Animal Reproduction (AR)
https://animal-reproduction.org/article/doi/10.1590/1984-3143-AR2021-0134
Animal Reproduction (AR)
THEMATIC SECTION: VIII INTERNATIONAL SYMPOSIUM ON ANIMAL BIOLOGY OF REPRODUCTION (ISABR 2020/2021)

Rodent models in placental research. Implications for fetal origins of adult disease

Nicole Aguilera; Francisca Salas-Pérez; Macarena Ortíz; Daniela Álvarez; Bárbara Echiburú; Manuel Maliqueo

Downloads: 0
Views: 116

Abstract

Abstract: Rodent models in rats, mice, and guinea pigs have been extremely helpful to gain insight into pregnancy physiology and pathologies-related. Moreover, they have allowed understanding the mechanism that links an adverse intrauterine environment with the origin of adult disease. In this regard, the effects of diverse maternal conditions, such as undernutrition, obesity, hypoxia, and hyperandrogenism on placental function and its long-term consequences for the offspring, have been widely analyzed through rodents models involving dietary manipulations, modifications in environmental oxygen, surgical and pharmacological procedures that reduce uteroplacental blood flow and administrations of exogenous testosterone and dihydrotestosterone (DHT) mimicking maternal androgen excess. Both in human and in rodent models, these interventions induce modifications of placental morphology, transport of glucose, amino acid, and fatty acids, steroid synthesis, and signaling pathways control placental function. These changes are associated with the increase of pro-inflammatory and oxidative stress markers. For its part, offspring exhibit alterations in organs involved in metabolic control such as the hypothalamus, adipose tissue, liver, skeletal muscle, and pancreas altering the intake and preferences for certain foods, the metabolism of glucose and lipid, and hormonal function leading to fat accumulation, insulin resistance, fatty liver, dyslipidemia, and elevated glucose levels. Therefore, the present review discusses the evidence emerging from rodent models that relate maternal nutrition, hypoxia, and androgen exposure to the maternal mechanisms that lead to fetal programming and their metabolic consequences in postnatal life.

Keywords

rodent models, maternal nutrition, hypoxia, and hyperandrogenism

References

Aiken CE, Tarry-Adkins JL, Spiroski A-M, Nuzzo AM, Ashmore TJ, Rolfo A, Sutherland MJ, Camm EJ, Giussani DA, Ozanne SE. Chronic gestational hypoxia accelerates ovarian aging and lowers ovarian reserve in next-generation adult rats. FASEB J. 2019;33(6):7758-66. http://dx.doi.org/10.1096/fj.201802772R. PMid:30888848.

Alves MB, Dalle Molle R, Desai M, Ross MG, Silveira PP. Increased palatable food intake and response to food cues in intrauterine growth-restricted rats are related to tyrosine hydroxylase content in the orbitofrontal cortex and nucleus accumbens. Behav Brain Res. 2015;287:73-81. http://dx.doi.org/10.1016/j.bbr.2015.03.019. PMid:25796489.

Andersen MD, Alstrup AKO, Duvald CS, Mikkelsen EFR, Vendelbo MH, Ovesen PG, Pedersen M. Animal models of fetal medicine and obstetrics. In: Ibeh B, editor. Experimental animal models of human diseases: an effective therapeutic strategy. London: InTech; 2018. http://dx.doi.org/10.5772/intechopen.74038.

Ashino NG, Saito KN, Souza FD, Nakutz FS, Roman EA, Velloso LA, Torsoni AS, Torsoni MA. Maternal high-fat feeding through pregnancy and lactation predisposes mouse offspring to molecular insulin resistance and fatty liver. J Nutr Biochem. 2012;23(4):341-8. http://dx.doi.org/10.1016/j.jnutbio.2010.12.011. PMid:21543214.

Barrand S, Crowley TM, Wood-Bradley RJ, De Jong KA, Armitage JA. Impact of maternal high fat diet on hypothalamic transcriptome in neonatal Sprague Dawley rats. PLoS One. 2017;12(12):e0189492. http://dx.doi.org/10.1371/journal.pone.0189492. PMid:29240779.

Barrett ES, Mbowe O, Thurston SW, Butts S, Wang C, Nguyen R, Bush N, Redmon JB, Sheshu S, Swan SH, Sathyanarayana S. Predictors of steroid hormone concentrations in early pregnancy: results from a multi-center cohort. Matern Child Health J. 2019;23(3):397-407. http://dx.doi.org/10.1007/s10995-018-02705-0. PMid:30659461.

Barros Mucci D, Kusinski LC, Wilsmore P, Loche E, Pantaleão LC, Ashmore TJ, Blackmore HL, Fernandez-Twinn DS, Carmo MDGTD, Ozanne SE. Impact of maternal obesity on placental transcriptome and morphology associated with fetal growth restriction in mice. Int J Obes. 2020;44(5):1087-96. http://dx.doi.org/10.1038/s41366-020-0561-3. PMid:32203108.

Baserga M, Hale MA, Wang ZM, Yu X, Callaway CW, McKnight RA, Lane RH. Uteroplacental insufficiency alters nephrogenesis and downregulates cyclooxygenase-2 expression in a model of IUGR with adult-onset hypertension. Am J Physiol Regul Integr Comp Physiol. 2007;292(5):R1943-55. http://dx.doi.org/10.1152/ajpregu.00558.2006. PMid:17272666.

Bayol SA, Farrington SJ, Stickland NC. A maternal ‘junk food’ diet in pregnancy and lactation promotes an exacerbated taste for ‘junk food’ and a greater propensity for obesity in rat offspring. Br J Nutr. 2007;98(4):843-51.. http://dx.doi.org/10.1017/S0007114507812037. PMid:17697422.

Bayol SA, Simbi BH, Bertrand JA, Stickland NC. Offspring from mothers fed a ‘junk food’ diet in pregnancy and lactation exhibit exacerbated adiposity that is more pronounced in females. J Physiol. 2008;586(13):3219-30. http://dx.doi.org/10.1113/jphysiol.2008.153817. PMid:18467362.

Bellinger L, Lilley C, Langley-Evans SC. Prenatal exposure to a maternal low-protein diet programmes a preference for high-fat foods in the young adult rat. Br J Nutr. 2004;92(3):513-20. http://dx.doi.org/10.1079/BJN20041224. PMid:15469656.

Boyle JA, Teede HJ. PCOS: refining diagnostic features in PCOS to optimize health outcomes. Nat Rev Endocrinol. 2016;12(11):630-1. http://dx.doi.org/10.1038/nrendo.2016.157. PMid:27636732.

Caanen MR, Kuijper EA, Hompes PG, Kushnir MM, Rockwood AL, Meikle WA, Homburg R, Lambalk CB. Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome. Eur J Endocrinol. 2016;174(1):25-32. http://dx.doi.org/10.1530/EJE-15-0699. PMid:26586837.

Caldwell AS, Middleton LJ, Jimenez M, Desai R, McMahon AC, Allan CM, Handelsman DJ, Walters KA. Characterization of reproductive, metabolic, and endocrine features of polycystic ovary syndrome in female hyperandrogenic mouse models. Endocrinology. 2014;155(8):3146-59. http://dx.doi.org/10.1210/en.2014-1196. PMid:24877633.

Camm EJ, Martin-Gronert MS, Wright NL, Hansell JA, Ozanne SE, Giussani DA. Prenatal hypoxia independent of undernutrition promotes molecular markers of insulin resistance in adult offspring. FASEB J. 2011;25(1):420-7. http://dx.doi.org/10.1096/fj.10-158188. PMid:20923964.

Cao B, Liu C, Zhang Q, Dong Y. Maternal high-fat diet leads to non-alcoholic fatty liver disease through upregulating hepatic SCD1 expression in neonate rats. Front Nutr. 2020;7:581723. http://dx.doi.org/10.3389/fnut.2020.581723. PMid:33282902.

Cao L, Mao C, Li S, Zhang Y, Lv J, Jiang S, Xu Z. Hepatic insulin signaling changes: possible mechanism in prenatal hypoxia-increased susceptibility of fatty liver in adulthood. Endocrinology. 2012;153(10):4955-65. http://dx.doi.org/10.1210/en.2012-1349. PMid:22903613.

Capellini I, Venditti C, Barton RA. Placentation and maternal investment in mammals. Am Nat. 2011;177(1):86-98. http://dx.doi.org/10.1086/657435. PMid:21087154.

Carlsen SM, Jacobsen G, Romundstad P. Maternal testosterone levels during pregnancy are associated with offspring size at birth. Eur J Endocrinol. 2006;155(2):365-70. http://dx.doi.org/10.1530/eje.1.02200. PMid:16868152.

Chen H, Simar D, Lambert K, Mercier J, Morris MJ. Maternal and postnatal overnutrition differentially impact appetite regulators and fuel metabolism. Endocrinology. 2008;149(11):5348-56. http://dx.doi.org/10.1210/en.2008-0582. PMid:18635655.

Chu A, Casero D, Thamotharan S, Wadehra M, Cosi A, Devaskar SU. The placental transcriptome in late gestational hypoxia resulting in murine intrauterine growth restriction parallels increased risk of adult cardiometabolic disease. Sci Rep. 2019;9(1):1243. http://dx.doi.org/10.1038/s41598-018-37627-y. PMid:30718791.

Coan PM, Vaughan OR, Sekita Y, Finn SL, Burton GJ, Constancia M, Fowden AL. Adaptations in placental phenotype support fetal growth during undernutrition of pregnant mice. J Physiol. 2010;588(3):527-38. http://dx.doi.org/10.1113/jphysiol.2009.181214. PMid:19948659.

Connor KL, Kibschull M, Matysiak-Zablocki E, Nguyen TT-TN, Matthews SG, Lye SJ, Bloise E. Maternal malnutrition impacts placental morphology and transporter expression: an origin for poor offspring growth. J Nutr Biochem. 2020;78:108329. http://dx.doi.org/10.1016/j.jnutbio.2019.108329. PMid:32004932.

Csapo AI, Puri CP, Tarró S. Relationship between timing of ovariectomy and maintenance of pregnancy in the guinea-pig. Prostaglandins. 1981;22(1):131-40. http://dx.doi.org/10.1016/0090-6980(81)90060-5. PMid:7291595.

Cuffe JSM, Walton SL, Singh RR, Spiers JG, Bielefeldt-Ohmann H, Wilkinson L, Little MH, Moritz KM. Mid- to late term hypoxia in the mouse alters placental morphology, glucocorticoid regulatory pathways and nutrient transporters in a sex-specific manner. J Physiol. 2014;592(14):3127-41. http://dx.doi.org/10.1113/jphysiol.2014.272856. PMid:24801305.

Davisson RL, Hoffmann DS, Butz GM, Aldape G, Schlager G, Merrill DC, Sethi S, Weiss RM, Bates JN. Discovery of a spontaneous genetic mouse model of preeclampsia. Hypertension. 2002;39(2):337-42. http://dx.doi.org/10.1161/hy02t2.102904. PMid:11882569.

Dean A, Smith LB, Macpherson S, Sharpe RM. The effect of dihydrotestosterone exposure during or prior to the masculinization programming window on reproductive development in male and female rats. Int J Androl. 2012;35(3):330-9. http://dx.doi.org/10.1111/j.1365-2605.2011.01236.x. PMid:22248293.

Elahi MM, Cagampang FR, Mukhtar D, Anthony FW, Ohri SK, Hanson MA. Long-term maternal high-fat feeding from weaning through pregnancy and lactation predisposes offspring to hypertension, raised plasma lipids and fatty liver in mice. Br J Nutr. 2009;102(4):514-9. http://dx.doi.org/10.1017/S000711450820749X. PMid:19203419.

Erlandsson L, Nääv Å, Hennessy A, Vaiman D, Gram M, Åkerström B, Hansson SR. Inventory of novel animal models addressing etiology of preeclampsia in the development of new therapeutic/intervention opportunities. Am J Reprod Immunol. 2016;75(3):402-10. http://dx.doi.org/10.1111/aji.12460. PMid:26685057.

Fajersztajn L, Veras MM. Hypoxia: from placental development to fetal programming. Birth Defects Res. 2017;109(17):1377-85. http://dx.doi.org/10.1002/bdr2.1142. PMid:29105382.

Fernandez-Twinn DS, Wayman A, Ekizoglou S, Martin MS, Hales CN, Ozanne SE. Maternal protein restriction leads to hyperinsulinemia and reduced insulin-signaling protein expression in 21-mo-old female rat offspring. Am J Physiol Regul Integr Comp Physiol. 2005;288(2):R368-73. http://dx.doi.org/10.1152/ajpregu.00206.2004. PMid:15514105.

Fornes R, Maliqueo M, Hu M, Hadi L, Jimenez-Andrade JM, Ebefors K, Nyström J, Labrie F, Jansson T, Benrick A, Stener-Victorin E. The effect of androgen excess on maternal metabolism, placental function and fetal growth in obese dams. Sci Rep. 2017;7(1):8066. http://dx.doi.org/10.1038/s41598-017-08559-w. PMid:28808352.

Fukami T, Sun X, Li T, Desai M, Ross M. Mechanism of programmed obesity in intrauterine fetal growth restricted offspring: paradoxically enhanced appetite stimulation in fed and fasting states. Reprod Sci. 2012;19(4):423-30. http://dx.doi.org/10.1177/1933719111424448. PMid:22344733.

Furukawa S, Kuroda Y, Sugiyama A. A comparison of the histological structure of the placenta in experimental animals. J Toxicol Pathol. 2014;27(1):11-8. http://dx.doi.org/10.1293/tox.2013-0060. PMid:24791062.

Gao H, Yallampalli U, Yallampalli C. Gestational protein restriction reduces expression of Hsd17b2 in rat placental labyrinth. Biol Reprod. 2012;87(3):68. http://dx.doi.org/10.1095/biolreprod.112.100479. PMid:22837477.

Ghosh P, Bitsanis D, Ghebremeskel K, Crawford MA, Poston L. Abnormal aortic fatty acid composition and small artery function in offspring of rats fed a high fat diet in pregnancy. J Physiol. 2001;533(Pt 3):815-22. http://dx.doi.org/10.1111/j.1469-7793.2001.00815.x. PMid:11410637.

Giussani DA, Camm EJ, Niu Y, Richter HG, Blanco CE, Gottschalk R, Blake EZ, Horder KA, Thakor AS, Hansell JA, Kane AD, Wooding FBP, Cross CM, Herrera EA. Developmental programming of cardiovascular dysfunction by prenatal hypoxia and oxidative stress. PLoS One. 2012;7(2):e31017. http://dx.doi.org/10.1371/journal.pone.0031017. PMid:22348036.

Gonzalez PN, Gasperowicz M, Barbeito-Andrés J, Klenin N, Cross JC, Hallgrímsson B. Chronic protein restriction in mice impacts placental function and maternal body weight before fetal growth. PLoS One. 2016;11(3):e0152227. http://dx.doi.org/10.1371/journal.pone.0152227. PMid:27018791.

Hales CN, Barker DJP. The thrifty phenotype hypothesis. Br Med Bull. 2001;60(1):5-20. http://dx.doi.org/10.1093/bmb/60.1.5. PMid:11809615.

Higgins JS, Vaughan OR, Fernandez de Liger E, Fowden AL, Sferruzzi-Perri AN. Placental phenotype and resource allocation to fetal growth are modified by the timing and degree of hypoxia during mouse pregnancy. J Physiol. 2016;594(5):1341-56. http://dx.doi.org/10.1113/JP271057. PMid:26377136.

Hu M, Richard JE, Maliqueo M, Kokosar M, Fornes R, Benrick A, Jansson T, Ohlsson C, Wu X, Skibicka KP, Stener-Victorin E. Maternal testosterone exposure increases anxiety-like behavior and impacts the limbic system in the offspring. Proc Natl Acad Sci USA. 2015;112(46):14348-53. http://dx.doi.org/10.1073/pnas.1507514112. PMid:26578781.

Huang S-TJ, Vo KCT, Lyell DJ, Faessen GH, Tulac S, Tibshirani R, Giaccia AJ, Giudice LC. Developmental response to hypoxia. FASEB J. 2004;18(12):1348-65. http://dx.doi.org/10.1096/fj.03-1377com. PMid:15333578.

Ivy CM, Scott GR. Life-long exposure to hypoxia affects metabolism and respiratory physiology across life stages in high-altitude deer mice (Peromyscus maniculatus). J Exp Biol. 2021;224(1). http://dx.doi.org/10.1242/jeb.237024. PMid:33268530.

Jakoubek V, Bíbová J, Herget J, Hampl V. Chronic hypoxia increases fetoplacental vascular resistance and vasoconstrictor reactivity in the rat. Am J Physiol Heart Circ Physiol. 2008;294(4):H1638-44. http://dx.doi.org/10.1152/ajpheart.01120.2007. PMid:18310520.

Jansson N, Pettersson J, Haafiz A, Ericsson A, Palmberg I, Tranberg M, Ganapathy V, Powell TL, Jansson T. Down-regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet. J Physiol. 2006;576(Pt 3):935-46. http://dx.doi.org/10.1113/jphysiol.2006.116509. PMid:16916910.

Kauffman AS, Thackray VG, Ryan GE, Tolson KP, Glidewell-Kenney CA, Semaan SJ, Poling MC, Iwata N, Breen KM, Duleba AJ, Stener-Victorin E, Shimasaki S, Webster NJ, Mellon PL. A novel letrozole model recapitulates both the reproductive and metabolic phenotypes of polycystic ovary syndrome in female mice. Biol Reprod. 2015;93(3):69. http://dx.doi.org/10.1095/biolreprod.115.131631. PMid:26203175.

Khalil RA, Granger JP. Vascular mechanisms of increased arterial pressure in preeclampsia: lessons from animal models. Am J Physiol Regul Integr Comp Physiol. 2002;283(1):R29-45. http://dx.doi.org/10.1152/ajpregu.00762.2001. PMid:12069928.

Khalyfa A, Cortese R, Qiao Z, Ye H, Bao R, Andrade J, Gozal D. Late gestational intermittent hypoxia induces metabolic and epigenetic changes in male adult offspring mice. J Physiol. 2017;595(8):2551-68. http://dx.doi.org/10.1113/JP273570. PMid:28090638.

Khan IY, Dekou V, Douglas G, Jensen R, Hanson MA, Poston L, Taylor PD. A high-fat diet during rat pregnancy or suckling induces cardiovascular dysfunction in adult offspring. Am J Physiol Regul Integr Comp Physiol. 2005;288(1):R127-33. http://dx.doi.org/10.1152/ajpregu.00354.2004. PMid:15308487.

Kim DW, Young SL, Grattan DR, Jasoni CL. Obesity during pregnancy disrupts placental morphology, cell proliferation, and inflammation in a sex-specific manner across gestation in the mouse. Biol Reprod. 2014;90(6):130. http://dx.doi.org/10.1095/biolreprod.113.117259. PMid:24829026.

Kingdom JCP, Kaufmann P. Oxygen and placental villous development: origins of fetal hypoxia. Placenta. 1997;18(8):613-21. http://dx.doi.org/10.1016/S0143-4004(97)90000-X. PMid:9364596.

Kumar S, Gordon GH, Abbott DH, Mishra JS. Androgens in maternal vascular and placental function: implications for preeclampsia pathogenesis. Reproduction. 2018;156(5):R155-67. http://dx.doi.org/10.1530/REP-18-0278. PMid:30325182.

Lecoutre S, Breton C. Maternal nutritional manipulations program adipose tissue dysfunction in offspring. Front Physiol. 2015;6:158. http://dx.doi.org/10.3389/fphys.2015.00158. PMid:26029119.

Li J, LaMarca B, Reckelhoff JF. A model of preeclampsia in rats: the reduced uterine perfusion pressure (RUPP) model. Am J Physiol Heart Circ Physiol. 2012;303(1):H1-8. http://dx.doi.org/10.1152/ajpheart.00117.2012. PMid:22523250.

Li M, Reynolds CM, Sloboda DM, Gray C, Vickers MH. Effects of taurine supplementation on hepatic markers of inflammation and lipid metabolism in mothers and offspring in the setting of maternal obesity. PLoS One. 2013;8(10):e76961. http://dx.doi.org/10.1371/journal.pone.0076961. PMid:24146946.

Liang C, DeCourcy K, Prater MR. High-saturated-fat diet induces gestational diabetes and placental vasculopathy in C57BL/6 mice. Metabolism. 2010;59(7):943-50. http://dx.doi.org/10.1016/j.metabol.2009.10.015. PMid:20022072.

Louwagie EJ, Larsen TD, Wachal AL, Baack ML. Placental lipid processing in response to a maternal high-fat diet and diabetes in rats. Pediatr Res. 2018;83(3):712-22. http://dx.doi.org/10.1038/pr.2017.288. PMid:29166372.

Määttä J, Sissala N, Dimova EY, Serpi R, Moore LG, Koivunen P. Hypoxia causes reductions in birth weight by altering maternal glucose and lipid metabolism. Sci Rep. 2018;8(1):13583. http://dx.doi.org/10.1038/s41598-018-31908-2. PMid:30206264.

Maliqueo M, Cruz G, Espina C, Contreras I, García M, Echiburú B, Crisosto N. Obesity during pregnancy affects sex steroid concentrations depending on fetal gender. Int J Obes. 2017;41(11):1636-45. http://dx.doi.org/10.1038/ijo.2017.159. PMid:28676682.

Maliqueo M, Sundström Poromaa I, Vanky E, Fornes R, Benrick A, Åkerud H, Stridsklev S, Labrie F, Jansson T, Stener-Victorin E. Placental STAT3 signaling is activated in women with polycystic ovary syndrome. Hum Reprod. 2015;30(3):692-700. http://dx.doi.org/10.1093/humrep/deu351. PMid:25609240.

Marciniak A, Patro-Małysza J, Kimber-Trojnar Ż, Marciniak B, Oleszczuk J, Leszczyńska-Gorzelak B. Fetal programming of the metabolic syndrome. Taiwan J Obstet Gynecol. 2017;56(2):133-8. http://dx.doi.org/10.1016/j.tjog.2017.01.001. PMid:28420495.

Matheson H, Veerbeek JHW, Charnock-Jones DS, Burton GJ, Yung HW. Morphological and molecular changes in the murine placenta exposed to normobaric hypoxia throughout pregnancy. J Physiol. 2016;594(5):1371-88. http://dx.doi.org/10.1113/JP271073. PMid:26278110.

McMillen IC, Edwards LJ, Duffield J, Muhlhausler BS. Regulation of leptin synthesis and secretion before birth: implications for the early programming of adult obesity. Reproduction. 2006;131(3):415-27. http://dx.doi.org/10.1530/rep.1.00303. PMid:16514185.

Molnär M, Söto T, Tóth T, Hertelendy F. Prolonged blockade of nitric oxide synthesis in gravid rats produces sustained hypertension, proteinuria, thrombocytopenia, and intrauterine growth retardation. Am J Obstet Gynecol. 1994;170(5):1458-66. http://dx.doi.org/10.1016/S0002-9378(13)90488-9. PMid:7909994.

Morris MJ, Chen H. Established maternal obesity in the rat reprograms hypothalamic appetite regulators and leptin signaling at birth. Int J Obes. 2009;33(1):115-22. http://dx.doi.org/10.1038/ijo.2008.213. PMid:18982008.

Morrison JL, Botting KJ, Darby JRT, David AL, Dyson RM, Gatford KL, Gray C, Herrera EA, Hirst JJ, Kim B, Kind KL, Krause BJ, Matthews SG, Palliser HK, Regnault TRH, Richardson BS, Sasaki A, Thompson LP, Berry MJ. Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic. J Physiol. 2018;596(23):5535-69. http://dx.doi.org/10.1113/JP274948. PMid:29633280.

Natale BV, Mehta P, Vu P, Schweitzer C, Gustin K, Kotadia R, Natale DRC. Reduced Uteroplacental Perfusion Pressure (RUPP) causes altered trophoblast differentiation and pericyte reduction in the mouse placenta labyrinth. Sci Rep. 2018;8(1):17162. http://dx.doi.org/10.1038/s41598-018-35606-x. PMid:30464252.

Neri C, Edlow AG. Effects of maternal obesity on fetal programming: molecular approaches. Cold Spring Harb Perspect Med. 2015;6(2):a026591. http://dx.doi.org/10.1101/cshperspect.a026591. PMid:26337113.

Niu Y, Kane AD, Lusby CM, Allison BJ, Chua YY, Kaandorp JJ, Nevin-Dolan R, Ashmore TJ, Blackmore HL, Derks JB, Ozanne SE, Giussani DA. Maternal allopurinol prevents cardiac dysfunction in adult male offspring programmed by chronic hypoxia during pregnancy. Hypertension. 2018;72(4):971-8. http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.11363. PMid:30354714.

Olive EL, Xiao E, Natale DR, Fisher SA. Oxygen and lack of oxygen in fetal and placental development, feto–placental coupling, and congenital heart defects. Birth Defects Res. 2018;110(20):1517-30. http://dx.doi.org/10.1002/bdr2.1430. PMid:30576091.

Ozanne SE, Lewis R, Jennings BJ, Hales CN. Early programming of weight gain in mice prevents the induction of obesity by a highly palatable diet. Clin Sci. 2004;106(2):141-5. http://dx.doi.org/10.1042/CS20030278. PMid:14507258.

Pampanini V, Jahnukainen K, Sahlin L, Germani D, Puglianiello A, Cianfarani S, Söder O. Impact of uteroplacental insufficiency on ovarian follicular pool in the rat. Reprod Biol Endocrinol. 2019;17(1):10. http://dx.doi.org/10.1186/s12958-019-0453-3. PMid:30630482.

Peeters LLH, Sheldon RE, Jones MD Jr, Makowski EL, Meschia G. Blood flow to fetal organs as a function of arterial oxygen content. Am J Obstet Gynecol. 1979;135(5):637-46. http://dx.doi.org/10.1016/S0002-9378(16)32989-1. PMid:507116.

Perrone S, Santacroce A, Picardi A, Buonocore G. Fetal programming and early identification of newborns at high risk of free radical-mediated diseases. World J Clin Pediatr. 2016;5(2):172-81. http://dx.doi.org/10.5409/wjcp.v5.i2.172. PMid:27170927.

Petry CJ, Dorling MW, Wang CL, Pawlak DB, Ozanne SE. Catecholamine levels and receptor expression in low protein rat offspring. Diabet Med. 2000;17(12):848-53. http://dx.doi.org/10.1046/j.1464-5491.2000.00392.x. PMid:11168327.

Phuthong S, Reyes-Hernández CG, Rodríguez-Rodríguez P, Ramiro-Cortijo D, Gil-Ortega M, González-Blázquez R, González MC, López de Pablo AL, Arribas SM. Sex differences in placental protein expression and efficiency in a rat model of fetal programming induced by maternal undernutrition. Int J Mol Sci. 2020;22(1):237. http://dx.doi.org/10.3390/ijms22010237. PMid:33379399.

Redman CWG. Preeclampsia: a multi-stress disorder. Rev Med Interne. 2011;32(Suppl. 1):S41-4. http://dx.doi.org/10.1016/j.revmed.2011.03.331. PMid:21530020.

Risal S, Manti M, Lu H, Fornes R, Larsson H, Benrick A, Deng Q, Cesta CE, Rosenqvist MA, Stener-Victorin E. Prenatal androgen exposure causes a sexually dimorphic transgenerational increase in offspring susceptibility to anxiety disorders. Transl Psychiatry. 2021;11(1):45. http://dx.doi.org/10.1038/s41398-020-01183-9. PMid:33441551.

Risal S, Pei Y, Lu H, Manti M, Fornes R, Pui HP, Zhao Z, Massart J, Ohlsson C, Lindgren E, Crisosto N, Maliqueo M, Echiburu B, Ladron de Guevara A, Sir-Petermann T, Larsson H, Rosenqvist MA, Cesta CE, Benrick A, Deng Q, Stener-Victorin E. Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome. Nat Med. 2019;25(12):1894-904. http://dx.doi.org/10.1038/s41591-019-0666-1. PMid:31792459.

Roberts JM, Hubel CA. The two stage model of preeclampsia: variations on the theme. Placenta. 2009;30(Suppl. A):32-7. http://dx.doi.org/10.1016/j.placenta.2008.11.009. PMid:19070896.

Rosario FJ, Jansson N, Kanai Y, Prasad PD, Powell TL, Jansson T. Maternal protein restriction in the rat inhibits placental insulin, mTOR, and STAT3 signaling and down-regulates placental amino acid transporters. Endocrinology. 2011;152(3):1119-29. http://dx.doi.org/10.1210/en.2010-1153. PMid:21285325.

Rosario FJ, Kanai Y, Powell TL, Jansson T. Increased placental nutrient transport in a novel mouse model of maternal obesity with fetal overgrowth. Obesity. 2015;23(8):1663-70. http://dx.doi.org/10.1002/oby.21165. PMid:26193061.

Rosario FJ, Powell TL, Jansson T. Activation of placental insulin and mTOR signaling in a mouse model of maternal obesity associated with fetal overgrowth. Am J Physiol Regul Integr Comp Physiol. 2016;310(1):R87-93. http://dx.doi.org/10.1152/ajpregu.00356.2015. PMid:26491103.

Samuelsson AM, Matthews PA, Argenton M, Christie MR, McConnell JM, Jansen EHJM, Piersma AH, Ozanne SE, Twinn DF, Remacle C, Rowlerson A, Poston L, Taylor PD. Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: a novel murine model of developmental programming. Hypertension. 2008;51(2):383-92. http://dx.doi.org/10.1161/HYPERTENSIONAHA.107.101477. PMid:18086952.

Santillan MK, Pelham CJ, Ketsawatsomkron P, Santillan DA, Davis DR, Devor EJ, Gibson-Corley KN, Scroggins SM, Grobe JL, Yang B, Hunter SK, Sigmund CD. Pregnant mice lacking indoleamine 2,3-dioxygenase exhibit preeclampsia phenotypes. Physiol Rep. 2015;3(1):e12257. http://dx.doi.org/10.14814/phy2.12257. PMid:25602015.

Santillan MK, Santillan DA, Scroggins SM, Min JY, Sandgren JA, Pearson NA, Leslie KK, Hunter SK, Zamba GKD, Gibson-Corley KN, Grobe JL. Vasopressin in preeclampsia: a novel very early human pregnancy biomarker and clinically relevant mouse model. Hypertension. 2014;64(4):852-9. http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.03848. PMid:25001273.

Sarli PM, Manousopoulou A, Efthymiou E, Zouridis A, Potiris A, Pervanidou P, Panoulis K, Vlahos N, Deligeoroglou E, Garbis SD, Eleftheriades M. Liver proteome profile of growth restricted and appropriately grown newborn Wistar rats associated with maternal undernutrition. Front Endocrinol. 2021;12:684220. http://dx.doi.org/10.3389/fendo.2021.684220. PMid:34127923.

Sathishkumar K, Elkins R, Chinnathambi V, Gao H, Hankins GDV, Yallampalli C. Prenatal testosterone-induced fetal growth restriction is associated with down-regulation of rat placental amino acid transport. Reprod Biol Endocrinol. 2011;9(1):110. http://dx.doi.org/10.1186/1477-7827-9-110. PMid:21812961.

Sferruzzi-Perri AN, Camm EJ. The programming power of the placenta. Front Physiol. 2016;7:33. http://dx.doi.org/10.3389/fphys.2016.00033. PMid:27014074.

Siragher E, Sferruzzi-Perri AN. Placental hypoxia: what have we learnt from small animal models? Placenta. 2021;113:29-47. http://dx.doi.org/10.1016/j.placenta.2021.03.018. PMid:34074553.

Skeffington KL, Higgins JS, Mahmoud AD, Evans AM, Sferruzzi-Perri AN, Fowden AL, Yung HW, Burton GJ, Giussani DA, Moore LG. Hypoxia, AMPK activation and uterine artery vasoreactivity. J Physiol. 2016;594(5):1357-69. http://dx.doi.org/10.1113/JP270995. PMid:26110512.

Strakovsky RS, Zhang X, Zhou D, Pan YX. Gestational high fat diet programs hepatic phosphoenolpyruvate carboxykinase gene expression and histone modification in neonatal offspring rats. J Physiol. 2011;589(Pt 11):2707-17. http://dx.doi.org/10.1113/jphysiol.2010.203950. PMid:21486814.

Strauss JF 3rd, Martinez F, Kiriakidou M. Placental steroid hormone synthesis: unique features and unanswered questions. Biol Reprod. 1996;54(2):303-11. http://dx.doi.org/10.1095/biolreprod54.2.303. PMid:8788180.

Sun M, Maliqueo M, Benrick A, Johansson J, Shao R, Hou L, Jansson T, Wu X, Stener-Victorin E. Maternal androgen excess reduces placental and fetal weights, increases placental steroidogenesis, and leads to long-term health effects in their female offspring. Am J Physiol Endocrinol Metab. 2012;303(11):E1373-85. http://dx.doi.org/10.1152/ajpendo.00421.2012. PMid:23047983.

Taylor PD, Samuelsson AM, Poston L. Maternal obesity and the developmental programming of hypertension: a role for leptin. Acta Physiol (Oxf). 2014;210(3):508-23. http://dx.doi.org/10.1111/apha.12223. PMid:24433239.

Thaete LG, Dewey ER, Neerhof MG. Endothelin and the regulation of uterine and placental perfusion in hypoxia-induced fetal growth restriction. J Soc Gynecol Investig. 2004;11(1):16-21. http://dx.doi.org/10.1016/j.jsgi.2003.07.001. PMid:14706678.

Thompson LP, Pence L, Pinkas G, Song H, Telugu BP. Placental hypoxia during early pregnancy causes maternal hypertension and placental insufficiency in the hypoxic guinea pig model. Biol Reprod. 2016;95(6):128. http://dx.doi.org/10.1095/biolreprod.116.142273. PMid:27806942.

Troisi R, Potischman N, Roberts J, Ness R, Crombleholme W, Lykins D, Siiteri P, Hoover RN. Maternal serum oestrogen and androgen concentrations in preeclamptic and uncomplicated pregnancies. Int J Epidemiol. 2003;32(3):455-60. http://dx.doi.org/10.1093/ije/dyg094. PMid:12777436.

Turan S, Aberdeen GW, Thompson LP. Chronic hypoxia alters maternal uterine and fetal hemodynamics in the full-term pregnant Guinea pig. Am J Physiol Regul Integr Comp Physiol. 2017;313(4):R330-9. http://dx.doi.org/10.1152/ajpregu.00056.2017. PMid:28679680.

Vargas VE, Gurung S, Grant B, Hyatt K, Singleton K, Myers SM, Saunders D, Njoku C, Towner R, Myers DA. Gestational hypoxia disrupts the neonatal leptin surge and programs hyperphagia and obesity in male offspring in the Sprague-Dawley rat. PLoS One. 2017;12(9):e0185272. http://dx.doi.org/10.1371/journal.pone.0185272. PMid:28957383.

Vickers MH, Breier BH, Cutfield WS, Hofman PL, Gluckman PD. Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition. Am J Physiol Endocrinol Metab. 2000;279(1):E83-7. http://dx.doi.org/10.1152/ajpendo.2000.279.1.E83. PMid:10893326.

Villarroel C, Salinas A, López P, Kohen P, Rencoret G, Devoto L, Codner E. Pregestational type 2 diabetes and gestational diabetes exhibit different sexual steroid profiles during pregnancy. Gynecol Endocrinol. 2017;33(3):212-7. http://dx.doi.org/10.1080/09513590.2016.1248933. PMid:27898283.

Vomhof-DeKrey E, Darland D, Ghribi O, Bundy A, Roemmich J, Claycombe K. Maternal low protein diet leads to placental angiogenic compensation via dysregulated M1/M2 macrophages and TNFα expression in Sprague-Dawley rats. J Reprod Immunol. 2016;118:9-17. http://dx.doi.org/10.1016/j.jri.2016.08.009. PMid:27596280.

Vucetic Z, Totoki K, Schoch H, Whitaker KW, Hill-Smith T, Lucki I, Reyes TM. Early life protein restriction alters dopamine circuitry. Neuroscience. 2010;168(2):359-70. http://dx.doi.org/10.1016/j.neuroscience.2010.04.010. PMid:20394806.

Walters KA, Bertoldo MJ, Handelsman DJ. Evidence from animal models on the pathogenesis of PCOS. Best Pract Res Clin Endocrinol Metab. 2018;32(3):271-81. http://dx.doi.org/10.1016/j.beem.2018.03.008. PMid:29779581.

Walters KA. Androgens in polycystic ovary syndrome: lessons from experimental models. Curr Opin Endocrinol Diabetes Obes. 2016;23(3):257-63. http://dx.doi.org/10.1097/MED.0000000000000245. PMid:26866639.

Walters KA. Role of androgens in normal and pathological ovarian function. Reproduction. 2015;149(4):R193-218. http://dx.doi.org/10.1530/REP-14-0517. PMid:25516989.

Warner MJ, Ozanne SE. Mechanisms involved in the developmental programming of adulthood disease. Biochem J. 2010;427(3):333-47. http://dx.doi.org/10.1042/BJ20091861. PMid:20388123.

Warshaw ML, Johnson DC, Khan I, Eckstein B, Gibori G. Placental secretion of androgens in the rat. Endocrinology. 1986;119(6):2642-8. http://dx.doi.org/10.1210/endo-119-6-2642. PMid:3490962.

Williams L, Seki Y, Vuguin PM, Charron MJ. Animal models of in utero exposure to a high fat diet: a review. Biochim Biophys Acta Mol Basis Dis. 2014;1842(3):507-19. http://dx.doi.org/10.1016/j.bbadis.2013.07.006. PMid:23872578.

Zhu W, Zhu J, Liang L, Shen Z, Wang Y. Maternal undernutrition leads to elevated hepatic triglycerides in male rat offspring due to increased expression of lipoprotein lipase. Mol Med Rep. 2016;13(5):4487-93. http://dx.doi.org/10.3892/mmr.2016.5040. PMid:27035287.
 


Submitted date:
12/23/2021

Accepted date:
03/21/2022

625f1da1a953952cc62931d2 animreprod Articles
Links & Downloads

Anim Reprod

Share this page
Page Sections