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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) Uptake of 3H-taurine into villous fragments in the presence (●) and absence (○) of Na+ over 30–120 min in the placentas of ideal weight women. The Na+-dependent component of uptake (▴) indicates 3H-taurine uptake owing to TauT activity. There was a linear relationship between TauT activity and time over 30–120 min (least squares linear regression: r2=0.56, P<0.0001). (b) Placental TauT activity was significantly lower in obese women (BMI⩾30 kg m−2; n=27 (○)) compared with women of ideal weight (BMI 18.5–24.9 kg m−2; n=22 (●)) (mean±s.e.; *P<0.03 least squares linear regression). (c) Placental TauT activity (120 min) according to the BMI category (mean±s.e.; *P<0.05; Kruskall–Wallis with Dunn's multiple comparison post hoc test). (d) Placental TauT activity (120 min) was inversely related to maternal BMI (least squares linear regression: r2=0.098; P<0.014 n=61).
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fig2: (a) Uptake of 3H-taurine into villous fragments in the presence (●) and absence (○) of Na+ over 30–120 min in the placentas of ideal weight women. The Na+-dependent component of uptake (▴) indicates 3H-taurine uptake owing to TauT activity. There was a linear relationship between TauT activity and time over 30–120 min (least squares linear regression: r2=0.56, P<0.0001). (b) Placental TauT activity was significantly lower in obese women (BMI⩾30 kg m−2; n=27 (○)) compared with women of ideal weight (BMI 18.5–24.9 kg m−2; n=22 (●)) (mean±s.e.; *P<0.03 least squares linear regression). (c) Placental TauT activity (120 min) according to the BMI category (mean±s.e.; *P<0.05; Kruskall–Wallis with Dunn's multiple comparison post hoc test). (d) Placental TauT activity (120 min) was inversely related to maternal BMI (least squares linear regression: r2=0.098; P<0.014 n=61).

Mentions: The uptake of 3H-taurine into villous fragments is shown in Figure 2a using placentas from women of ideal weight as an example. TauT activity, the Na+-dependent component of 3H-taurine uptake, was linear up to 120 min for all categories of BMI indicating that activity was measured at initial rate (data not shown). TauT activity (30–120 min) was significantly lower in placentas of obese (BMI⩾30) as compared with ideal weight women (Figure 2b; 21% lower at 120 min). As TauT activity was linear up to 120 min, this time point was selected for subsequent analyses. To explore the relationship between BMI category and TauT activity, subjects with a BMI ⩾30 were divided into their obesity subgroups (Figure 2c). There was no difference in TauT activity in women who were overweight compared with women of ideal weight. There was a reduction in TauT activity in obesity and this was significantly lower in placentas of obese class III women (BMI⩾40) compared with women of ideal weight. When TauT activity was related to maternal BMI as a continuous variable, a significant negative relationship was observed over the BMI range 19–49 (Figure 2d).


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) Uptake of 3H-taurine into villous fragments in the presence (●) and absence (○) of Na+ over 30–120 min in the placentas of ideal weight women. The Na+-dependent component of uptake (▴) indicates 3H-taurine uptake owing to TauT activity. There was a linear relationship between TauT activity and time over 30–120 min (least squares linear regression: r2=0.56, P<0.0001). (b) Placental TauT activity was significantly lower in obese women (BMI⩾30 kg m−2; n=27 (○)) compared with women of ideal weight (BMI 18.5–24.9 kg m−2; n=22 (●)) (mean±s.e.; *P<0.03 least squares linear regression). (c) Placental TauT activity (120 min) according to the BMI category (mean±s.e.; *P<0.05; Kruskall–Wallis with Dunn's multiple comparison post hoc test). (d) Placental TauT activity (120 min) was inversely related to maternal BMI (least squares linear regression: r2=0.098; P<0.014 n=61).
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fig2: (a) Uptake of 3H-taurine into villous fragments in the presence (●) and absence (○) of Na+ over 30–120 min in the placentas of ideal weight women. The Na+-dependent component of uptake (▴) indicates 3H-taurine uptake owing to TauT activity. There was a linear relationship between TauT activity and time over 30–120 min (least squares linear regression: r2=0.56, P<0.0001). (b) Placental TauT activity was significantly lower in obese women (BMI⩾30 kg m−2; n=27 (○)) compared with women of ideal weight (BMI 18.5–24.9 kg m−2; n=22 (●)) (mean±s.e.; *P<0.03 least squares linear regression). (c) Placental TauT activity (120 min) according to the BMI category (mean±s.e.; *P<0.05; Kruskall–Wallis with Dunn's multiple comparison post hoc test). (d) Placental TauT activity (120 min) was inversely related to maternal BMI (least squares linear regression: r2=0.098; P<0.014 n=61).
Mentions: The uptake of 3H-taurine into villous fragments is shown in Figure 2a using placentas from women of ideal weight as an example. TauT activity, the Na+-dependent component of 3H-taurine uptake, was linear up to 120 min for all categories of BMI indicating that activity was measured at initial rate (data not shown). TauT activity (30–120 min) was significantly lower in placentas of obese (BMI⩾30) as compared with ideal weight women (Figure 2b; 21% lower at 120 min). As TauT activity was linear up to 120 min, this time point was selected for subsequent analyses. To explore the relationship between BMI category and TauT activity, subjects with a BMI ⩾30 were divided into their obesity subgroups (Figure 2c). There was no difference in TauT activity in women who were overweight compared with women of ideal weight. There was a reduction in TauT activity in obesity and this was significantly lower in placentas of obese class III women (BMI⩾40) compared with women of ideal weight. When TauT activity was related to maternal BMI as a continuous variable, a significant negative relationship was observed over the BMI range 19–49 (Figure 2d).

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