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Nutritional status before and during pregnancy in relation to the maternal insulin-like growth factor-system and health related variables in the offspring
Linköping University, Department of Biomedicine and Surgery, Nutrition. Linköping University, Faculty of Health Sciences.
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Adequate fetal growth is of importance for health in adulthood. Maternal nutritional status has been suggested to be one major factor influencing fetal development. The nature of how the mother's nutritional status and her metabolic, endocrine and physiological adaptations to pregnancy interact and how these interactions affect fetal growth is unclear. The insulin-like growth factor (IOF)-system has been suggested to be one mediator between maternal nutritional status and fetal growth. Impaired fetal growth may have life-long effects, but little is known about the possibilities to ameliorate intrauterine perturbations postnatally. Oxytocin, an anti-stress hormone, was used as a model to study such possibilities.

The aims were: to measure serum levels of IGF-I, IGF-II, IGF-binding protein (IGFBP)-1, IGFBP-3 and protease activity against IOFBP-3 in healthy women before, during and after pregnancy; to study the relationships regarding maternal body weight and composition before and during pregnancy versus components of the maternal IGF-system in serum in healthy women; to study the relationships regarding components of the maternal IGF-system in serum versus infant birth weight; to measure the expression of mRNA for IGF-I and IGF-II in different tissues in guinea pigs and to study how these expressions are altered by gestation and food restriction; to study long-term effects of maternal food restriction during gestation on health related variables in adult rat offspring; to study long-term effects of early postnatal treatment of oxytocin in the adult rat offspring.

Healthy women were studied before pregnancy, in weeks 8, 14, 20, 32, 35 of pregnancy and 2 weeks postpartum. Body weight, body composition and serum levels of IGF-I, IGF-II, IGFBP-1, IGFBP-3 and protease activity against IOFBP-3 were measured. Infant body weight and length at birth were obtained from hospital records. The amounts of mRNA for IGF-I and IGF-II in the liver, adipose tissues, muscles, spleen, uterus and placenta were measured in virginal and pregnant guinea pigs, being either ad libitum fed or food restricted. Rat dams were either ad libitum fed or food restricted during gestation. Their offspring received oxytocin or NaCI at day 1-14 of age. Blood pressure, plasma levels of corticosterone, IGF-1, IGFBP-1, and reproductive performance were measured in the adult offspring.

All of the studied components of the IGF-system in serum underwent changes during pregnancy. The levels of IGF-1 were reduced in early pregnancy compared to before conception. The lower the body weight or the less amount of body fat before pregnancy, the larger the decrease in IGF-I in early pregnancy. The combination of body weight before pregnancy and the serum level of IGF-I in early pregnancy explained as much as 47 % of the variation in birth weight, indicating that the higher the maternal body weight before pregnancy and the lower the level of IGF-I in early pregnancy, the heavier the infant. From week 20 of pregnancy, maternal levels of IGFBP-I were negatively correlated to birth weight. In late pregnancy, the abundance of IGFBP-I and protease activity in serum together explained 35% of the variation in birth weight, indicating that the lower the IGFBP-I and the higher the protease activity, the higher the birth weight. In guinea pigs, mRNA for IGF-I was expressed in high amounts in adipose tissue and liver, whereas mRNA for IGF-II were highly expressed in placenta and liver. The expression of IGF-I was in general unaffected by food restriction, but doubled during gestation, whereas the expression of IGF-II in the placenta was decreased by food restriction and increased in the liver by gestation. Maternal food restriction during gestation caused increased levels of corticosterone, IGF-I and IGFBP-I, but no elevation in blood pressure, in adult offspring. Early postnatal oxytocin treatment decreased blood pressure and corticosterone, whereas the influence on reproductive performance was dependent on the nutritional status of their dams and the current nutritional experience in adulthood.

In conclusion, this thesis confirms that the IGF-system may be one factor mediating the effects of maternal nutritional status on fetal growth. It also supports the suggestion that IGFBP-I in maternal serum may be used as a marker of infant birth weight. Adipose tissue was shown to produce high amounts of IGF-I, indicating endocrine functions during gestation. Postnatal oxytocin treatment ameliorated some of the adverse effects in adult offspring, induced by maternal food restriction.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 2004. , 66 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 860
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-23979Local ID: 3530ISBN: 91-7373-835-2 (print)OAI: oai:DiVA.org:liu-23979DiVA: diva2:244295
Public defence
2004-10-08, Hälsans Hus, Hälsouniversitetet, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-10-31Bibliographically approved
List of papers
1. A longitudinal study of the insulin-like growth factor system before, during and after pregnancy in healthy women
Open this publication in new window or tab >>A longitudinal study of the insulin-like growth factor system before, during and after pregnancy in healthy women
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

The maternal insulin-like growth factor (IGF)-system is considered to influence fetal growth. In this longitudinal study of 23 healthy women we aimed 1) to assess maternal serum levels of IGF-I, IGF-II, IGF binding protein (IGFBP)-1, IGFBP-3 and protease activity against IGFBP-3 before, during and after pregnancy, and 2) to relate these levels in early and late pregnancy to fetal and birth weight. Serum was collected before pregnancy, in weeks 8, 14, 20, 32 and 35 of pregnancy and 2 weeks postpartum. IGF-I, IGF-II, IGFBP-1, and IGFBP-3 were analyzed with radioimmuno/radiometric assays and protease activity with Western blot. Fetal weight was measured by means of ultrasound (week 31 of pregnancy) and birth weight was recorded. IGF-I was initially decreased during pregnancy, compared to before conception. This early decrease was not correlated with fetal or birth weight. In late pregnancy, IGF-I and protease activity were positively related to fetal weight, whereas from week 20 of pregnancy IGFBP-1 showed an inverse association with birth weight. We suggest that in healthy pregnant women there is a fine-tuned balance within the maternal IGF-system, with components With either promoting or restricting influences on fetal growth. The results indicate that maternal IGFBP-1 cguld be used from mid-pregnancy as a marker for birth weight.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-85045 (URN)
Available from: 2012-10-31 Created: 2012-10-31 Last updated: 2012-10-31
2. Maternal serum levels of insulin-like growth factor (IGF)-I and IGF binding protein-1 before and during pregnancy in relation to body weight and composition of mother and infant
Open this publication in new window or tab >>Maternal serum levels of insulin-like growth factor (IGF)-I and IGF binding protein-1 before and during pregnancy in relation to body weight and composition of mother and infant
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Objectives: To investigate the following relationships: 1) maternal body weight and composition versus insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-1 in maternal serum before and during pregnancy, and 2) IGF-I and IGFBP-1 in maternal serum during pregnancy versus infant birth weight, body composition and ponderal index.

Study design: Serum was collected from 23 healthy women before pregnancy, and in weeks 14, 32 and 35 of pregnancy. On these occasions maternal body weight and composition were assessed. Weight, length and body composition of the newborn were measured. Linear and multiple linear regression analyses were applied.

Results: Women with the lowest body weight and body fat content had the largest decreases in IGF-I in early pregnancy. During pregnancy maternal fat-free body weight was positively related to IGF-I, whereas body fat was inversely related to IGFBP-1. Maternal body weight before pregnancy and IGF-I in week 14 of gestation explained 47 % of the variation in birth weight.

Conclusion: The maternal IGF-system may be a mediator of the effect of maternal nutritional status on fetal growth.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-85046 (URN)
Available from: 2012-10-31 Created: 2012-10-31 Last updated: 2012-10-31
3. Effects of food restriction and pregnancy on the expression of insulin-like growth factors-I and -II in tissues from guinea pigs
Open this publication in new window or tab >>Effects of food restriction and pregnancy on the expression of insulin-like growth factors-I and -II in tissues from guinea pigs
2003 (English)In: Journal of Endocrinology, ISSN 0022-0795, E-ISSN 0022-0795, Vol. 179, no 3, 437-445 p.Article in journal (Refereed) Published
Abstract [en]

The insulin-like growth factor (IGF) system is subjected to pregnancy-associated changes in the circulation and is suggested to be of importance for partitioning of nutrients between the mother and the foetus. Interestingly, maternal undernutrition alters the pregnancy-associated changes, with possible adverse consequences for the mother and the foetus. However, it is not known how malnutrition and pregnancy alter the expression of mRNA for IGFs locally in different tIssues. The aims of this study were to investigate where IGF-I and IGF-II are expressed in guinea pigs and how this expression is altered during food restriction and pregnancy. Ad libitum-fed and food-restricted (fed 70% of the ad libitum-fed intake four weeks before pregnancy and throughout the study) guinea pigs were mated. On day 40 of pregnancy and on the corresponding day for virginal females the animals were killed. mRNA for IGF-I and IGF-II was analysed in various organs/tIssues by solution hybridisation. mRNA for IGF-I was expressed in high amounts in uterus, liver and adipose tIssues. The expression was not affected by food restriction, but was increased in liver and adipose tIssue and decreased in uterus by pregnancy. mRNA for IGF-II was expressed in high amounts in the placenta and liver. In the placenta the expression was decreased by food restriction. Pregnancy increased the levels of mRNA for IGF-II in the liver. Food-restricted dams had smaller foetuses and placentas. In conclusion, this study indicates an important role for the adipose tIssue during gestation, not only as an energy store but also as an endocrine tIssue expressing IGF-I. The decreased expression of IGF-II in the placenta due to food restriction is suggested to have adverse effects on placental structure and function.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25312 (URN)10.1677/joe.0.1790437 (DOI)9753 (Local ID)9753 (Archive number)9753 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-10-31
4. Postnatal oxytocin alleviates adverse effects in adult rat offspring caused by maternal malnutrition
Open this publication in new window or tab >>Postnatal oxytocin alleviates adverse effects in adult rat offspring caused by maternal malnutrition
2003 (English)In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 284, no 3, E475-E480 p.Article in journal (Refereed) Published
Abstract [en]

Repeated oxytocin administration to adult rats causes a long-term decrease of plasma levels of corticosterone and blood pressure and stimulates growth and fat retention. Maternal undernutrition increases blood pressure and plasma corticosterone in adult offspring. We hypothesized that oxytocin treatment early in life would alleviate adverse effects of intrauterine food restriction. Male pups from ad libitum-fed and food-restricted (fed 60% of ad libitum intake) dams were injected with oxytocin or saline in days 1–14 after birth. At 4 mo, blood pressure, plasma levels of corticosterone, and adiposity were assessed. Oxytocin treatment decreased blood pressure independently of nutrition, whereas the increased plasma levels of corticosterone were lowered to normal levels in food-restricted offspring. Blood pressure and adiposity were not affected by in utero food restriction, whereas birth and adult weight were. In conclusion, postnatal events may alleviate adverse effects caused by in utero food restriction. In contrast to more severe food restriction, a moderate general food restriction during gestation had no effect on blood pressure in the offspring.

Keyword
food restriction in utero, programming, blood pressure, plasma levels of corticosterone
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-47818 (URN)10.​1152/​ajpendo.​00297.​2002 (DOI)12556348 (PubMedID)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2012-10-31
5. Maternal food restriction during gestation elevates insulin-like growth factor I and insulin-like growth factor binding protein 1 in adult male rat offspring
Open this publication in new window or tab >>Maternal food restriction during gestation elevates insulin-like growth factor I and insulin-like growth factor binding protein 1 in adult male rat offspring
Show others...
2006 (English)In: Nutrition Research, ISSN 0271-5317, E-ISSN 1879-0739, Vol. 26, no 7, 350-355 p.Article in journal (Refereed) Published
Abstract [en]

Low birth weight due to maternal malnutrition is associated with increased risk of developing diseases in adulthood, for example, cardiovascular disease. Postnatal oxytocin treatment has previously been shown to have positive effects on blood pressure and corticosterone levels in adult offspring from malnourished dams. The aims of this study were to investigate if maternal food restriction during gestation alters plasma levels of insulin-like growth factor I (IGF-I), IGF binding protein 1 (IGFBP-1), glucose, and insulin in adult male rat offspring, and if postnatal oxytocin treatment has any effect on those changes. Adult offspring from food-restricted mothers had increased levels of IGF-I and IGFBP-1 compared with ad libitum–fed offspring. Postnatal oxytocin treatment had no effect on the IGF system in adulthood. In conclusion, maternal malnutrition during gestation altered the IGF system in adult rat offspring.

Keyword
IGF-I and IGFBP-1, Malnutrition, Programming, Rat, Undernutrition
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-50195 (URN)10.1016/j.nutres.2006.06.007 (DOI)
Note

Published article based from a manuscript entitled "Effects of maternal food restriction and postnatal oxytocin treatment on insulin-like growth factor (IGF)-I and IGF binding protein-1 in male adult rat offspring".

Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2012-10-31
6. Oxytocin treatment during early life influences reproductive performance in ad libitum fed and food-restricted female rats
Open this publication in new window or tab >>Oxytocin treatment during early life influences reproductive performance in ad libitum fed and food-restricted female rats
2002 (English)In: Biology of the Neonate, ISSN 0006-3126, E-ISSN 1421-9727, Vol. 81, no 2, 132-138 p.Article in journal (Refereed) Published
Abstract [en]

Oxytocin treatment may permanently alter endocrine axes resulting in anti-stress and anabolic effects. However, the nutritional status influences the effects of oxytocin. The specific aims of this study were to investigate the effects of postnatal oxytocin treatment on reproductive performance in adult life, by studying maternal weight gain, adiposity, plasma levels of IGF-I as well as fetal and placental weights in the following groups of animals: (1) Ad libitum fed dams coming from ad libitum fed mothers. (2) Ad libitum fed dams coming from food-restricted mothers. (3) Food-restricted dams coming from ad libitum fed mothers. (4) Food-restricted dams coming from food-restricted mothers. Oxytocin treatment postnatally had long-term effects and increased adiposity in pregnant dams and stimulated placental and fetal growth relative to saline-treated dams. However, if the dams themselves had been exposed to food restriction during fetal life, the effect of postnatal oxytocin treatment changed. The oxytocin-treated mothers were still fatter but had smaller fetuses. In conclusion, postnatal oxytocin treatment influences reproductive performance in later life but is dependent on the mother’s previous and current nutritional experience.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25310 (URN)10.1159/000047198 (DOI)9751 (Local ID)9751 (Archive number)9751 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-10-31

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