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Differential triiodothyronine responsiveness and transport by human cytotrophoblasts from normal and growth-restricted pregnancies.

Vasilopoulou E, Loubière LS, Martín-Santos A, McCabe CJ, Franklyn JA, Kilby MD, Chan SY - J. Clin. Endocrinol. Metab. (2010)

Bottom Line: Abnormal placentation in human pregnancy is associated with intrauterine fetal growth restriction (IUGR).The secretion of human chorionic gonadotropin was significantly increased by IUGR cytotrophoblasts compared with normal cytotrophoblasts (P < 0.001), independently of T(3) treatment.IUGR cytotrophoblasts demonstrate altered responsiveness to T(3) with significant effects on cell survival and apoptosis compared with normal cytotrophoblasts.

View Article: PubMed Central - PubMed

Affiliation: School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.

ABSTRACT

Context: Abnormal placentation in human pregnancy is associated with intrauterine fetal growth restriction (IUGR). Our group has previously reported the association between severe IUGR, lower fetal circulating concentrations of thyroid hormones (THs), and altered expression of TH receptors and TH transporters within human placental villi. We postulate that altered TH bioavailability to trophoblasts may contribute to the pathogenesis of IUGR.

Design and objective: Cytotrophoblasts were isolated from normal and IUGR human placentae to compare their responsiveness to T(3) and their capability for T(3) transport.

Results: Compared with normal cytotrophoblasts, the viability of IUGR cytotrophoblasts (assessed by methyltetrazoleum assay) was significantly reduced (P < 0.001), whereas apoptosis (assessed using caspase 3/7 activity and M30 immunoreactivity) was significantly increased after T(3) treatment for 48 h (P < 0.001 and P < 0.01, respectively). The secretion of human chorionic gonadotropin was significantly increased by IUGR cytotrophoblasts compared with normal cytotrophoblasts (P < 0.001), independently of T(3) treatment. Net transport of [(125)I]T(3) was 20% higher by IUGR cytotrophoblasts compared with normal cytotrophoblasts (P < 0.001), and this was accompanied by a 2-fold increase in the protein expression of the TH transporter, monocarboxylate transporter 8, as assessed by Western immunoblotting (P < 0.01).

Conclusions: IUGR cytotrophoblasts demonstrate altered responsiveness to T(3) with significant effects on cell survival and apoptosis compared with normal cytotrophoblasts. Increased monocarboxylate transporter 8 expression and intracellular T(3) accumulation may contribute to the altered T(3) responsiveness of IUGR cytotrophoblasts.

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Effect of T3 on hCG secretion by normal and IUGR cytotrophoblasts. The hCG secretion at 48 h after T3 treatment (normal, n = 9; IUGR, n = 6) and 72 h after T3 treatment (normal, n = 8; IUGR, n = 6) was assessed and normalized to the hCG secretion at 0 h of T3 treatment (18 h after culture), which was given an arbitrary value of 100%. **, P < 0.01; ***, P < 0.001.
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Figure 3: Effect of T3 on hCG secretion by normal and IUGR cytotrophoblasts. The hCG secretion at 48 h after T3 treatment (normal, n = 9; IUGR, n = 6) and 72 h after T3 treatment (normal, n = 8; IUGR, n = 6) was assessed and normalized to the hCG secretion at 0 h of T3 treatment (18 h after culture), which was given an arbitrary value of 100%. **, P < 0.01; ***, P < 0.001.

Mentions: Overall, the rise in hCG secretion over time was higher in IUGR compared with normal cytotrophoblasts (P < 0.001; Fig. 3). Post hoc tests demonstrated that this effect was significant in both the absence (P < 0.001) and the presence (P < 0.01) of T3.


Differential triiodothyronine responsiveness and transport by human cytotrophoblasts from normal and growth-restricted pregnancies.

Vasilopoulou E, Loubière LS, Martín-Santos A, McCabe CJ, Franklyn JA, Kilby MD, Chan SY - J. Clin. Endocrinol. Metab. (2010)

Effect of T3 on hCG secretion by normal and IUGR cytotrophoblasts. The hCG secretion at 48 h after T3 treatment (normal, n = 9; IUGR, n = 6) and 72 h after T3 treatment (normal, n = 8; IUGR, n = 6) was assessed and normalized to the hCG secretion at 0 h of T3 treatment (18 h after culture), which was given an arbitrary value of 100%. **, P < 0.01; ***, P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3050105&req=5

Figure 3: Effect of T3 on hCG secretion by normal and IUGR cytotrophoblasts. The hCG secretion at 48 h after T3 treatment (normal, n = 9; IUGR, n = 6) and 72 h after T3 treatment (normal, n = 8; IUGR, n = 6) was assessed and normalized to the hCG secretion at 0 h of T3 treatment (18 h after culture), which was given an arbitrary value of 100%. **, P < 0.01; ***, P < 0.001.
Mentions: Overall, the rise in hCG secretion over time was higher in IUGR compared with normal cytotrophoblasts (P < 0.001; Fig. 3). Post hoc tests demonstrated that this effect was significant in both the absence (P < 0.001) and the presence (P < 0.01) of T3.

Bottom Line: Abnormal placentation in human pregnancy is associated with intrauterine fetal growth restriction (IUGR).The secretion of human chorionic gonadotropin was significantly increased by IUGR cytotrophoblasts compared with normal cytotrophoblasts (P < 0.001), independently of T(3) treatment.IUGR cytotrophoblasts demonstrate altered responsiveness to T(3) with significant effects on cell survival and apoptosis compared with normal cytotrophoblasts.

View Article: PubMed Central - PubMed

Affiliation: School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.

ABSTRACT

Context: Abnormal placentation in human pregnancy is associated with intrauterine fetal growth restriction (IUGR). Our group has previously reported the association between severe IUGR, lower fetal circulating concentrations of thyroid hormones (THs), and altered expression of TH receptors and TH transporters within human placental villi. We postulate that altered TH bioavailability to trophoblasts may contribute to the pathogenesis of IUGR.

Design and objective: Cytotrophoblasts were isolated from normal and IUGR human placentae to compare their responsiveness to T(3) and their capability for T(3) transport.

Results: Compared with normal cytotrophoblasts, the viability of IUGR cytotrophoblasts (assessed by methyltetrazoleum assay) was significantly reduced (P < 0.001), whereas apoptosis (assessed using caspase 3/7 activity and M30 immunoreactivity) was significantly increased after T(3) treatment for 48 h (P < 0.001 and P < 0.01, respectively). The secretion of human chorionic gonadotropin was significantly increased by IUGR cytotrophoblasts compared with normal cytotrophoblasts (P < 0.001), independently of T(3) treatment. Net transport of [(125)I]T(3) was 20% higher by IUGR cytotrophoblasts compared with normal cytotrophoblasts (P < 0.001), and this was accompanied by a 2-fold increase in the protein expression of the TH transporter, monocarboxylate transporter 8, as assessed by Western immunoblotting (P < 0.01).

Conclusions: IUGR cytotrophoblasts demonstrate altered responsiveness to T(3) with significant effects on cell survival and apoptosis compared with normal cytotrophoblasts. Increased monocarboxylate transporter 8 expression and intracellular T(3) accumulation may contribute to the altered T(3) responsiveness of IUGR cytotrophoblasts.

Show MeSH
Related in: MedlinePlus