Effect of the Fetal THRB Genotype on the Placenta
F Salas-Lucia, MN Stan, H James… - The Journal of …, 2023 - academic.oup.com
F Salas-Lucia, MN Stan, H James, A Rajwani, XH Liao, AM Dumitrescu, S Refetoff
The Journal of Clinical Endocrinology & Metabolism, 2023•academic.oup.comContext Pregnant women with mutations in the thyroid hormone receptor beta (THRB) gene
expose their fetuses to high thyroid hormone (TH) levels shown to be detrimental to a normal
fetus (NlFe) but not to an affected fetus (AfFe). However, no information is available about
differences in placental TH regulators. Objective To investigate whether there are
differences in placentas associated with a NlFe compared with an AfFe, we had the unique
opportunity to study placentas from 2 pregnancies of the same woman with THRB mutation …
expose their fetuses to high thyroid hormone (TH) levels shown to be detrimental to a normal
fetus (NlFe) but not to an affected fetus (AfFe). However, no information is available about
differences in placental TH regulators. Objective To investigate whether there are
differences in placentas associated with a NlFe compared with an AfFe, we had the unique
opportunity to study placentas from 2 pregnancies of the same woman with THRB mutation …
Context
Pregnant women with mutations in the thyroid hormone receptor beta (THRB) gene expose their fetuses to high thyroid hormone (TH) levels shown to be detrimental to a normal fetus (NlFe) but not to an affected fetus (AfFe). However, no information is available about differences in placental TH regulators.
Objective
To investigate whether there are differences in placentas associated with a NlFe compared with an AfFe, we had the unique opportunity to study placentas from 2 pregnancies of the same woman with THRB mutation G307D. One placenta supported a NlFe while the other an AfFe.
Methods
Sections of placentas were collected and frozen at −80 °C after term delivery of a NlFe and an AfFe. Two placentas from healthy women of similar gestational age were also obtained. The fetal origin of the placental tissues was established by gDNA quantitation of genes on the X and Y chromosomes and THRB gene. Expression and enzymatic activity of deiodinases 2 and 3 were measured. Expression of following genes was also quantitated: MCT10, MCT8, LAT1, LAT2, THRB, THRA.
Results
The placenta carrying the AfFe exhibited a significant reduction of deiodinase 2 and 3 activities as well as the expression of the TH transporters MCT10, LAT1 and LAT2, and THRA.
Conclusion
We present the first study of the effect of the fetal THRB genotype on the placenta. Though limited by virtue of the rarity of THRB mutations and sample availability, we show that the fetal THRB genotype influences the levels of TH regulators in the placenta.
Oxford University Press