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Maternal obesity is associated with a reduction in placental taurine transporter activity.

Ditchfield AM, Desforges M, Mills TA, Glazier JD, Wareing M, Mynett K, Sibley CP, Greenwood SL - Int J Obes (Lond) (2014)

Bottom Line: These pregnancy complications are associated with dysfunctional syncytiotrophoblast, the transporting epithelium of the human placenta.Placental TauT activity was significantly lower in obese women (BMI⩾30) than women of ideal weight (P<0.03) and inversely related to maternal BMI (19-49 kg m(-)(2); P<0.05; n=61).Long-term exposure (48 h) of placental villous explants to leptin or IL-6 did not affect TauT activity.

View Article: PubMed Central - PubMed

Affiliation: 1] Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester, UK [2] Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

ABSTRACT

Background/objectives: Maternal obesity increases the risk of poor pregnancy outcome including stillbirth, pre-eclampsia, fetal growth restriction and fetal overgrowth. These pregnancy complications are associated with dysfunctional syncytiotrophoblast, the transporting epithelium of the human placenta. Taurine, a β-amino acid with antioxidant and cytoprotective properties, has a role in syncytiotrophoblast development and function and is required for fetal growth and organ development. Taurine is conditionally essential in pregnancy and fetal tissues depend on uptake of taurine from maternal blood. We tested the hypothesis that taurine uptake into placental syncytiotrophoblast by the taurine transporter protein (TauT) is lower in obese women (body mass index (BMI)⩾30 kg m(-)(2)) than in women of ideal weight (BMI 18.5-24.9 kg m(-)(2)) and explored potential regulatory factors.

Subjects/methods: Placentas were collected from term (37-42-week gestation), uncomplicated, singleton pregnancies from women with BMI 19-49 kg m(-)(2). TauT activity was measured as the Na(+)-dependent uptake of (3)H-taurine into placental villous fragments. TauT expression in membrane-enriched placental samples was investigated by western blot. In vitro studies using placental villous explants examined whether leptin or IL-6, adipokines/cytokines that are elevated in maternal obesity, regulates TauT activity.

Results: Placental TauT activity was significantly lower in obese women (BMI⩾30) than women of ideal weight (P<0.03) and inversely related to maternal BMI (19-49 kg m(-)(2); P<0.05; n=61). There was no difference in TauT expression between placentas of ideal weight and obese class III (BMI⩾40) subjects. Long-term exposure (48 h) of placental villous explants to leptin or IL-6 did not affect TauT activity.

Conclusions: Placental TauT activity at term is negatively related to maternal BMI. We propose that the reduction in placental TauT activity in maternal obesity could lower syncytiotrophoblast taurine concentration, compromise placental development and function, and reduce the driving force for taurine efflux to the fetus, thereby increasing the risk of poor pregnancy outcome.

No MeSH data available.


Related in: MedlinePlus

(a) TauT activity at day 7 of culture is higher in placental villous explants maintined in medium with no added taurine (▴) compared with that with 100 μm added taurine (●). (a) Representative culture (least squares linear regression). (b) TauT activity in explants at day 7 of culture in medium with 100 μm added taurine (●) was not significantly different from activity determined in freshly isolated tissue fragments from the same placenta (○) (mean±s.e.; n=3 placentas; least squares linear regression). (c) Time course of hCG secretion by untreated placental villous explants over 7 days of culture (mean±s.e.; n=5) indicated endocrine viability. (d) TauT activity (90 min) in explants at day 7 of culture, expressed as a percentage of the controls (100% dotted line), was unaffected by 48 h exposure to either leptin or IL-6 (Wilcoxon signed rank test vs control (100%): median and interquartile range; n=5).
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fig4: (a) TauT activity at day 7 of culture is higher in placental villous explants maintined in medium with no added taurine (▴) compared with that with 100 μm added taurine (●). (a) Representative culture (least squares linear regression). (b) TauT activity in explants at day 7 of culture in medium with 100 μm added taurine (●) was not significantly different from activity determined in freshly isolated tissue fragments from the same placenta (○) (mean±s.e.; n=3 placentas; least squares linear regression). (c) Time course of hCG secretion by untreated placental villous explants over 7 days of culture (mean±s.e.; n=5) indicated endocrine viability. (d) TauT activity (90 min) in explants at day 7 of culture, expressed as a percentage of the controls (100% dotted line), was unaffected by 48 h exposure to either leptin or IL-6 (Wilcoxon signed rank test vs control (100%): median and interquartile range; n=5).

Mentions: Figure 4a shows an example of TauT activity in explants cultured in standard medium (10–25 μm taurine contributed by serum) and medium with 100 μm taurine to simulate maternal plasma taurine concentration. As previously reported,46, 43 TauT activity was upregulated following culture in low-taurine conditions. Figure 3b shows that there was no difference in TauT activity after 7 days of explant culture in medium containing 100 μm taurine and activity in freshly isolated villi from the same placenta. This confirms that the addition of 100 μm taurine in culture restores TauT activity to normal. Subsequent experiments to assess effects of leptin and IL-6 were carried out using the explants cultured in medium with 100 μm taurine.


Maternal obesity is associated with a reduction in placental taurine transporter activity.

Ditchfield AM, Desforges M, Mills TA, Glazier JD, Wareing M, Mynett K, Sibley CP, Greenwood SL - Int J Obes (Lond) (2014)

(a) TauT activity at day 7 of culture is higher in placental villous explants maintined in medium with no added taurine (▴) compared with that with 100 μm added taurine (●). (a) Representative culture (least squares linear regression). (b) TauT activity in explants at day 7 of culture in medium with 100 μm added taurine (●) was not significantly different from activity determined in freshly isolated tissue fragments from the same placenta (○) (mean±s.e.; n=3 placentas; least squares linear regression). (c) Time course of hCG secretion by untreated placental villous explants over 7 days of culture (mean±s.e.; n=5) indicated endocrine viability. (d) TauT activity (90 min) in explants at day 7 of culture, expressed as a percentage of the controls (100% dotted line), was unaffected by 48 h exposure to either leptin or IL-6 (Wilcoxon signed rank test vs control (100%): median and interquartile range; n=5).
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig4: (a) TauT activity at day 7 of culture is higher in placental villous explants maintined in medium with no added taurine (▴) compared with that with 100 μm added taurine (●). (a) Representative culture (least squares linear regression). (b) TauT activity in explants at day 7 of culture in medium with 100 μm added taurine (●) was not significantly different from activity determined in freshly isolated tissue fragments from the same placenta (○) (mean±s.e.; n=3 placentas; least squares linear regression). (c) Time course of hCG secretion by untreated placental villous explants over 7 days of culture (mean±s.e.; n=5) indicated endocrine viability. (d) TauT activity (90 min) in explants at day 7 of culture, expressed as a percentage of the controls (100% dotted line), was unaffected by 48 h exposure to either leptin or IL-6 (Wilcoxon signed rank test vs control (100%): median and interquartile range; n=5).
Mentions: Figure 4a shows an example of TauT activity in explants cultured in standard medium (10–25 μm taurine contributed by serum) and medium with 100 μm taurine to simulate maternal plasma taurine concentration. As previously reported,46, 43 TauT activity was upregulated following culture in low-taurine conditions. Figure 3b shows that there was no difference in TauT activity after 7 days of explant culture in medium containing 100 μm taurine and activity in freshly isolated villi from the same placenta. This confirms that the addition of 100 μm taurine in culture restores TauT activity to normal. Subsequent experiments to assess effects of leptin and IL-6 were carried out using the explants cultured in medium with 100 μm taurine.

Bottom Line: These pregnancy complications are associated with dysfunctional syncytiotrophoblast, the transporting epithelium of the human placenta.Placental TauT activity was significantly lower in obese women (BMI⩾30) than women of ideal weight (P<0.03) and inversely related to maternal BMI (19-49 kg m(-)(2); P<0.05; n=61).Long-term exposure (48 h) of placental villous explants to leptin or IL-6 did not affect TauT activity.

View Article: PubMed Central - PubMed

Affiliation: 1] Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester, UK [2] Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

ABSTRACT

Background/objectives: Maternal obesity increases the risk of poor pregnancy outcome including stillbirth, pre-eclampsia, fetal growth restriction and fetal overgrowth. These pregnancy complications are associated with dysfunctional syncytiotrophoblast, the transporting epithelium of the human placenta. Taurine, a β-amino acid with antioxidant and cytoprotective properties, has a role in syncytiotrophoblast development and function and is required for fetal growth and organ development. Taurine is conditionally essential in pregnancy and fetal tissues depend on uptake of taurine from maternal blood. We tested the hypothesis that taurine uptake into placental syncytiotrophoblast by the taurine transporter protein (TauT) is lower in obese women (body mass index (BMI)⩾30 kg m(-)(2)) than in women of ideal weight (BMI 18.5-24.9 kg m(-)(2)) and explored potential regulatory factors.

Subjects/methods: Placentas were collected from term (37-42-week gestation), uncomplicated, singleton pregnancies from women with BMI 19-49 kg m(-)(2). TauT activity was measured as the Na(+)-dependent uptake of (3)H-taurine into placental villous fragments. TauT expression in membrane-enriched placental samples was investigated by western blot. In vitro studies using placental villous explants examined whether leptin or IL-6, adipokines/cytokines that are elevated in maternal obesity, regulates TauT activity.

Results: Placental TauT activity was significantly lower in obese women (BMI⩾30) than women of ideal weight (P<0.03) and inversely related to maternal BMI (19-49 kg m(-)(2); P<0.05; n=61). There was no difference in TauT expression between placentas of ideal weight and obese class III (BMI⩾40) subjects. Long-term exposure (48 h) of placental villous explants to leptin or IL-6 did not affect TauT activity.

Conclusions: Placental TauT activity at term is negatively related to maternal BMI. We propose that the reduction in placental TauT activity in maternal obesity could lower syncytiotrophoblast taurine concentration, compromise placental development and function, and reduce the driving force for taurine efflux to the fetus, thereby increasing the risk of poor pregnancy outcome.

No MeSH data available.


Related in: MedlinePlus