Endocrine Abstracts (2011) 25 OC5.8

Altered fetoplacental growth in monocarboxylate transporter 8 (Mct8) knockout mice

Elisavet Vasilopoulou1, Heike Heuer2, Marija Trajkovic2, Laurence Loubière1, Christopher McCabe1, Jayne Franklyn1, Mark Kilby1 & Shiao Chan1

1University of Birmingham, Birmingham, UK; 2Leibniz Institute for Age Research-Fritz Lipmann Institute, Jena, Germany.

The plasma membrane thyroid hormone (TH) transporter, MCT8, is present in the human placenta from early gestation and is postulated to participate in transplacental transfer of TH. In vitro, MCT8 overexpression decreases the survival of human cytotrophoblast in a TH-independent manner.

Objective: To examine the role of Mct8 in fetoplacental growth using the Mct8 knockout (ko) mouse model.

Methods: Heterozygous females were mated with male ko mice. Male wild-type (wt) and ko fetoplacental tissues were obtained from two litters before (E14.5) and after (E18.5) the onset of fetal TH production. Mct8 protein was localized in the mouse placenta by immunohistochemistry. The volume fractions of the labyrinthine (Lz) and junctional (Jz) zones of the placenta were estimated using stereology. Cyclin D1 (proliferation) and Caspase 3 (apoptosis) protein expression was assessed by western immunoblotting.

Results: At both E14.5 and E18.5, Mct8 protein was expressed in decidua, in spongiotrophoblast and glycogen cells in the Jz, in cytotrophoblast and syncytiotrophoblast cells in the Lz, in the wall of chorionic blood vessels and in the chorionic membrane. At E18.5, male ko fetuses were lighter (1273±24.5 mg) than male wt (1397±28.6 mg; P<0.05), whilst their placentae were heavier (ko: 90.3±6.5 mg; wt: 77.3±2.8 mg; P<0.05). This was accompanied by increased Cyclin D1 and decreased Caspase 3 protein expression in ko compared with wt placentae. Fetoplacental weight ratios were decreased (30%; P<0.01) in ko compared with wt fetuses. The volume fraction of the Lz was reduced by 10% (P<0.05) in ko compared with wt placentae with no difference in the absolute volume of Lz.

Conclusions: The ubiquitous localization of Mct8 in mouse placenta is similar to that observed in humans. Its localisation in trophoblasts within the Lz, suggests a role for Mct8 in transplacental transport. Furthermore, lack of Mct8 results in reduced placental efficiency with a compensatory increase in placental size.

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