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Oxidative Stress, Angiogenesis and Inflammation in Normal Pregnancy and Postpartum
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aims were to investigate oxidative stress (I), angiogenesis (II) and inflammation (III-IV) in healthy women during pregnancy and postpartum. Oxidative stress was estimated by measurement of 8-iso-PGF and the antioxidants α- and γ-tocopherol. The angiogenic factors PlGF, VEGF-A and the antiangiogenic factor sFlt1 were measured to estimate angiogenesis. PTX3, IL-6, TNF-α and a PGF metabolite were measured to estimate inflammation.

Out of 52 included women, 15 had minor pregnancy complications and 37 were classified as normal. In study III data from all 52 women were used. For the other studies (I, II and IV) only data from the 37 women with normal pregnancy were used. Pregnancy was associated with increased levels of 8-iso-PGF with advancing gestational age. The median postpartum value corresponded to values observed in early gestation and a significant decrease was observed from late pregnancy to postpartum. Lipid-adjusted α- and γ-tocopherol levels decreased with advancing gestational age (I). PlGF increased from early pregnancy until weeks 29–30 and thereafter decreased until week 40. sFlt1 levels were relatively constant until weeks 29–30, when they increased, reaching a peak at weeks 39–40. Postpartum levels were low. The sFlt1:PlGF ratio decreased from weeks 9–12, was constantly low from weeks 19–20 to 37–38 and then increased to weeks 39–40. VEGF-A was detectable in only 8 % of the samples during pregnancy and in 64 % postpartum (II). There was a continuous increase of PTX3 as pregnancy progressed. The increase was most evident after week 31 with the highest levels just before delivery (III). IL-6 increased throughout pregnancy and remained high postpartum. No change in TNF-α could be seen with advancing gestational age or postpartum. The PGF metabolite levels increased throughout pregnancy and decreased postpartum (IV).

In conclusion, normal pregnancy is associated with mild oxidative stress and inflammation. This might have physiological effects for normal pregnancy development. By delineating how these mediators of oxidative stress, angiogenesis and inflammation fluctuate throughout normal pregnancy and postpartum, we have established a reference for studies of these factors in pregnancy complications.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. , 63 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 753
Keyword [en]
Angiogenesis, inflammation, IL-6, F2-isoprostanes, oxidative stress, Pentraxin 3, PGF2α, PlGF, pregnancy, sFlt1, TNF-α, VEGF-A
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology; Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-171165ISBN: 978-91-554-8314-2 (print)OAI: oai:DiVA.org:uu-171165DiVA: diva2:510315
Public defence
2012-05-04, Brömssalen, entrance 11, Gävle Sjukhus, Gävle, 13:15 (Swedish)
Opponent
Supervisors
Available from: 2012-04-23 Created: 2012-03-15 Last updated: 2012-08-01Bibliographically approved
List of papers
1. F(2)-isoprostanes, tocopherols and normal pregnancy
Open this publication in new window or tab >>F(2)-isoprostanes, tocopherols and normal pregnancy
2009 (English)In: Free radical research, ISSN 1071-5762, Vol. 43, no 6, 546-552 p.Article in journal (Refereed) Published
Abstract [en]

This study investigates oxidative stress and antioxidants in normal human pregnancy and post-partum period. Thirty-seven healthy women with normal pregnancies were included. Both urinary and serum samples were collected throughout the pregnancy and post-partum period. Oxidative stress was estimated by measuring the reliable in vivo marker, namely 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha,) an F(2)-isoprostane) and antioxidant status was evaluated by measuring alpha- and gamma-tocopherol in serum samples. Pregnancy was associated with successively increased levels of 8-iso-PGF(2alpha) with advancing gestational age. The median post-partum value corresponded to the values observed in early gestation and a significant decrease was observed from late pregnancy to the post-partum period. Lipid-adjusted alpha- and gamma-tocopherol levels decreased with advancing gestational age. This longitudinal study suggests that mild oxidative stress is involved in normal human pregnancy.

Keyword
Pregnancy, free radicals, oxidative stress, antioxidants, isoprostanes, human
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-106311 (URN)10.1080/10715760902902737 (DOI)000266979100004 ()19384749 (PubMedID)
Available from: 2009-06-18 Created: 2009-06-18 Last updated: 2012-04-23Bibliographically approved
2. A longitudinal study of plasma levels of soluble fms-like tyrosine kinase 1 (sFlt1), placental growth factor (PlGF), sFlt1: PlGF ratio and vascular endothelial growth factor (VEGF-A) in normal pregnancy
Open this publication in new window or tab >>A longitudinal study of plasma levels of soluble fms-like tyrosine kinase 1 (sFlt1), placental growth factor (PlGF), sFlt1: PlGF ratio and vascular endothelial growth factor (VEGF-A) in normal pregnancy
Show others...
2011 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 90, no 11, 1244-1251 p.Article in journal (Refereed) Published
Abstract [en]

Objective: To describe plasma levels of angiogenic (PlGF, VEGF-A) and anti-angiogenic (sFlt1) factors as well as the sFlt1:PlGF ratio throughout normal pregnancy and postpartum.

Design: Longitudinal prospective study.

Setting: One outpatient antenatal clinic in Uppsala, Sweden.

Population: Thirty-seven healthy women with normal pregnancies and normal neonatal outcome were included.

Methods: Blood samples were collected from each woman at least six times. Plasma levels of sFlt1, PlGF and VEGF-A were measured using commercially available ELISA kits. Main outcome measures. Median plasma levels, the 25th to the 75th percentile and the average change per gestational week of sFlt1, PlGF and the sFlt1:PlGF ratio.

Results: sFlt1 levels were relatively constant until weeks 29-30, when they increased, reaching a peak at week 40. An increase of 643pg/ml per week was observed from weeks 30 to 40. Postpartum levels were low. PlGF increased by 16pg/ml per week from early pregnancy until weeks 29-30 and thereafter decreased by 14pg/ml per week until week 40. The sFlt1:PlGF ratio decreased from weeks 9-12, was constantly low from weeks 19-20 to 37-38 and then increased to weeks 39-40. VEGF-A was detectable in only 8% of the samples during pregnancy and in 64% postpartum.

Conclusion: This longitudinal study demonstrates how sFlt1, PlGF and the sFlt1:PlGF ratio fluctuate throughout normal pregnancy and postpartum and may serve as a reference against which these factors can be studied in complicated pregnancies. VEGF-A levels were more often detectable postpartum.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-159606 (URN)10.1111/j.1600-0412.2011.01186.x (DOI)000296489700010 ()21568945 (PubMedID)
Available from: 2011-10-04 Created: 2011-10-04 Last updated: 2017-12-08Bibliographically approved
3. Pentraxin 3 Values During Normal Pregnancy
Open this publication in new window or tab >>Pentraxin 3 Values During Normal Pregnancy
2011 (English)In: Inflammation, ISSN 0360-3997, E-ISSN 1573-2576, Vol. 34, no 5, 448-451 p.Article in journal (Refereed) Published
Abstract [en]

Pentraxin 3 (PTX3) is an inflammatory molecule that has been reported to be a promising early biomarker for subsequent preeclampsia. The levels of PTX3 vary during pregnancy and it is thus a need to establish reference intervals during normal pregnancy. Repeated blood samples were collected from 52 healthy pregnant females. The samples were divided according to collection time into the following groups: week 7-17, week 17-24, week 24-28, week 28-31, week 31-34, week 34-38, before delivery and after delivery. The samples were analyzed for PTX3 with a sandwich ELISA and the 2.5 and 97.5 percentiles for each sample period was calculated. There was a continuous increase of serum PTX3 as pregnancy progressed. The increase was most evident after week 31 with the highest levels just before delivery.

National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-132552 (URN)10.1007/s10753-010-9252-x (DOI)000294820200018 ()20852923 (PubMedID)
Available from: 2010-10-21 Created: 2010-10-21 Last updated: 2017-12-12Bibliographically approved
4. Involvement of inflammation in normal pregnancy
Open this publication in new window or tab >>Involvement of inflammation in normal pregnancy
Show others...
2013 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 92, no 5, 601-605 p.Article in journal (Refereed) Published
Abstract [en]

Objective.

To study the role of inflammatory biomarkers of cytokine and cyclooxygenase origin throughout normal pregnancy and postpartum.

Design.

Longitudinal prospective study.

Setting.

One outpatient antenatal clinic in Uppsala, Sweden.

Population.

Thirty-seven healthy women with normal pregnancies and normal neonatal outcome were included. 

Methods.

Blood and urine samples were collected from each woman at least 6 times during pregnancy and postpartum. Plasma levels of IL-6 and TNF-α were measured by using ELISA kits and urine levels of PGF2α metabolite were measured by using RIA.

Main outcome measures.

Median plasma and urine levels, the 25:th to the 75:th percentile and the average change per gestational week of IL-6, TNF-α and PGF2α metabolite .

Results.

IL-6 levels increased significantly throughout pregnancy and postpartum levels remained high. No change in TNF-α could be seen with advancing gestational age or postpartum period. The PGF2α metabolite levels increased significantly throughout pregnancy and decreased in postpartum period.

Conclusion.

These results suggest that mild but significant inflammatory activity is involved in development of normal pregnancy and might have important physiological effects.

Keyword
IL-6, Inflammation, Pregnancy, TNF-α and PGF2α
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-171156 (URN)10.1111/aogs.12093 (DOI)000319060200016 ()23506129 (PubMedID)
Available from: 2012-03-15 Created: 2012-03-15 Last updated: 2017-12-07Bibliographically approved

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