Fetal Hypothalamic-Pituitary Adrenal (HPA) Development and Activation as a Determinant of the Timing of Birth, and of Postnatal Disease

Challis, J; Sloboda, D.M.; Matthews, Sharon; Holloway, A.; Alfaidy, Nadia; Howe, David; Fraser, Mhoyra; Newnham, John P.

doi:10.3109/07435800009048560

Cited by 65 publications

(58 citation statements)

References 2 publications

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“…Of particular note, prostaglandins can stimulate HSD11B1 activity in the placenta and glucocorticoids increase prostaglandin synthesis by upregulating expression and activities of phospholipase A2 and PTGS2 (see Ref. 63), thereby establishing a positive feedforward loop implicated in the timing of parturition (13). Therefore, HSD11B1 may be involved in the production of prostaglandins by the ovine endometrium during early pregnancy as well as the local production of cortisol in bovine endometrium (53).…”

Section: Discussionmentioning

confidence: 99%

“…The postovulatory rise in circulating P4 during early pregnancy clearly affects blastocyst growth in cattle (60). Increasing concentrations of P4 during metestrus and early diestrus enhanced blastocyst development and size by days [13][14][15][16] in heifers and cows (12,23,59), while animals with lower concentrations of P4 in the early luteal phase had retarded embryonic development (61,66) and conceptuses produced less IFNT (61). Studies of both sheep and cattle are beginning to identify pregnancy and P4-responsive genes in the endometrium that potentially regulate blastocyst elongation and implantation of the conceptus (see Refs.…”

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confidence: 99%

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Discovery of candidate genes and pathways in the endometrium regulating ovine blastocyst growth and conceptus elongation

Satterfield

Song

Kochan

et al. 2009

Physiological Genomics

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Establishment of pregnancy in ruminants requires blastocyst growth to form an elongated conceptus that produces interferon tau, the pregnancy recognition signal, and initiates implantation. Blastocyst growth and development requires secretions from the uterine endometrium. An early increase in circulating concentrations of progesterone (P4) stimulates blastocyst growth and elongation in ruminants. This study utilized sheep as a model to identify candidate genes and regulatory networks in the endometrium that govern preimplantation blastocyst growth and development. Ewes were treated daily with either P4 or corn oil vehicle from day 1.5 after mating to either day 9 or day 12 of pregnancy when endometrium was obtained by hysterectomy. Microarray analyses revealed many differentially expressed genes in the endometria affected by day of pregnancy and early P4 treatment. In situ hybridization analyses revealed that many differentially expressed genes were expressed in a cell-specific manner within the endometrium. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to identify functional groups of genes and biological processes in the endometrium that are associated with growth and development of preimplantation blastocysts. Notably, biological processes affected by day of pregnancy and/or early P4 treatment included lipid biosynthesis and metabolism, angiogenesis, transport, extracellular space, defense and inflammatory response, proteolysis, amino acid transport and metabolism, and hormone metabolism. This transcriptomic data provides novel insights into the biology of endometrial function and preimplantation blastocyst growth and development in sheep.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Discovery of candidate genes and pathways in the endometrium regulating ovine blastocyst growth and conceptus elongation

Satterfield

Song

Kochan

et al. 2009

Physiological Genomics

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“…early rodent studies (Gardner et al 1998) to later large animal models (Challis et al 2000, Edwards et al 2001a, Bloomfield et al 2004), a role for increased GC exposure or altered regulation of the HPA axis in fetal through to adult life, after variations in the maternal diet, has been proposed and intensively studied. However, for a number of reasons outlined below, a causal relationship has proved difficult to ascertain.…”

Section: Discussionmentioning

confidence: 99%

Effect of periconceptional undernutrition and gender on hypothalamic–pituitary–adrenal axis function in young adult sheep

Gardner¹,

Bon²,

Dandrea

et al. 2006

Journal of Endocrinology

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Glucocorticoids are proposed to act as intermediary factors that transcribe the developmental programming sequelae of maternal nutrient restriction (NR). Periconceptional undernutrition of sheep markedly activates fetal hypothalamicpituitary-adrenal (HPA) axis activity leading to preterm birth, while transient undernutrition during late gestation in sheep programs adult HPA axis function. To date, no study has examined resting or stimulated HPA axis function in young adult offspring following a periconceptional nutritional challenge. In the present study, 20 ewes were either periconceptionally undernourished (50% metabolisable energy requirements from days 1 to 30 gestation; NR, nZ8) or fed to control levels (100% requirement; controls, nZ12) to term (147 days gestation). Ewes were blood sampled remotely at 2 and 30 days using automated blood sampling equipment. Thereafter, offspring (controls, nZ6/6 males/females; NR, nZ4/4 males/females) were reared to 1 year of age and on separate days received either an i.v. corticotrophin-releasing hormone (CRH; 0$5 mg/kg) and vasopressin (AVP; 0$1 mg/kg) challenge or a synthetic ACTH i.v. bolus (Synacthen; 1$25 mg/kg), and blood samples were taken (manually and remotely) at appropriate intervals for measurement of plasma ACTH and cortisol accordingly. Resting plasma cortisol, assessed remotely, was similar in ewes during undernutrition (control 18$3G1$4 vs NR 23$4G1$9 nmol/l) and in offspring at 4 months of age (control male 17$6G2$9; control female 17$2G0$4, NR male 16$5G3$1, NR female 21$7G4$0 nmol/l). At 12 months of age, however, resting plasma cortisol was significantly increased in NR females (control male 28$0G1$5, control female 32$9G9, NR male 32G7, NR female 53G10 nmol/l, F 5$7, PZ0$02) despite no difference in plasma ACTH concentration. There was an interaction between nutritional group and gender for both the pituitary and adrenal responses to CRH and AVP, i.e. for controls, females exhibited increased plasma ACTH or cortisol relative to males but for NR this trend was either not present or reversed. The adrenocortical response to synthetic ACTH was gender-dependent only, being greater in female offspring. Combined CRH and AVP provoked a transient hypertension and marked bradycardia in all animals, irrespective of dietary group or gender and could be effectively reproduced by an AVP bolus alone. In conclusion, the present study has shown that periconceptional undernutrition of sheep has only a minor influence on HPA axis function in their young adult offspring when considered alongside the effect of gender per se.

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“…IN MOST ANIMAL SPECIES birth is triggered through the activation of the fetal hypothalamic-pituitary-adrenal axis (HPAA), whereas preterm birth may be associated with precocious activation of this axis (5). Despite the existence of a functional negative feedback mechanism in the fetal HPAA at 121-131 days gestation, plasma adrenocorticotrophin (ACTH) and cortisol concentrations rise progressively in a semilogarithmic pattern in the last 15-20 days of gestation (14,(32)(33)(34).…”

mentioning

confidence: 99%

Effects of periconceptional undernutrition on the initiation of parturition in sheep

Kumarasamy

Mitchell²,

Bloomfield³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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In sheep, parturition is initiated by increased fetal hypothalamic-pituitary-adrenal axis (HPAA) activity leading to PGE2 and PGF2␣ production and a rise in the 17␤-estradiol-progesterone (E 2/P4) ratio. Uteroplacental PG production can also increase fetal HPAA activity. Periconceptional maternal undernutrition accelerates fetal HPAA maturation resulting in preterm labor. We determined whether preterm labor was preceded by an increase in PG concentrations and E 2/P4 ratio and whether these increases preceded or followed the corresponding rise in cortisol concentrations. Singleton-bearing ewes were nourished ad libitum (N, n ϭ 9) or undernourished (UN, n ϭ 10) to reduce maternal weight by 15% from Ϫ61 days (d) to ϩ30 d after mating with ad libitum intake thereafter. Paired maternal and fetal blood samples were collected from 126 d until delivery. Half the UN group delivered prematurely (Ͼ2 SD below mean gestation for the flock). PG and cortisol concentrations and E 2/P4 ratio increased before delivery in the same way in both groups. However, the increases occurred 7-10 d earlier in UN than in N animals. In both UN and N fetuses cortisol concentrations rose before fetal and maternal PG concentrations and maternal E 2/P4 ratio. Periconceptional maternal undernutrition induces preterm delivery in sheep by advancing the expected prepartum rise in cortisol and PG concentrations and E 2/P4 ratio. The rise in fetal cortisol concentration precedes the rise in fetal and maternal PG concentrations and maternal E 2/P4 ratio, suggesting that the underlying mechanism is likely to be acceleration of fetal HPAA maturation, resulting in initiation of the normal process of parturition.hypothalamic-pituitary-adrenal axis; prostaglandin; cortisol; estrogenprogesterone ratio

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Fetal Hypothalamic-Pituitary Adrenal (HPA) Development and Activation as a Determinant of the Timing of Birth, and of Postnatal Disease

Cited by 65 publications

References 2 publications

Discovery of candidate genes and pathways in the endometrium regulating ovine blastocyst growth and conceptus elongation

Discovery of candidate genes and pathways in the endometrium regulating ovine blastocyst growth and conceptus elongation

Effect of periconceptional undernutrition and gender on hypothalamic–pituitary–adrenal axis function in young adult sheep

Effects of periconceptional undernutrition on the initiation of parturition in sheep

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