Altered expression of IGFs and IGF-binding proteins during intrauterine growth restriction in guinea pigs

Carter, Anthony Michael; Kingston, M.J.; Han, Kyu‐Ho; Mazzuca, Delfina M.; Nygard, Karen; Han, V. K. M.

doi:10.1677/joe.1.05781

Cited by 43 publications

(26 citation statements)

References 47 publications

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“…Reported data on the possible effects of hypoxia on IGFBP-2 are contrasting (32). We detected a significant increase in cord serum IGFBP-2 in FGR newborns, but the mechanisms underlying this observation are unknown.…”

Section: Discussionmentioning

confidence: 65%

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Changes in interleukin-6 and IGF system and their relationships in placenta and cord blood in newborns with fetal growth restriction compared with controls

et al. 2006

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Objectives: The IGF system is central to fetal growth. Recently, the relationships between cytokines and the IGF system have been shown in specific tissues. It is unknown whether these occur in the placenta. The aim of this study was to assess whether interleukin-6 (IL-6) modulated the IGF system. Methods: Whole villous tissue and cord serum were collected from fetal growth restriction (FGR) neonates diagnosed before birth with altered Doppler velocimetry and controls. Sixteen FGR and 20 controls, born after week 32 of gestation from elective Caesarean sections, were compared. Total RNA was extracted from the placenta samples, reverse transcribed, and real-time quantitative reverse transcriptase (RT)-PCR was performed to quantify cDNA for IGF-I, IGF-II, IGF binding protein (IGFBP)-1, IGFBP-2, and IL-6. The same proteins were assayed in placenta lysates and cord serum using specific commercial kits and western immunoblotting. Results: FGR subjects had significantly more IGFBPs-1 and -2, and IL-6 mRNA and corresponding proteins in the placenta. In particular, the less phosphorylated isoforms of IGFBP-1 were highly increased. IL-6 and IGFBPs-2 mRNA, and IL-6 and IGFBP-1 peptides were positively and significantly correlated in the placenta. The IGF-II peptide was also significantly increased in FGR placentas. In cord serum, IGFBPs-1 and -2 were significantly more elevated in the FGR neonates. Serum IL-6 was significantly and positively correlated with both IGFBP-1 and IGFBP-2. Conclusions: The placenta of FGR neonates has higher IGF-II, IGFBP-1, IGFBP-2, and IL-6 contents compared with controls. At birth, IGFBPs-1 and -2 are increased in the cord blood of FGR neonates. IL-6 and IGFBP-2 gene expressions are closely related in the placenta. We suggest that the increase in IL-6 and IGFBP-2 could be subsequent to hypoxia and nutrient deficiency. As IGFBP-2 has a strong affinity for IGF-II, which is crucial for fetal growth, it could be an important bioregulator of IGF-II in the placenta.European Journal of Endocrinology 155 567-574

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Section: Discussionmentioning

confidence: 65%

“…Data in growth-restricted guinea pigs from uterine artery ligation confirm unchanged IGF-II mRNA in the placenta (32). There are no data in humans with which we can make comparisons.…”

Section: Discussionmentioning

confidence: 92%

Changes in interleukin-6 and IGF system and their relationships in placenta and cord blood in newborns with fetal growth restriction compared with controls

et al. 2006

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“…The guinea pig has previously been used as an animal model for studying IUGR and lung injury associated with prematurity (17)(18)(19)(20). Unlike other laboratory rodents, the guinea pig has a long gestational period.…”

Section: Articlesmentioning

confidence: 99%

“…To better understand these mechanisms, an animal model is required to allow the investigation of systems controlling microvascular blood flow because such studies are not possible in the human neonate. Little evidence of the mechanisms controlling The guinea pig has previously been used as an animal model for studying IUGR and lung injury associated with prematurity (17)(18)(19)(20). Unlike other laboratory rodents, the guinea pig has a long gestational period.…”

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confidence: 99%

The guinea pig as an animal model for studying perinatal changes in microvascular function

et al. 2011

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INTRODUCTION: Microvascular dysfunction, characterized by inappropriate vasodilatation and high blood flow in the peripheral microcirculation, is linked to physiologic instability and poor outcome in neonates. specifically, preterm neonates have significantly higher levels of baseline microvascular blood flow than term neonates at 24 h postnatal age. Because of similarities between human and guinea pig endocrine profiles and maturity at birth, we hypothesized that preterm guinea pig neonates would provide a suitable model for studying the mechanisms underlying transitional microvascular function. RESULTS: Guinea pigs that were delivered preterm showed immaturity and had markedly reduced viability. Baseline microvascular blood flow was significantly higher in preterm animals than in term animals. No effect of intrauterine growth restriction or birth weight on baseline microvascular blood flow was observed in either preterm or term animals. DISCUSSION: These results are consistent with recent clinical findings and support the use of the guinea pig as a suitable model for future studies of the mechanisms underlying perinatal microvascular behavior. METHODS: Guinea pigs were delivered either prematurely or at term. Laser Doppler flowmetry was used to study microvascular blood flow at 23 h postnatal age. In term infants, the circulation undergoes rapid and extensive changes in the initial hours of extrauterine life to allow the infant to effectively deal with extrauterine systemic vascular resistance and hence provide normal and adequate perfusion of tissues (1-3). The transitional circulation of preterm neonates (especially those born at ≤30 wk gestation) differs significantly from infants born at full term. In the preterm infant, several crucial physiologic responses to extrauterine life are commonly delayed, allowing for persistence of atrial and ductal shunting and inappropriate blood flow throughout the periphery during the perinatal period (4)(5)(6)(7)(8).Previous studies in preterm infants suggest that abnormal microvascular tone, characterized by inappropriate vasodilatation of the peripheral microvasculature, may contribute to the development of circulatory compromise (4,8). These studies found that the functional integrity of the microvasculature (including appropriate control of vasodilatation) in preterm neonates is significantly altered as compared with neonates born at later gestational ages (GAs). Very preterm neonates (born at 24-28 wk GA) are known to have significantly higher microvascular blood flow at 24 h postnatal age than preterm neonates born at 29-34 wk GA and neonates born at term. High baseline microvascular blood flow in premature infants is significantly correlated with clinical illness severity and poor outcome in the immediate postnatal period (4,9). Such dysfunction in the microvasculature is also a well-established observation associated with the onset of other causes of multisystem organ failure in neonates (10).In addition to disorders relating to short gestation, intrauterine growt...

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“…Regulation and function of placental IGFBP-1 differs from species to species. For example, guinea pig and murine decidua do not normally express IGFBP-1 [47,48], and sheep have non-deciduate placentae in which IGFBP-3 exerts paracrine-autocrine regulation [49]. These differences have overt consequences.…”

Section: Igfbp-1 and Igfbp-3mentioning

confidence: 99%

The IGF Axis in Baboon Pregnancy: Placental and Systemic Responses to Feeding 70% Global Ad Libitum Diet

Li¹,

Levitz²,

Hubbard³

et al. 2007

Placenta

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Information on the influence of poor maternal nutrition on the regulation of responses to pregnancy, placental and fetal growth and development is critical to a better understanding of pregnancy physiology and pathophysiology. We determined normal changes and effects of controlled and monitored moderate nutrient restriction (NR) (global nutrient intake reduced to 70% of food consumed by mothers feeding ad libitum from 0.16 to 0.5 of gestation) in the baboon, on important hematological, biochemical, and hormonal indices of fetal growth and placental function. Serum IGF-I:IGFBP-3 ratio was lower in pregnant than control non-pregnant baboons feeding ad libitum. Serum concentrations of total and free IGF-I were decreased in NR mothers compared with controls (p < 0.05). The decrease in fetal IGF-I did not reach significance (p = 0.057). Serum IGF-I: IGFBP-3 ratio was decreased by NR in both mothers and fetuses. Maternal serum IGF-II was unchanged by NR. Placental IGF-I mRNA and protein abundance were similarly reduced whereas IGF-II mRNA increased in placental tissue of NR compared to control mothers. Systemic (maternal) and local (placental) IGFBP-1 and IGFBP-3 mRNA and protein abundance were unchanged by NR. Type 1 IGF receptor protein in the syncytiotrophoblast increased in NR. Type 2 IGF receptor protein was present in the stem villi core, and decreased after NR. We conclude that moderate NR in this important non-human primate model significantly disrupts the maternal and placental IGF-IGFBP axis and influences placental expression of this key system at the gene and protein level. Changes observed appear to be directed toward preserving placental growth.

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Altered expression of IGFs and IGF-binding proteins during intrauterine growth restriction in guinea pigs

Cited by 43 publications

References 47 publications

Changes in interleukin-6 and IGF system and their relationships in placenta and cord blood in newborns with fetal growth restriction compared with controls

Changes in interleukin-6 and IGF system and their relationships in placenta and cord blood in newborns with fetal growth restriction compared with controls

The guinea pig as an animal model for studying perinatal changes in microvascular function

The IGF Axis in Baboon Pregnancy: Placental and Systemic Responses to Feeding 70% Global Ad Libitum Diet

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