocrinology 146, 3286–3294.
Deficiency of the very low-density lipoprotein (VLDL) receptors in streptozotocin-induced diabetic rats: insulin dependency of the VLDL receptor.CrossRef | 1:CAS:528:DC%2BD2MXntVaitLo%3D&md5=88ee8e714dbbf032241587182604af20CAS | open url image1

Janowski, B. A. (2002). The hypocholesterolemic agent LY295427 up-regulates INSIG-1, identifying the INSIG-1 protein as a mediator of cholesterol homeostasis through SREBP. Proc. Natl Acad. Sci. USA 99, 12 675–12 680.
The hypocholesterolemic agent LY295427 up-regulates INSIG-1, identifying the INSIG-1 protein as a mediator of cholesterol homeostasis through SREBP.CrossRef | 1:CAS:528:DC%2BD38XnvFGhsrc%3D&md5=906982f10cd7223083bcf67a080fba91CAS | open url image1

Kilby, M. D., Neary, R. H., Mackness, M. I., and Durrington, P. N. (1998). Fetal and maternal lipoprotein metabolism in human pregnancy complicated by type I diabetes mellitus. J. Clin. Endocrinol. Metab. 83, 1736–1741.
| 1:CAS:528:DyaK1cXjtF2gs7c%3D&md5=28be7650415b41c0cf35fe28d7afa1e8CAS | open url image1

Königsdorf, C. A. I., Navarrete Santos, A., Schmidt, J.-S., Fischer, S., and Fischer, B. (2012). Expression profile of fatty acid metabolism genes in preimplantation blastocysts of obese and non-obese mice. Obes. Facts 5, 575–586.
Expression profile of fatty acid metabolism genes in preimplantation blastocysts of obese and non-obese mice.CrossRef | open url image1

Kwong, W. Y., Wild, A. E., Roberts, P., Willis, A. C., and Fleming, T. P. (2000). Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Development 127, 4195–4202.
| 1:CAS:528:DC%2BD3cXotVWisbw%3D&md5=549c53b3d6bfc8281620bf04d48948b5CAS | open url image1

Leese, H. J., Sturmey, R. G., Baumann, C. G., and McEvoy, T. G. (2007). Embryo viability and metabolism: obeying the quiet rules. Hum. Reprod. 22, 3047–3050.
Embryo viability and metabolism: obeying the quiet rules.CrossRef | open url image1

Leese, H. J., Baumann, C. G., Brison, D. R., McEvoy, T. G., and Sturmey, R. G. (2008). Metabolism of the viable mammalian embryo: quietness revisited. Mol. Hum. Reprod. 14, 667–672.
Metabolism of the viable mammalian embryo: quietness revisited.CrossRef | 1:CAS:528:DC%2BD1MXltV2gsA%3D%3D&md5=80f6db2afafa8040cce9666a18fba40cCAS | open url image1

Lepercq, J., Taupin, P., Dubois-Laforgue, D., Duranteau, L., Lahlou, N., Boitard, C., Landais, P., Hauguel-De Mouzon, S., and Timsit, J. (2001). Heterogeneity of fetal growth in type 1 diabetic pregnancy. Diabetes Metab. 27, 339–344.
| 1:STN:280:DC%2BD3MznsVGqsA%3D%3D&md5=02a11fbdb0c43272a0453fdfad8233a4CAS | open url image1

Loewen, N., Chen, J., Dudley, V. J., Sarthy, V. P., and Mathura, J. R. (2009). Genomic response of hypoxic Müller cells involves the very low density lipoprotein receptor as part of an angiogenic network. Exp. Eye Res. 88, 928–937.
Genomic response of hypoxic Müller cells involves the very low density lipoprotein receptor as part of an angiogenic network.CrossRef | 1:CAS:528:DC%2BD1MXltVymsL8%3D&md5=23df8ee36c09151b5a5bc705f9cef690CAS | open url image1

Martí, E., and Bovolenta, P. (2002). Sonic hedgehog in CNS development: one signal, multiple outputs. Trends Neurosci. 25, 89–96.
Sonic hedgehog in CNS development: one signal, multiple outputs.CrossRef | open url image1

Maurer, R. R. (1978). Advances in rabbit embryo culture. In ‘Methods in Mammalian Reproduction’. (Ed. J. C. Daniel Jr.) pp. 259–272. (Academic Press: New York, NY.)

Merzouk, H., Bouchenak, M., Loukidi, B., Madani, S., Prost, J., and Belleville, J. (2000). Fetal macrosomia related to maternal poorly controlled type 1 diabetes strongly impairs serum lipoprotein concentrations and composition. J. Clin. Pathol. 53, 917–923.
Fetal macrosomia related to maternal poorly controlled type 1 diabetes strongly impairs serum lipoprotein concentrations and composition.CrossRef | 1:STN:280:DC%2BD3M7msFOmtQ%3D%3D&md5=84e4e18fdebe0b62d013122b084a9c8cCAS | open url image1

Montoudis, A., Simoneau, L., Brissette, L., Forest, J. C., Savard, R., and Lafond, J. (1999). Impact of a cholesterol enriched diet on maternal and fetal plasma lipids and fetal deposition in pregnant rabbits. Life Sci. 64, 2439–2450.
Impact of a cholesterol enriched diet on maternal and fetal plasma lipids and fetal deposition in pregnant rabbits.CrossRef | 1:CAS:528:DyaK1MXjslGjtL0%3D&md5=221cd195741acbeb8b1ca0671a54d79bCAS | open url image1

Napoli, C., D’Armiento, F. P., Mancini, F. P., Postiglione, A., Witztum, J. L., Palumbo, G., and Palinski, W. (1997). Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J. Clin. Invest. 100, 2680–2690.
Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions.CrossRef | 1:CAS:528:DyaK2sXotVaktLo%3D&md5=36828f950486b23501beeca87a935081CAS | open url image1

Navarrete Santos, A., Körber, S., Küllertz, G., Fischer, G., and Fischer, B. (2000). Oxygen stress increases prolyl cis/trans isomerase activity and expression of cyclophilin 18 in rabbit blastocysts. Biol. Reprod. 62, 1–7.
Oxygen stress increases prolyl cis/trans isomerase activity and expression of cyclophilin 18 in rabbit blastocysts.CrossRef | open url image1

Ness, G. C., Zhao, Z., and Wiggins, L. (1994). Insulin and glucagon modulate hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity by affecting immunoreactive protein levels. J. Biol. Chem. 269, 29168–29172.
| 1:CAS:528:DyaK2cXmsVKrsrY%3D&md5=e67cc937c8f91d7d878474dc0664e056CAS | open url image1

Newnham, J. P., Moss, T. J., Nitsos, I., Sloboda, D. M., and Challis, J. R. (2002). Nutrition and the early origins of adult disease. Asia Pac. J. Clin. Nutr. 11, S537–S542.
Nutrition and the early origins of adult disease.CrossRef | open url image1

Nijstad, N., Wiersma, H., Gautier, T., Van der Giet, M., Maugeais, C., and Tietge, U. J. F. (2009). Scavenger receptor BI-mediated selective uptake is required for the remodeling of high density lipoprotein by endothelial lipase. J. Biol. Chem. 284, 6093–6100.
Scavenger receptor BI-mediated selective uptake is required for the remodeling of high density lipoprotein by endothelial lipase.CrossRef | 1:CAS:528:DC%2BD1MXisVSksbs%3D&md5=800aec313e258bf6c31a7cb301ecc075CAS | open url image1

Nowaczyk, M. J., Farrell, S. A., Sirkin, W. L., Velsher, L., Krakowiak, P. A., Waye, J. S., and Porter, F. D. (2001). Smith–Lemli–Opitz (RHS) syndrome: holoprosencephaly and homozygous IVS8–1G→C genotype. Am. J. Med. Genet. 103, 75–80.
Smith–Lemli–Opitz (RHS) syndrome: holoprosencephaly and homozygous IVS8–1G→C genotype.CrossRef | 1:STN:280:DC%2BD3MrhtlKntQ%3D%3D&md5=512f8f8bc4b7fb233d8fe7aa006a4fc1CAS | open url image1

Ohashi, K., Osuga, J., Tozawa, R., Kitamine, T., Yagyu, H., Sekiya, M., Tomita, S., Okazaki, H., Tamura, Y., Yahagi, N., Iizuka, Y., Harada, K., Gotoda, T., Shimano, H., Yamada, N., and Ishibashi, S. (2003). Early embryonic lethality caused by targeted disruption of the 3-hydroxy-3-methylglutaryl-CoA reductase gene. J. Biol. Chem. 278, 42 936–42 941.
Early embryonic lethality caused by targeted disruption of the 3-hydroxy-3-methylglutaryl-CoA reductase gene.CrossRef | 1:CAS:528:DC%2BD3sXosFSkt70%3D&md5=4ccb7b492138eb8a11fa39a1d02a4eddCAS | open url image1

Palinski, W., and Napoli, C. (2002). The fetal origins of atherosclerosis: maternal hypercholesterolemia, and cholesterol-lowering or antioxidant treatment during pregnancy influence in utero programming and postnatal susceptibility to atherogenesis. FASEB J. 16, 1348–1360.
The fetal origins of atherosclerosis: maternal hypercholesterolemia, and cholesterol-lowering or antioxidant treatment during pregnancy influence in utero programming and postnatal susceptibility to atherogenesis.CrossRef | 1:CAS:528:DC%2BD38XntFWmt7s%3D&md5=54299767b69261d62833c45fdb224c86CAS | open url image1

Plagemann, A. (2011). Maternal diabetes and perinatal programming. Early Hum. Dev. 87, 743–747.
Maternal diabetes and perinatal programming.CrossRef | 1:STN:280:DC%2BC3MbkvFWhsw%3D%3D&md5=73dca21546e3f7ce7781b32e27cd993eCAS | open url image1

Portilho, D. M., Martins, E. R., Costa, M. L., and Mermelstein, C. S. (2007). A soluble and active form of Wnt-3a protein is involved in myogenic differentiation after cholesterol depletion. FEBS Lett. 581, 5787–5795.
A soluble and active form of Wnt-3a protein is involved in myogenic differentiation after cholesterol depletion.CrossRef | 1:CAS:528:DC%2BD2sXhsVChu7fN&md5=afe1f570241ac7a6bd8cf3b160f75a2bCAS | open url image1

Pratt, H. P., Keith, J., and Chakraborty, J. (1980). Membrane sterols and the development of the preimplantation mouse embryo. J. Embryol. Exp. Morphol. 60, 303–319.
| 1:CAS:528:DyaL3MXotFSrug%3D%3D&md5=6d5fe0454edc190c5a8942d8144ec400CAS | open url image1

Ramin, N., Thieme, R., Fischer, S., Schindler, M., Schmidt, T., Fischer, B., and Navarrete Santos, A. (2010). Maternal diabetes impairs gastrulation and insulin and IGF-I receptor expression in rabbit blastocysts. Endocrinology 151, 4158–4167.
Maternal diabetes impairs gastrulation and insulin and IGF-I receptor expression in rabbit blastocysts.CrossRef | 1:CAS:528:DC%2BC3cXhtF2qtrzO&md5=cbc0657eaa09571074e363407bc486d6CAS | open url image1

Sato, N., Kawamura, K., Fukuda, J., Honda, Y., Sato, T., Tanikawa, H., Kodama, H., and Tanaka, T. (2003). Expression of LDL receptor and uptake of LDL in mouse preimplantation embryos. Mol. Cell. Endocrinol. 202, 191–194.
Expression of LDL receptor and uptake of LDL in mouse preimplantation embryos.CrossRef | 1:CAS:528:DC%2BD3sXktFSntr0%3D&md5=13ac260ec105d342f851c0ad53fa7653CAS | open url image1

Schaefer-Graf, U. M., Graf, K., Kulbacka, I., Kjos, S. L., Dudenhausen, J., Vetter, K., and Herrera, E. (2008). Maternal lipids as strong determinants of fetal environment and growth in pregnancies with gestational diabetes mellitus. Diabetes Care 31, 1858–1863.
Maternal lipids as strong determinants of fetal environment and growth in pregnancies with gestational diabetes mellitus.CrossRef | open url image1

Schindler, M., Fischer, S., Thieme, R., Fischer, B., and Santos, A. N. (2013). cAMP-responsive element binding protein: a vital link in embryonic hormonal adaptation. Endocrinology 154, 2208–2221.
cAMP-responsive element binding protein: a vital link in embryonic hormonal adaptation.CrossRef | 1:CAS:528:DC%2BC3sXotl2hurs%3D&md5=e2cb85899b5b52d8203dcdcca5bcdfd7CAS | open url image1

Schindler, M., Pendzialek, M., Navarrete Santos, A., Plösch, T., Seyring, S., Gürke, J., Haucke, E., Knelangen, J. M., Fischer, B., and Santos, A. N. (2014). Maternal diabetes leads to unphysiological high lipid accumulation in rabbit preimplantation embryos. Endocrinology 155, 1498–1509.
Maternal diabetes leads to unphysiological high lipid accumulation in rabbit preimplantation embryos.CrossRef | open url image1

Sewell, M. F., Huston-Presley, L., Super, D. M., and Catalano, P. (2006). Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am. J. Obstet. Gynecol. 195, 1100–1103.
Increased neonatal fat mass, not lean body mass, is associated with maternal obesity.CrossRef | open url image1

Shakib, K., Norman, J. T., Fine, L. G., Brown, L. R., and Godovac-Zimmermann, J. (2005). Proteomics profiling of nuclear proteins for kidney fibroblasts suggests hypoxia, meiosis, and cancer may meet in the nucleus. Proteomics 5, 2819–2838.
Proteomics profiling of nuclear proteins for kidney fibroblasts suggests hypoxia, meiosis, and cancer may meet in the nucleus.CrossRef | 1:CAS:528:DC%2BD2MXnvVWhtLk%3D&md5=e5be2f9d48e4e4aa7a0b9d671b582001CAS | open url image1

Sinner, D., Caviglia, J. M., Jawerbaum, A., Igal, R. A., and Gonzalez, E. (2003). Lipid metabolism in the embryos of diabetic rats during early organogenesis: modulatory effect of prostaglandin E2. Reprod. Fertil. Dev. 15, 75–80.
Lipid metabolism in the embryos of diabetic rats during early organogenesis: modulatory effect of prostaglandin E2.CrossRef | 1:CAS:528:DC%2BD3sXmtFSqsbY%3D&md5=83909f478a724ae15fbf55ce5286f4b7CAS | open url image1

Suzuki, R., Lee, K., Jing, E., Biddinger, S. B., McDonald, J. G., Montine, T. J., Craft, S., and Kahn, C. R. (2010). Diabetes and insulin in regulation of brain cholesterol metabolism. Cell Metab. 12, 567–579.
Diabetes and insulin in regulation of brain cholesterol metabolism.CrossRef | 1:CAS:528:DC%2BC3cXhsVyhs7vL&md5=16d490d0301d0544f46f9589a51a2fb0CAS | open url image1

Swami, S., Sztalryd, C., and Kraemer, F. B. (1996). Effects of streptozotocin-induced diabetes on low density lipoprotein receptor expression in rat adipose tissue. J. Lipid Res. 37, 229–236.
| 1:CAS:528:DyaK28XhsFClsr4%3D&md5=d2f9c9247009286323f41bd3b2dd1c91CAS | open url image1

Takahashi, S., Kawarabayasi, Y., Nakai, T., Sakai, J., and Yamamoto, T. (1992). Rabbit very low density lipoprotein receptor: a low density lipoprotein receptor-like protein with distinct ligand specificity. Proc. Natl. Acad. Sci. USA 89, 9252–9256.
Rabbit very low density lipoprotein receptor: a low density lipoprotein receptor-like protein with distinct ligand specificity.CrossRef | 1:CAS:528:DyaK3sXkvFWru74%3D&md5=73b4ad48c43b514d6d6dd914a037717dCAS | open url image1

Tarrade, A., Rousseau-Ralliard, D., Aubrière, M.-C., Peynot, N., Dahirel, M., Bertrand-Michel, J., Aguirre-Lavin, T., Morel, O., Beaujean, N., Duranthon, V., and Chavatte-Palmer, P. (2013). Sexual dimorphism of the feto-placental phenotype in response to a high fat and control maternal diets in a rabbit model. PLoS One 8, e83458.
Sexual dimorphism of the feto-placental phenotype in response to a high fat and control maternal diets in a rabbit model.CrossRef | open url image1

Thieme, R., Schindler, M., Ramin, N., Fischer, S., Mühleck, B., Fischer, B., and Navarrete Santos, A. (2012). Insulin growth factor adjustment in preimplantation rabbit blastocysts and uterine tissues in response to maternal type 1 diabetes. Mol. Cell. Endocrinol. 358, 96–103.
Insulin growth factor adjustment in preimplantation rabbit blastocysts and uterine tissues in response to maternal type 1 diabetes.CrossRef | 1:CAS:528:DC%2BC38Xlt1yltLw%3D&md5=8507bb5c57a3a6a1c8bd0f8cbf3f1f50CAS | open url image1

Tint, G. S., Irons, M., Elias, E. R., Batta, A. K., Frieden, R., Chen, T. S., and Salen, G. (1994). Defective cholesterol biosynthesis associated with the Smith–Lemli–Opitz syndrome. N. Engl. J. Med. 330, 107–113.
Defective cholesterol biosynthesis associated with the Smith–Lemli–Opitz syndrome.CrossRef | 1:STN:280:DyaK2c%2FotF2jsw%3D%3D&md5=8926f09d359762154a2d472d05ecdf44CAS | open url image1

Tint, G. S., Yu, H., Shang, Q., Xu, G., and Patel, S. B. (2006). The use of the Dhcr7 knockout mouse to accurately determine the origin of fetal sterols. J. Lipid Res. 47, 1535–1541.
The use of the Dhcr7 knockout mouse to accurately determine the origin of fetal sterols.CrossRef | 1:CAS:528:DC%2BD28XntVChurs%3D&md5=a76942b54f790cdded0777c1bc6b3159CAS | open url image1

Vercheval, M., De Hertogh, R., Pampfer, S., Vanderheyden, I., Michiels, B., De Bernardi, P., and De Meyer, R. (1990). Experimental diabetes impairs rat embryo development during the preimplantation period. Diabetologia 33, 187–191.
Experimental diabetes impairs rat embryo development during the preimplantation period.CrossRef | 1:STN:280:DyaK3c3mvFGjsg%3D%3D&md5=8b1efe8a3d569b022e771e73b7c89a5bCAS | open url image1

Wagner, M., and Siddiqui, M. Q. (2007). Signal transduction in early heart development (I): cardiogenic induction and heart tube formation. Exp. Biol. Med. (Maywood) 232, 852–865.
| 1:CAS:528:DC%2BD2sXnsFWjtLs%3D&md5=272004335419943ab3640c0cedbd9407CAS | open url image1

Watkins, A. J., and Fleming, T. P. (2009). Blastocyst environment and its influence on offspring cardiovascular health: the heart of the matter. J. Anat. 215, 52–59.
Blastocyst environment and its influence on offspring cardiovascular health: the heart of the matter.CrossRef | open url image1

Watkins, A. J., Papenbrock, T., and Fleming, T. P. (2008). The preimplantation embryo: handle with care. Semin. Reprod. Med. 26, 175–185.
The preimplantation embryo: handle with care.CrossRef | 1:CAS:528:DC%2BD1cXkt1Wgsrk%3D&md5=11bb4768e857d06a402325f6cc19dc6fCAS | open url image1

Woollett, L. A. (1996). Origin of cholesterol in the fetal golden Syrian hamster: contribution of de novo sterol synthesis and maternal-derived lipoprotein cholesterol. J. Lipid Res. 37, 1246–1257.
| 1:CAS:528:DyaK28XktFalsb8%3D&md5=c0911744d251b754a2c901b5306a717aCAS | open url image1

Woollett, L. A. (2005). Maternal cholesterol in fetal development: transport of cholesterol from the maternal to the fetal circulation. Am. J. Clin. Nutr. 82, 1155–1161.
| 1:CAS:528:DC%2BD2MXhtlehurbN&md5=e482a9052d045f5974b7d2c7a1207022CAS | open url image1

Xie, X., Liao, H., Dang, H., Pang, W., Guan, Y., Wang, X., Shyy, J. Y.-J., Zhu, Y., and Sladek, F. M. (2009). Down-regulation of hepatic HNF4alpha gene expression during hyperinsulinemia via SREBPs. Mol. Endocrinol. 23, 434–443.
Down-regulation of hepatic HNF4alpha gene expression during hyperinsulinemia via SREBPs.CrossRef | 1:CAS:528:DC%2BD1MXktlSiu7k%3D&md5=c4588dc4f81c3ca12ffbcb8bf0b64732CAS | open url image1

Yang, T., Espenshade, P. J., Wright, M. E., Yabe, D., Gong, Y., Aebersold, R., Goldstein, J. L., and Brown, M. S. (2002). Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell 110, 489–500.
Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER.CrossRef | 1:CAS:528:DC%2BD38Xmslyjt70%3D&md5=43f1b1f088cd8d68562d5b196d2ac2daCAS | open url image1

Yao, L., Jenkins, K., Horn, P. S., Lichtenberg, M. H., and Woollett, L. A. (2007). Inability to fully suppress sterol synthesis rates with exogenous sterol in embryonic and extraembyronic fetal tissues. Biochim. Biophys. Acta 1771, 1372–1379.
Inability to fully suppress sterol synthesis rates with exogenous sterol in embryonic and extraembyronic fetal tissues.CrossRef | 1:CAS:528:DC%2BD2sXhsVeqtb7O&md5=b727b9cad0a532f7d274c6fa2ce89444CAS | open url image1

Yoshida, S., and Wada, Y. (2005). Transfer of maternal cholesterol to embryo and fetus in pregnant mice. J. Lipid Res. 46, 2168–2174.
Transfer of maternal cholesterol to embryo and fetus in pregnant mice.CrossRef | 1:CAS:528:DC%2BD2MXhtVygsrzJ&md5=7763434008f51d0fd37fba3830c71387CAS | open url image1



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