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Gene expression of inflammatory markers and growth factors in placenta in relation to maternal obesity and foetal and postnatal growth
Örebro University, School of Medical Sciences.
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Maternal obesity is a growing health problem, that contributes to obstetrical complications in pregnancy, as well as neonatal morbidity and mortality. The placenta serves for gas and nutrient exchange between the mother and the foetus, and obesity may influence and modify placental growth and function. The aims of this thesis were to investigate associations between maternal obesity without associated morbidity and gene expression of inflammatory markers and growth factors in the placenta, as well as offspring birth weight and postnatal growth. 

Study I and III were designed as matched case-control studies including 32 obese women with an early pregnancy body mass index (BMI) ≥ 35.0 kg/m2, study II was an experimental study examining twelve placentas of normal weight women, and study IV was a cohort study including 109 obese women with a BMI ≥ 34.5 kg/m2. In studies I-IV analyses of gene expression were performed and in study III additionally cord blood concentrations were determined. 

No difference was found in the occurrence of placental gene expression of inflammatory markers or growth factors between obese and normal weight women, nor did the sampling site in placentas of normal weight women influence gene expression of these markers, except for leptin gene (LEP) and insulin receptor gene (INSR) expression. Ghrelin gene (GHRL) and LEP expression, as well as cord blood ghrelin and adiponectin levels, was not altered in maternal obesity, and a negatively U-shaped relationship between LEP expression and infant birth weight (BW) z-scores was observed in the placentas of obese women.

In conclusion, no statistically significant difference in gene expressions of inflammatory markers and growth factors in the placenta between severely obese and normal weight women was found. These results are in contrast with earlier studies and could be due to the fact that we examined mainly healthy obese women. The correlations we found between gene expression of leptin in the placenta and the birth weight of the infants warrants further studies.

Place, publisher, year, edition, pages
Örebro: Örebro University , 2020. , p. 93
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 221
Keywords [en]
obesity, pregnancy, placenta, gene expression, cytokines
National Category
Other Basic Medicine
Identifiers
URN: urn:nbn:se:oru:diva-80923ISBN: 978-91-7529-354-7 (print)OAI: oai:DiVA.org:oru-80923DiVA, id: diva2:1420639
Public defence
2020-10-16, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2020-03-31 Created: 2020-03-31 Last updated: 2020-09-21Bibliographically approved
List of papers
1. Placental gene expression of inflammatory markers and growth factors: a case control study of obese and normal weight women
Open this publication in new window or tab >>Placental gene expression of inflammatory markers and growth factors: a case control study of obese and normal weight women
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2015 (English)In: Journal of Perinatal Medicine, ISSN 0300-5577, E-ISSN 1619-3997, Vol. 43, no 2, p. 159-164Article in journal (Refereed) Published
Abstract [en]

Objective: To survey the placental gene expression of inflammatory markers and growth factors in non-smoking obese women with an uncomplicated pregnancy without associated morbidity and delivery at term compared with normal weight women.

Methods: Placental tissue samples from 32 obese women (body mass index, BMI >= 35.0 kg/m(2)) were compared with samples from 94 normal weight women (BMI 18.5-25.0 kg/m(2)) matched for age (+/- 1 year), gestational age (+/- 3 days), parity and mode of delivery. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to analyse toll receptor-2 and -4, interleukin-6 and -8, tumour necrosis factor-alpha, leptin, adiponectin, insulin-like growth factor-1 and -2, hepatocyte growth factor, hepatocyte growth factor receptor and insulin receptor.

Results: There was no significant difference in gene expression in placental tissue samples from obese and normal weight women.

Conclusion: We found no difference in the occurrence of inflammatory marker and growth factor mRNA levels in placental tissue samples from a large group of obese women without associated morbidity and with healthy infants compared to a closely matched control group of healthy normal weight women. Compared with the previous studies, this anomalous finding may be explained by the absence of associated morbidity in the obese women in our study.

Place, publisher, year, edition, pages
Walter de Gruyter, 2015
Keywords
Obesity, pregnancy
National Category
Obstetrics, Gynecology and Reproductive Medicine Pediatrics
Research subject
Obstetrics and Gynaecology; Pediatrics
Identifiers
urn:nbn:se:oru:diva-44240 (URN)10.1515/jpm-2013-0343 (DOI)000350338000005 ()25014513 (PubMedID)2-s2.0-84945571575 (Scopus ID)
Note

Funding Agency:

Foundation for Medical Research, Orebro University Hospital

Available from: 2015-04-14 Created: 2015-04-14 Last updated: 2023-12-08Bibliographically approved
2. Expression of genes involved in inflammation and growth: does sampling site in human full-term placenta matter?
Open this publication in new window or tab >>Expression of genes involved in inflammation and growth: does sampling site in human full-term placenta matter?
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2019 (English)In: Journal of Perinatal Medicine, ISSN 0300-5577, E-ISSN 1619-3997, Vol. 47, no 5, p. 539-546Article in journal (Refereed) Published
Abstract [en]

Objective: To investigate the placental gene expression of substances in the inflammatory cascade and growth factors at nine different well-defined sampling sites in full-term placentas from 12 normal weight healthy non-smoking women with an uncomplicated singleton pregnancy.

Methods: All placentas (six girls and six boys) were delivered vaginally. Quantitative real-time polymerase chain reaction was used to analyze toll receptor-2 and -4, interleukin-6 and -8, tumor necrosis factor-α, leptin, ghrelin, insulin-like growth factor-1 and -2, hepatocyte growth factor, hepatocyte growth factor receptor and insulin receptor (IR).

Results: The leptin gene and the IR gene showed higher expression in lateral regions near the chorionic plate compared to central regions near the basal plate (P = 0.028 and P = 0.041, respectively).

Conclusion: Our results suggest that the sampling site may influence the gene expression for leptin and IR in placental tissue obtained from full-term normal pregnancies. We speculate that this may be due to differences in placental structure and perfusion and may be important when future studies are designed.

Place, publisher, year, edition, pages
Walter de Gruyter, 2019
Keywords
Cytokines, gene expression, growth factors, placenta, sampling
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:oru:diva-73427 (URN)10.1515/jpm-2018-0290 (DOI)000473532900008 ()30920955 (PubMedID)2-s2.0-85063721684 (Scopus ID)
Note

Funding Agencies:

Research Committee of Region Örebro County  

Nyckelfonden, Örebro University Hospital  

Available from: 2019-04-04 Created: 2019-04-04 Last updated: 2020-12-01Bibliographically approved
3. Placental ghrelin and leptin expression and cord blood ghrelin, adiponectin, leptin, and C-peptide levels in severe maternal obesity
Open this publication in new window or tab >>Placental ghrelin and leptin expression and cord blood ghrelin, adiponectin, leptin, and C-peptide levels in severe maternal obesity
2017 (English)In: The Journal of Maternal-Fetal & Neonatal Medicine, ISSN 1476-7058, E-ISSN 1476-4954, Vol. 31, no 21, p. 2839-2846Article in journal (Refereed) Published
Abstract [en]

PURPOSE: The purpose of this study is to investigate placental ghrelin and leptin expression as well as cord blood ghrelin and adiponectin levels in maternal obesity and associations between placental ghrelin expression, cord blood ghrelin levels and maternal and infant variables.

MATERIALS AND METHODS: Placental ghrelin and leptin expression were analyzed by RT-PCR in 32 severely obese and 32 matched normal-weight women. Cord blood ghrelin, adiponectin, leptin, and C-peptide concentrations were analyzed by ELISA.

RESULTS: Neither ghrelin nor leptin expression and neither cord blood ghrelin nor adiponectin levels differed between the groups. Placental ghrelin expression was associated with BMI at delivery in the obese women (r = 0.424, p = .016) and in the infants born to normal-weight women with their weight z-scores at six (r = -0.642, p = .010), nine (r = -0.441, p = .015), and 12 months of age (r = -0.402, p = .028).

CONCLUSIONS: Placental ghrelin and leptin expression as well as cord blood ghrelin and adiponectin levels do not seem to be altered in severe maternal obesity. Placenta-derived ghrelin may influence the infants' postnatal weight gain, but possibly only when the mother has normal weight.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2017
Keywords
Adiponectin, birth weight, ghrelin, leptin, obesity, placenta
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:oru:diva-61734 (URN)10.1080/14767058.2017.1358262 (DOI)000440610300007 ()28783996 (PubMedID)2-s2.0-85027047254 (Scopus ID)
Note

Funding agencies:

Research Committee of Region Örebro County

Nyckelfonden, Örebro University Hospital

Available from: 2017-11-06 Created: 2017-11-06 Last updated: 2020-12-01Bibliographically approved
4. Gene expression of leptin, leptin receptor isoforms, and inflammatory cytokines in placentas of obese women: associations to birth weight and foetal sex
Open this publication in new window or tab >>Gene expression of leptin, leptin receptor isoforms, and inflammatory cytokines in placentas of obese women: associations to birth weight and foetal sex
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(English)Manuscript (preprint) (Other academic)
National Category
Other Basic Medicine
Identifiers
urn:nbn:se:oru:diva-85819 (URN)
Available from: 2020-09-21 Created: 2020-09-21 Last updated: 2020-12-01Bibliographically approved

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