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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

Representative western blots of placental membrane-enriched fractions from three women of ideal weight (IW) and three women who were obese class III (BMI⩾40 kg m−2: obese, OB) subjects probed for TauT and β-actin. Protein loading was 50 μg per lane. (a) After probing for TauT, an immunoreactive species was detected at ~69 kDa in all samples. (b) After re-probing membranes for β-actin, an immunoreactive species was detected at ~44 kDa. (c) Scatter plots display densitometric analysis of TauT signal intensity after normalizing to β-actin (line at median). There was no significant difference in TauT protein expression between IW (n=6) and OB (n=7) groups (Mann–Whitney U-test: P>0.05). (d) Placental TauT activity, in the same placentas in which TauT expression was determined, was significantly lower in class III obese women (n=7; (○)) than women of IW (n=6; (○)) (mean±s.e.; *P<0.05, least squares linear regression).
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fig3: Representative western blots of placental membrane-enriched fractions from three women of ideal weight (IW) and three women who were obese class III (BMI⩾40 kg m−2: obese, OB) subjects probed for TauT and β-actin. Protein loading was 50 μg per lane. (a) After probing for TauT, an immunoreactive species was detected at ~69 kDa in all samples. (b) After re-probing membranes for β-actin, an immunoreactive species was detected at ~44 kDa. (c) Scatter plots display densitometric analysis of TauT signal intensity after normalizing to β-actin (line at median). There was no significant difference in TauT protein expression between IW (n=6) and OB (n=7) groups (Mann–Whitney U-test: P>0.05). (d) Placental TauT activity, in the same placentas in which TauT expression was determined, was significantly lower in class III obese women (n=7; (○)) than women of IW (n=6; (○)) (mean±s.e.; *P<0.05, least squares linear regression).

Mentions: Figure 3a shows representative western blots of TauT expression in membrane-enriched placental samples from ideal weight (n=6) and obese class III (n=7) subjects in which TauT activity was significantly reduced (Figure 3d). After probing with anti-TauT antibody, an immunoreactive signal for TauT was detected at ~69 kDa (Figure 3a), corresponding to the molecular mass of the protein encoded by the predominant TauT transcript in the placenta.45 To confirm protein integrity and correct for protein loading, membranes were probed for β-actin and an immunoreactive species was detected at ~44 kDa (Figure 3b). Densitometry of TauT expression normalized to β-actin revealed that there was no difference in TauT expression in placentas of ideal weight and obese class III subjects (Figure 3c).


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)

Representative western blots of placental membrane-enriched fractions from three women of ideal weight (IW) and three women who were obese class III (BMI⩾40 kg m−2: obese, OB) subjects probed for TauT and β-actin. Protein loading was 50 μg per lane. (a) After probing for TauT, an immunoreactive species was detected at ~69 kDa in all samples. (b) After re-probing membranes for β-actin, an immunoreactive species was detected at ~44 kDa. (c) Scatter plots display densitometric analysis of TauT signal intensity after normalizing to β-actin (line at median). There was no significant difference in TauT protein expression between IW (n=6) and OB (n=7) groups (Mann–Whitney U-test: P>0.05). (d) Placental TauT activity, in the same placentas in which TauT expression was determined, was significantly lower in class III obese women (n=7; (○)) than women of IW (n=6; (○)) (mean±s.e.; *P<0.05, least squares linear regression).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4389721&req=5

fig3: Representative western blots of placental membrane-enriched fractions from three women of ideal weight (IW) and three women who were obese class III (BMI⩾40 kg m−2: obese, OB) subjects probed for TauT and β-actin. Protein loading was 50 μg per lane. (a) After probing for TauT, an immunoreactive species was detected at ~69 kDa in all samples. (b) After re-probing membranes for β-actin, an immunoreactive species was detected at ~44 kDa. (c) Scatter plots display densitometric analysis of TauT signal intensity after normalizing to β-actin (line at median). There was no significant difference in TauT protein expression between IW (n=6) and OB (n=7) groups (Mann–Whitney U-test: P>0.05). (d) Placental TauT activity, in the same placentas in which TauT expression was determined, was significantly lower in class III obese women (n=7; (○)) than women of IW (n=6; (○)) (mean±s.e.; *P<0.05, least squares linear regression).
Mentions: Figure 3a shows representative western blots of TauT expression in membrane-enriched placental samples from ideal weight (n=6) and obese class III (n=7) subjects in which TauT activity was significantly reduced (Figure 3d). After probing with anti-TauT antibody, an immunoreactive signal for TauT was detected at ~69 kDa (Figure 3a), corresponding to the molecular mass of the protein encoded by the predominant TauT transcript in the placenta.45 To confirm protein integrity and correct for protein loading, membranes were probed for β-actin and an immunoreactive species was detected at ~44 kDa (Figure 3b). Densitometry of TauT expression normalized to β-actin revealed that there was no difference in TauT expression in placentas of ideal weight and obese class III subjects (Figure 3c).

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