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Sexually dimorphic effects of maternal asthma during pregnancy on placental glucocorticoid metabolism and fetal growth

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Abstract

Human pregnancy is associated with sexually dimorphic differences in mortality and morbidity of the fetus with the male fetus experiencing the poorest outcome following complications such as pre-eclampsia, pre-term delivery and infection. The physiological mechanisms that confer these differences have not been well characterised in the human. Work conducted on the effect of maternal asthma during pregnancy, combining data collected from the mother, placenta and fetus has found some significant sex-related mechanistic differences associated with fetal growth in both normal pregnancies and pregnancies complicated by asthma. Specifically, sexually dimorphic differences have been found in placental glucocorticoid metabolism in male and female fetuses of normal pregnancies. In response to the presence of maternal asthma, only the female fetus alters placental glucocorticoid metabolism resulting in decreased growth. The male fetus does not alter placental function or growth in response to maternal asthma. As a result of the alterations in glucocorticoid metabolism in the female, downstream changes occur in pathways regulated by glucocorticoids. These data suggest that the female fetus adjusts placental function and reduces growth to compensate for maternal disease. However, the male fetus continues to grow in response to maternal asthma with no changes in placental function. This response by the male fetus may partially contribute to the increased risk of morbidity and mortality in this sex.

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References

  • Alfaidy N, Xiong ZG, Myatt L, Lye SJ, MacDonald JF, Challis JR (2001) Prostaglandin F2alpha potentiates cortisol production by stimulating 11beta-hydroxysteroid dehydrogenase 1: a novel feedback loop that may contribute to human labor. J Clin Endocrinol Metab 86:5585–5592

    Article  PubMed  Google Scholar 

  • Banjanin S, Kapoor A, Matthews SG (2004) Prenatal glucocorticoid exposure alters hypothalamic–pituitary–adrenal function and blood pressure in mature male guinea pigs. J Physiol (Lond) 558:305–318

    Article  Google Scholar 

  • Bazzett LB, Yaron Y, O’Brien JE, Critchfield G, Kramer RL, Ayoub M, Johnson MP, Evans MI (1998) Fetal gender impact on multiple-marker screening results. Am J Med Genet 76:369–371

    Article  PubMed  Google Scholar 

  • Beecroft N, Cochrane GM, Milburn HJ (1998) Effect of sex of fetus on asthma during pregnancy: blind prospective study. BMJ 317:856–857

    PubMed  Google Scholar 

  • Benassayag C, Souski I, Mignot TM, Robert B, Hassid J, Duc-Goiran P, Mondon F, Rebourcet R, Dehennin L, Nunez EA, Ferre F (2001) Corticosteroid-binding globulin status at the fetomaternal interface during human term pregnancy. Biol Reprod 64:812–821

    Article  PubMed  Google Scholar 

  • Benediktsson R, Calder AA, Edwards CR, Seckl JR (1997) Placental 11 beta-hydroxysteroid dehydrogenase: a key regulator of fetal glucocorticoid exposure. Clin Endocrinol (Oxf) 46:161–166

    Article  Google Scholar 

  • Bornstein SR, Rutkowski H (2002) The adrenal hormone metabolism in the immune/inflammatory reaction. Endocr Res 28:719–728

    Article  PubMed  Google Scholar 

  • Bracken MB, Triche EW, Belanger K, Saftlas A, Beckett WS, Leaderer BP (2003) Asthma symptoms, severity, and drug therapy: a prospective study of effects on 2205 pregnancies. Obstet Gynecol 102:739–752

    Article  PubMed  Google Scholar 

  • Bremme K, Eneroth P (1983) Fetal sex dependent hormone levels in early pregnant women with elevated maternal serum alpha-fetoprotein. Int J Gynaecol Obstet 21:451–457

    Article  PubMed  Google Scholar 

  • Bremme K, Lagerstrom M, Andersson O, Johansson S, Eneroth P (1990) Influences of maternal smoking, fetal sex on maternal serum oestriol, prolactin, hCG, and hPI levels. Arch Gynecol Obstet 247:95–103

    PubMed  Google Scholar 

  • Breslin MB, Vedeckis WV (1998) The human glucocorticoid receptor promoter upstream sequences contain binding sites for the ubiquitous transcription factor, Yin Yang 1. J Steroid Biochem Mol Biol 67:369–381

    Article  PubMed  Google Scholar 

  • Clifton VL, Murphy VE (2004) Maternal asthma as a model for examining fetal sex-specific effects on maternal physiology and placental mechanisms that regulate human fetal growth. Placenta 25 (Suppl A):S45–S52

    Article  PubMed  Google Scholar 

  • Cohn L, Elias JA, Chupp GL (2004) Asthma: mechanisms of disease persistence and progression. Annu Rev Immunol 22:789–815

    Article  PubMed  Google Scholar 

  • Condon J, Gosden C, Gardener D, Nickson P, Hewison M, Howie AJ, Stewart PM (1998) Expression of type 2 11beta-hydroxysteroid dehydrogenase and corticosteroid hormone receptors in early human fetal life. J Clin Endocrinol Metab 83:4490–4497

    Article  PubMed  Google Scholar 

  • Cooper MS, Bujalska I, Rabbitt E, Walker EA, Bland R, Sheppard MC, Hewison M, Stewart PM (2001) Modulation of 11beta-hydroxysteroid dehydrogenase isozymes by proinflammatory cytokines in osteoblasts: an autocrine switch from glucocorticoid inactivation to activation. J Bone Miner Res 16:1037–1044

    PubMed  Google Scholar 

  • Dancis J, Jansen V, Levitz M, Rosner W (1978) Effect of protein binding on transfer and metabolism of cortisol in perfused human placenta. J Clin Endocrinol Metab 46:863–868

    PubMed  Google Scholar 

  • Dodds L, Armson BA, Alexander S (1999) Use of asthma drugs is less among women pregnant with boys rather than girls. BMJ 318:1011

    Google Scholar 

  • Dombrowski MP, Schatz M, Wise R, Momirova V, Landon M, Mabie W, Newman RB, McNellis D, Hauth JC, Lindheimer M, Caritis SN, Leveno KJ, Meis P, Miodovnik M, Wapner RJ, Paul RH, Varner MW, O’Sullivan MJ, Thurnau GR, Conway DL (2004) Asthma during pregnancy. Obstet Gynecol 103:5–12

    PubMed  Google Scholar 

  • Edwards LJ, McMillen IC (2002) Impact of maternal undernutrition during the periconceptional period, fetal number, and fetal sex on the development of the hypothalamo-pituitary adrenal axis in sheep during late gestation. Biol Reprod 66:1562–1569

    PubMed  Google Scholar 

  • Egerman RS, Walker RA, Mercer BM, Doss JL, Sibai BM, Andersen RA (1998) Comparison between oral and intramuscular dexamethasone in suppressing unconjugated estriol levels during the third trimester. Am J Obstet Gynecol 179:1234–1236

    Article  PubMed  Google Scholar 

  • Evagelatou M, Peterson SL, Cooke BA (1997) Leukocytes modulate 11beta-hydroxysteroid dehydrogenase (11beta-HSD) activity in human granulosa-lutein cell cultures. Mol Cell Endocrinol 133:81–88

    Article  PubMed  Google Scholar 

  • Ferreira MA (2004) Inflammation in allergic asthma: initiating events, immunological response and risk factors. Respirology 9:16–24

    PubMed  Google Scholar 

  • Ficicioglu C, Kutlu T (2003) The role of androgens in the aetiology and pathology of pre-eclampsia. J Obstet Gynaecol 23:134–137

    Article  PubMed  Google Scholar 

  • Fitzsimons R, Greenberger PA, Patterson R (1986) Outcome of pregnancy in women requiring corticosteroids for severe asthma. J Allergy Clin Immunol 78:349–353

    PubMed  Google Scholar 

  • Fowden AL, Szemere J, Hughes P, Gilmour RS, Forhead AJ (1996) The effects of cortisol on the growth rate of the sheep fetus during late gestation. J Endocrinol 151:97–105

    Article  PubMed  Google Scholar 

  • French NP, Hagan R, Evans SF, Godfrey M, Newnham JP (1999) Repeated antenatal corticosteroids: size at birth and subsequent development. Am J Obstet Gynecol 180:114–121

    PubMed  Google Scholar 

  • Furuhashi N, Fukaya T, Kono H, Tachibana Y, Shinkawa O, Takahashi T (1982) Correlation of birth weights with umbilical cord serum LH-hCG, FSH, beta-hCG, estradiol, cortisol and testosterone levels. Gynecol Obstet Invest 13:241–248

    PubMed  Google Scholar 

  • Gitau R, Fisk NM, Teixeira JM, Cameron A, Glover V (2001) Fetal hypothalamic–pituitary–adrenal stress responses to invasive procedures are independent of maternal responses. J Clin Endocrinol Metab 86:104–109

    Article  PubMed  Google Scholar 

  • Goland RS, Jozak S, Warren WB, Conwell IM, Stark RI, Tropper PJ (1993) Elevated levels of umbilical cord plasma corticotropin-releasing hormone in growth-retarded fetuses. J Clin Endocrinol Metab 77:1174–1179

    Article  PubMed  Google Scholar 

  • Gordon M, Niswander KR, Berendes H, Kantor AG (1970) Fetal morbidity following potentially anoxigenic obstetric conditions. VII. Bronchial asthma. Am J Obstet Gynecol 106:421–429

    PubMed  Google Scholar 

  • Gravett MG, Hitti J, Hess DL, Eschenbach DA (2000) Intrauterine infection, preterm delivery: evidence for activation of the fetal hypothalamic–pituitary–adrenal axis. Am J Obstet Gynecol 182:1404–1413

    Article  PubMed  Google Scholar 

  • Halasz I, Rittenhouse PA, Zorrilla EP, Redei E (1997) Sexually dimorphic effects of maternal adrenalectomy on hypothalamic corticotrophin-releasing factor, glucocorticoid receptor and anterior pituitary POMC mRNA levels in rat neonates. Brain Res Dev Brain Res 100:198–204

    PubMed  Google Scholar 

  • Haning RV Jr, Curet LB, Poole WK, Boehnlein LM, Kuzma DL, Meier SM (1989) Effects of fetal sex and dexamethasone on preterm maternal serum concentrations of human chorionic gonadotropin, progesterone, estrone, estradiol, and estriol. Am J Obstet Gynecol 161:1549–1553

    PubMed  Google Scholar 

  • Harbuz MS, Nicholson SA, Gillham B, Lightman SL (1990) Stress responsiveness of hypothalamic corticotrophin-releasing factor and pituitary pro-opiomelanocortin mRNAs following high-dose glucocorticoid treatment and withdrawal in the rat. J Endocrinol 127:407–415

    PubMed  Google Scholar 

  • Heilmann P, Buchheim E, Wacker J, Ziegler R (2001) Alteration of the activity of the 11beta-hydroxysteroid dehydrogenase in pregnancy: relevance for the development of pregnancy-induced hypertension? J Clin Endocrinol Metab 86:5222–5226

    PubMed  Google Scholar 

  • Hercz P, Kazy Z, Siklos P, Ungar L (1989) Quantitative comparison of serum steroid and peptide hormone concentrations in male and female fetuses in the maternal–fetoplacental system during the 28th–40th weeks of pregnancy. Eur J Obstet Gynecol Reprod Biol 30:201–204

    PubMed  Google Scholar 

  • Hirasawa G, Takeyama J, Sasano H, Fukushima K, Suzuki T, Muramatu Y, Darnel AD, Kaneko C, Hiwatashi N, Toyota T, Nagura H, Krozowski ZS (2000) 11Beta-hydroxysteroid dehydrogenase type II and mineralocorticoid receptor in human placenta. J Clin Endocrinol Metab 85:1306–1309

    Article  PubMed  Google Scholar 

  • Hodgson DM, Knott B (2002) Potentiation of tumor metastasis in adulthood by neonatal endotoxin exposure: sex differences. Psychoneuroendocrinology 27:791–804

    PubMed  Google Scholar 

  • Hodgson DM, Knott B, Walker FR (2001) Neonatal endotoxin exposure influences HPA responsivity and impairs tumor immunity in Fischer 344 rats in adulthood. Pediatr Res 50:750–755

    PubMed  Google Scholar 

  • Hunt JS (1989) Cytokine networks in the uteroplacental unit: macrophages as pivotal regulatory cells. J Reprod Immunol 16:1–17

    Article  PubMed  Google Scholar 

  • Jobe AH, Newnham J, Willet K, Sly P, Ikegami M (1998) Fetal versus maternal and gestational age effects of repetitive antenatal glucocorticoids. Pediatrics 102:1116–1125

    Article  PubMed  Google Scholar 

  • Jobe AH, Newnham JP, Moss TJ, Ikegami M (2003) Differential effects of maternal betamethasone and cortisol on lung maturation and growth in fetal sheep. Am J Obstet Gynecol 188:22–28

    Article  PubMed  Google Scholar 

  • Kajantie E, Dunkel L, Turpeinen U, Stenman UH, Wood PJ, Nuutila M, Andersson S (2003) Placental 11 beta-hydroxysteroid dehydrogenase-2 and fetal cortisol/cortisone shuttle in small preterm infants. J Clin Endocrinol Metab 88:493–500

    PubMed  Google Scholar 

  • Kirschbaum C, Kudielka BM, Gaab J, Schommer NC, Hellhammer DH (1999) Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus–pituitary–adrenal axis. Psychosom Med 61:154–162

    PubMed  Google Scholar 

  • Kos-Kudla B, Pluskiewicz W (1997) Quantitative ultrasound of the heel and serum and urinary cortisol values in assessment of long-term corticotherapy side effects in female bronchial asthma patients. Ultrasound Med Biol 23:1325–1330

    Article  PubMed  Google Scholar 

  • Kovar J, Waddell BJ, Sly PD, Willet KE (2001) Sex differences in response to steroids in preterm sheep lungs are not explained by glucocorticoid receptor number or binding affinity. Pediatr Pulmonol 32:8–13

    Article  PubMed  Google Scholar 

  • Kurinczuk JJ, Parsons DE, Dawes V, Burton PR (1999) The relationship between asthma and smoking during pregnancy. Women Health 29:31–47

    Article  Google Scholar 

  • Lagerstrom M, Bremme K, Eneroth P (1990) Maternal serum levels of estriol, prolactin, human placental lactogen and chorionic gonadotrophin related to fetal sex in normal and abnormal pregnancies. Gynecol Obstet Invest 30:198–203

    PubMed  Google Scholar 

  • Lao TT, Huengsburg M (1990) Labour and delivery in mothers with asthma. Eur J Obstet Gynecol Reprod Biol 35:183–190

    PubMed  Google Scholar 

  • Lappas M, Permezel M, Georgiou HM, Rice GE (2002) Nuclear factor kappa B regulation of proinflammatory cytokines in human gestational tissues in vitro. Biol Reprod 67:668–673

    Article  PubMed  Google Scholar 

  • Le Mevel JC, Abitbol S, Beraud G, Maniey J (1978) Dynamic changes in plasma adrenocorticotrophin after neurotropic stress in male and female rats. J Endocrinol 76:359–360

    PubMed  Google Scholar 

  • Lindsay RS, Lindsay RM, Waddell BJ, Seckl JR (1996) Prenatal glucocorticoid exposure leads to offspring hyperglycaemia in the rat: studies with the 11 beta-hydroxysteroid dehydrogenase inhibitor carbenoxolone. Diabetologia 39:1299–1305

    Article  PubMed  Google Scholar 

  • Lingas R, Dean F, Matthews SG (1999) Maternal nutrient restriction (48 h) modifies brain corticosteroid receptor expression and endocrine function in the fetal guinea pig. Brain Res 846:236–242

    PubMed  Google Scholar 

  • Lipworth BJ (1996) Airway and systemic effects of inhaled corticosteroids in asthma: dose response relationship. Pulm Pharmacol 9:19–27

    Article  PubMed  Google Scholar 

  • Liu S, Wen SW, Demissie K, Marcoux S, Kramer MS (2001) Maternal asthma and pregnancy outcomes: a retrospective cohort study. Am J Obstet Gynecol 184:90–96

    Article  PubMed  Google Scholar 

  • Maltau JM, Eielsen OV, Stokke KT (1979) Effect of stress during labor on the concentration of cortisol and estriol in maternal plasma. Am J Obstet Gynecol 134:681–684

    PubMed  Google Scholar 

  • McCormick CM, Smythe JW, Sharma S, Meaney MJ (1995) Sex-specific effects of prenatal stress on hypothalamic–pituitary–adrenal responses to stress and brain glucocorticoid receptor density in adult rats. Brain Res Dev Brain Res 84:55–61

    Article  PubMed  Google Scholar 

  • McCormick CM, Linkroum W, Sallinen BJ, Miller NW (2002) Peripheral and central sex steroids have differential effects on the HPA axis of male and female rats. Stress 5:235–247

    PubMed  Google Scholar 

  • McDonald CF, Burdon JG (1996) Asthma in pregnancy and lactation. A position paper for the Thoracic Society of Australia and New Zealand. Med J Aust 165:485–488

    PubMed  Google Scholar 

  • McDowell B, Evans SE, Weaver JB, Little D (1988) An assessment of the value of biochemical fetoplacental function tests in detecting intrauterine growth retardation. Ann Clin Biochem 25:264–270

    PubMed  Google Scholar 

  • McGregor JA, Leff M, Orleans M, Baron A (1992) Fetal gender differences in preterm birth: findings in a north American cohort. Am J Perinatol 9:43–48

    PubMed  Google Scholar 

  • McTernan CL, Draper N, Nicholson H, Chalder SM, Driver P, Hewison M, Kilby MD, Stewart PM (2001) Reduced placental 11beta-hydroxysteroid dehydrogenase type 2 mRNA levels in human pregnancies complicated by intrauterine growth restriction: an analysis of possible mechanisms. J Clin Endocrinol Metab 86:4979–4983

    PubMed  Google Scholar 

  • Misao R, Iwagaki S, Sun WS, Fujimoto J, Saio M, Takami T, Tamaya T (1999) Evidence for the synthesis of corticosteroid-binding globulin in human placenta. Horm Res 51:162–167

    PubMed  Google Scholar 

  • Moss TJ, Nitsos I, Kramer BW, Ikegami M, Newnham JP, Jobe AH (2002) Intra-amniotic endotoxin induces lung maturation by direct effects on the developing respiratory tract in preterm sheep. Am J Obstet Gynecol 187:1059–1065

    Article  PubMed  Google Scholar 

  • Murphy VE, Zakar T, Smith R, Giles WB, Gibson PG, Clifton VL (2002) Reduced 11beta-hydroxysteroid dehydrogenase type 2 activity is associated with decreased birth weight centile in pregnancies complicated by asthma. J Clin Endocrinol Metab 87:1660–1668

    Article  PubMed  Google Scholar 

  • Murphy VE, Gibson PG, Giles WB, Zakar T, Smith R, Bisits AM, Kessell CG, Clifton VL (2003) Maternal asthma is associated with reduced female fetal growth. Am J Respir Crit Care Med 168:1317–1323

    Article  PubMed  Google Scholar 

  • Odermatt A, Arnold P, Frey FJ (2001) The intracellular localization of the mineralocorticoid receptor is regulated by 11beta-hydroxysteroid dehydrogenase type 2. J Biol Chem 276:28484–28492

    Article  PubMed  Google Scholar 

  • Owen D, Matthews SG (2003) Glucocorticoids and sex-dependent development of brain glucocorticoid and mineralocorticoid receptors. Endocrinology 144:2775–2784

    PubMed  Google Scholar 

  • Papageorgiou AN, Colle E, Farri-Kostopoulos E, Gelfand MM (1981) Incidence of respiratory distress syndrome following antenatal betamethasone: role of sex, type of delivery, and prolonged rupture of membranes. Pediatrics 67:614–617

    PubMed  Google Scholar 

  • Parker CR Jr, Atkinson MW, Owen J, Andrews WW (1996) Dynamics of the fetal adrenal, cholesterol, and apolipoprotein B responses to antenatal betamethasone therapy. Am J Obstet Gynecol 174:562–565

    Article  PubMed  Google Scholar 

  • Patel FA, Sun K, Challis JR (1999) Local modulation by 11beta-hydroxysteroid dehydrogenase of glucocorticoid effects on the activity of 15-hydroxyprostaglandin dehydrogenase in human chorion and placental trophoblast cells. J Clin Endocrinol Metab 84:395–400

    Article  PubMed  Google Scholar 

  • Patrick J, Challis J, Natale R, Richardson B (1979) Circadian rhythms in maternal plasma cortisol, estrone, estradiol, and estriol at 34 to 35 weeks’ gestation. Am J Obstet Gynecol 135:791–798

    PubMed  Google Scholar 

  • Perlow JH, Montgomery D, Morgan MA, Towers CV, Porto M (1992) Severity of asthma and perinatal outcome. Am J Obstet Gynecol 167:963–967

    PubMed  Google Scholar 

  • Procianoy RS, Cecin SK (1986) Umbilical cord dehydroepiandrosterone sulfate and cortisol levels in preterm infants born to pre-eclamptic mothers. Acta Paediatr Scand 75:279–282

    PubMed  Google Scholar 

  • Procianoy RS, Giacomini CB, Oliveira ML (1988) Fetal and neonatal cortical adrenal function in birth asphyxia. Acta Paediatr Scand 77:671–674

    PubMed  Google Scholar 

  • Quinlivan JA, Archer MA, Dunlop SA, Evans SF, Beazley LD, Newnham JP (1998) Fetal growth retardation, particularly within lymphoid organs, following repeated maternal injections of betamethasone in sheep. J Obstet Gynaecol Res 24:173–182

    PubMed  Google Scholar 

  • Rabbitt EH, Gittoes NJ, Stewart PM, Hewison M (2003) 11Beta-hydroxysteroid dehydrogenases, cell proliferation and malignancy. J Steroid Biochem Mol Biol 85:415–421

    Article  PubMed  Google Scholar 

  • Rodriguez A, Viscardi RM, Torday JS (2001) Fetal androgen exposure inhibits fetal rat lung fibroblast lipid uptake and release. Exp Lung Res 27:13–24

    PubMed  Google Scholar 

  • Rosen T, Krikun G, Ma Y, Wang EY, Lockwood CJ, Guller S (1998) Chronic antagonism of nuclear factor-kappaB activity in cytotrophoblasts by dexamethasone: a potential mechanism for antiinflammatory action of glucocorticoids in human placenta. J Clin Endocrinol Metab 83:3647–3652

    Article  PubMed  Google Scholar 

  • Schatz M (1999) Interrelationships between asthma and pregnancy: a literature review. J Allergy Clin Immunol 103:S330–S336

    Article  PubMed  Google Scholar 

  • Schatz M, Zeiger RS, Hoffman CP, Harden K, Forsythe A, Chilingar L, Saunders B, Porreco R, Sperling W, Kagnoff M (1995) Perinatal outcomes in the pregnancies of asthmatic women: a prospective controlled analysis. Am J Respir Crit Care Med 151:1170–1174

    PubMed  Google Scholar 

  • Schatz M, Dombrowski MP, Wise R, Thom EA, Landon M, Mabie W, Newman RB, Hauth JC, Lindheimer M, Caritis SN, Leveno KJ, Meis P, Miodovnik M, Wapner RJ, Paul RH, Varner MW, O’Sullivan M J, Thurnau GR, Conway D, McNellis D (2003) Asthma morbidity during pregnancy can be predicted by severity classification. J Allergy Clin Immunol 112:283–288

    Article  PubMed  Google Scholar 

  • Schoof E, Girstl M, Frobenius W, Kirschbaum M, Dorr HG, Rascher W, Dotsch J (2001) Decreased gene expression of 11beta-hydroxysteroid dehydrogenase type 2 and 15-hydroxyprostaglandin dehydrogenase in human placenta of patients with preeclampsia. J Clin Endocrinol Metab 86:1313–1317

    PubMed  Google Scholar 

  • Schuurs AH, Verheul HA (1990) Effects of gender and sex steroids on the immune response. J Steroid Biochem 35:157–172

    Article  PubMed  Google Scholar 

  • Seckl JR (2004) Prenatal glucocorticoids and long-term programming. Eur J Endocrinol 151 (Suppl 3):U49–U62

    PubMed  Google Scholar 

  • Seckl JR, Walker BR (2001) Minireview: 11beta-hydroxysteroid dehydrogenase type 1—a tissue-specific amplifier of glucocorticoid action. Endocrinology 142:1371–1376

    Article  PubMed  Google Scholar 

  • Shams M, Kilby MD, Somerset DA, Howie AJ, Gupta A, Wood PJ, Afnan M, Stewart PM (1998) 11Beta-hydroxysteroid dehydrogenase type 2 in human pregnancy and reduced expression in intrauterine growth restriction. Hum Reprod 13:799–804

    Article  PubMed  Google Scholar 

  • Shanks N, McCormick CM, Meaney MJ (1994) Sex differences in hypothalamic–pituitary–adrenal responding to endotoxin challenge in the neonate: reversal by gonadectomy. Brain Res Dev Brain Res 79:260–266

    Article  PubMed  Google Scholar 

  • Siiteri PK, MacDonald PC (1966) Placental estrogen biosynthesis during human pregnancy. J Clin Endocrinol Metab 26:751–761

    PubMed  Google Scholar 

  • Simmons D, France JT, Keelan JA, Song L, Knox BS (1994) Sex differences in umbilical cord serum levels of inhibin, testosterone, oestradiol, dehydroepiandrosterone sulphate, and sex hormone-binding globulin in human term neonates. Biol Neonate 65:287–294

    PubMed  Google Scholar 

  • Sloboda DM, Newnham JP, Challis JR (2000) Effects of repeated maternal betamethasone administration on growth and hypothalamic–pituitary–adrenal function of the ovine fetus at term. J Endocrinol 165:79–91

    Article  PubMed  Google Scholar 

  • Smith JT, Waddell BJ (2000) Increased fetal glucocorticoid exposure delays puberty onset in postnatal life. Endocrinology 141:2422–2428

    Article  PubMed  Google Scholar 

  • Stevenson DK, Verter J, Fanaroff AA, Oh W, Ehrenkranz RA, Shankaran S, Donovan EF, Wright LL, Lemons JA, Tyson JE, Korones SB, Bauer CR, Stoll BJ, Papile LA (2000) Sex differences in outcomes of very low birthweight infants: the newborn male disadvantage. Arch Dis Child Fetal Neonatal Ed 83:F182–F185

    Article  PubMed  Google Scholar 

  • Sweezey NB, Ghibu F, Gagnon S, Schotman E, Hamid Q (1998) Glucocorticoid receptor mRNA and protein in fetal rat lung in vivo: modulation by glucocorticoid and androgen. Am J Physiol 275:L103–L109

    PubMed  Google Scholar 

  • Tangalakis K, Crawford R, McFarlane AC, Wintour EM (1994) Regulation of steroid hydroxylase gene expression in the ovine fetal adrenal gland at 0.4 gestation. Mol Cell Endocrinol 103:21–27

    Article  PubMed  Google Scholar 

  • Troisi R, Potischman N, Roberts J, Siiteri P, Daftary A, Sims C, Hoover RN (2003a) Associations of maternal and umbilical cord hormone concentrations with maternal, gestational and neonatal factors (United States). Cancer Causes Control 14:347–355

    Article  PubMed  Google Scholar 

  • Troisi R, Potischman N, Roberts JM, Harger G, Markovic N, Cole B, Lykins D, Siiteri P, Hoover RN (2003b) Correlation of serum hormone concentrations in maternal and umbilical cord samples. Cancer Epidemiol Biomarkers Prev 12:452–456

    PubMed  Google Scholar 

  • Vatten LJ, Skjaerven R (2004) Offspring sex and pregnancy outcome by length of gestation. Early Hum Dev 76:47–54

    Article  PubMed  Google Scholar 

  • Warnes KE, Morris MJ, Symonds ME, Phillips ID, Clarke IJ, Owens JA, McMillen IC (1998) Effects of increasing gestation, cortisol and maternal undernutrition on hypothalamic neuropeptide Y expression in the sheep fetus. J Neuroendocrinol 10:51–57

    Article  PubMed  Google Scholar 

  • Wegmann TG, Guilbert LJ (1992) Immune signalling at the maternal–fetal interface and trophoblast differentiation. Dev Comp Immunol 16:425–430

    Article  PubMed  Google Scholar 

  • Wegmann TG, Lin H, Guilbert L, Mosmann TR (1993) Bidirectional cytokine interactions in the maternal–fetal relationship: is successful pregnancy a TH2 phenomenon? Immunol Today 14:353–356

    Article  PubMed  Google Scholar 

  • Weinberg J, Petersen TD (1991) Effects of prenatal ethanol exposure on glucocorticoid receptors in rat hippocampus. Alcohol Clin Exp Res 15:711–716

    PubMed  Google Scholar 

  • Weinstock M, Matlina E, Maor GI, Rosen H, McEwen BS (1992) Prenatal stress selectively alters the reactivity of the hypothalamic–pituitary adrenal system in the female rat. Brain Res 595:195–200

    Article  PubMed  Google Scholar 

  • Wenzel S (2003) Mechanisms of severe asthma. Clin Exp Allergy 33:1622–1628

    Article  PubMed  Google Scholar 

  • Wilcoxon JS, Schwartz J, Aird F, Redei EE (2003) Sexually dimorphic effects of maternal alcohol intake and adrenalectomy on left ventricular hypertrophy in rat offspring. Am J Physiol Endocrinol Metab 285:E31–E39

    PubMed  Google Scholar 

  • Wintour EM, Alcorn D, McFarlane A, Moritz K, Potocnik SJ, Tangalakis K (1994) Effect of maternal glucocorticoid treatment on fetal fluids in sheep at 0.4 gestation. Am J Physiol 266:R1174–R1181

    PubMed  Google Scholar 

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Clifton, V.L. Sexually dimorphic effects of maternal asthma during pregnancy on placental glucocorticoid metabolism and fetal growth. Cell Tissue Res 322, 63–71 (2005). https://doi.org/10.1007/s00441-005-1117-5

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