Investigation of HoxB3 and Growth Factors Expression in Placentas of Various Gestational Ages

Abstract

An evaluation of transforming growth factor beta (TGFβ), hepatocyte growth factor (HGF), basic fibroblast growth factor (FGF-2), fibroblast growth factors receptor 1 (FGFR1) and Hox-positive cells in the human placenta, and their correlation with gestational time at delivery and pregnancy outcomes, may provide not only a better understanding of the role of Hox genes and growth factors in human development, but also may be of clinical importance in reproductive medicine. This study analyzed the immunohistochemical identification of TGFβ, HGF, FGF-2, FGFR1 and HoxB3 in placentas of various gestational ages. We found few (+) TGFβ, moderate (++) FGF-2 and numerous (+++) HGF and FGFR1 positive structures. Occasional (0/+) to numerous (+++) HoxB3-positive structures were detected in different types of placental cells specifically, cytotrophoblasts, syncytiotrophoblast, extravillous trophoblasts, and Höfbauer cells. Correlating the appearance of HoxB3 staining in placentas with neonatal parameters, we found a statistically significant negative correlation with ponderal index (r = -0.323, p = 0.018) and positive correlation with neonate body length (r = 0.541, p = 0.046). The number of HoxB3-positive cells did not correlate with growth factors and gestational age, but with neonatal anthropometrical parameters, indicating the role of HoxB3 not only in placental development, but also in the longitudinal growth of the fetus. TGFβ and FGF-2 did not play a significant role in the development of the placenta beyond 22nd week of pregnancy, while HGF and FGFR1 immunoreactive cells increased with advancing gestation, indicating increasingly evolving maturation (growth, proliferation) of the placenta, especially in the third trimester.

Keywords: development; fetus; gene; growth; immunocytochemistry; intrauterine growth; microscopy; placenta.

Figure 1

HoxB3-containing structures of the placenta. (a) Maternal part and tertiary villi of a 31 gestational week placenta with numerous (+++) HoxB3-containing cells of extravillous trophoblast, cytotrophoblast and syncytiotrophoblast (HoxB3 IMH, X 250). (b) Maternal part of a 32 gestational week placenta with numerous (+++) HoxB3-containing Höfbauer cells (HoxB3 IMH, X 250). (c) Maternal part of a 40 gestational week placenta with numerous (+++) HoxB3-containing extravillous trophoblast and Höfbauer cells (HoxB3 IMH, X 250).

Figure 2

Immunoreactive structures of placenta. (a) Moderate amount (++) of TGFβ positive cells in a full-term placenta (TGFβ IMH, X250). (b) Moderate amount (++) of TGFβ positive cells in a preterm placenta (TGFβ IMH, X250). (c) Abundance (++++) of HGF positive cells in a full-term placenta (HGF IMH, X 250). (d) Abundance (++++) of HGF positive cells in a preterm placenta (HGF IMH, X 250). (e) Moderate amount (++) of FGF-2 positive cells in a full-term placenta (FGF-2 IMH, X 250). (f) Moderate amount (++) of FGF-2 positive cells in a preterm placenta (FGF-2 IMH, X 250). (g) Moderate to numerous (++/+++) FGFR1 positive cells in a full-term placenta (FGFR1 IMH, X 250). (h) Numerous (+++) FGFR1 positive cells in a preterm placenta (FGFR1 IMH, X 250).