hepatocyte growth factor and placental development

1
1946 Letters June 1996 AmJ ObstetOynecol We all wish to avoid preventable cases of fetal-neonatal morbidity. However, there are many examples in obstet- rics of seemingly logical and enthusiastically adopted therapies that ultimately proved to be ineffective, costly, and morbid. Cesarean delivery for autoimmune throm- bocytopenia may be one of them. Robert M. Silver, MD, D. Ware Branch, MD, and James R. Scott, MD Department of Obstetricsand Gynecology, University of Utah School of Medicine, Room 2B200, 50 N. MedicalDr., Salt Lake City, UT 84132 REFERENCES 1. Christiaens GCML, Helmerhorst FM. Validity of intrapartum diagnosis of fetal thrombocytopenia. Am J Obstet Gynecol 1987;157:864-5. 2. Bussel JB, Christiaens G. Birth platelet counts in sequential newborns of mothers with ITP: do the platelet counts change with subsequent babies? (abstract). Blood 1993;82(suppl. 1): 202a. 3. Yamada H, Fujimoto S. Perinatal management of idiopathic thrombocytopenic purpura in pregnancy: risk factors for pas- sive immune thrombocytopenia. Ann Hemato11994;68:39-42. 4. Moise KJ, Cotton DB. Discordant fetal platelet counts in a twin gestation complicated by idiopathic thrombocytopenic purpura. Am J Obstet Gynecol 1987;156:1141-2. 6/8/73586 Hepatocyte growth factor and placental development To th~Editors: Hepatocyte growth factor (HGF) is a pleio- tropic growth factor now known to be a multifunctional cytokine that regulates cell growth, motility, and morpho- genesis) The human placenta is composed of a variety of different cell types. The growth, development, and orien- tation of such placental epithelial, mesenchymal, and endothelial cell types would require intricate control. The further potential importance of HGF in placental development has been indicated by recent "knockout" studies in mice with homologous recombination to one parental gene encoding HGF, the progeny of which dem- onstrated both intrauterine growth restriction and abnor- mal placental development.2 The recent article by Horibe et al. (Horibe N, Oka- moto T, Itakura A, Nakanishi T, Suzuki T, Kazeto S, et al. Levels of hepatocyte growth factor in maternal serum and amniotic fluid. Am J Obstet Gynecol 1995;173:937-41) indicates HGF in the amniotic fluid of human pregnan- cies with a level that was demonstrated to be maximal in the second trimester. Further in vitro evidence indicated that HGF was released from cultured amniocytes into the experimental supernatant which was maximal in tissues cultured from second-trimester placentas. We have recently demonstrated the distribution of messenger ribonucleic acid for both HGF and its recep- tor, c-met, in human term placenta by in situ hybridiza- tion? The HGF messenger ribonucleic acid was strongly evident in the perivascular stromal cells surrounding the villous vasculature and the amniochorionic membranes. A relatively weak and diffuse hybridization signal for c-met messenger ribonucleic acid was present throughout the villous trophoblast, most pronounced in the vasculosyn- cytial membrane but also in the amnion and chorion. These results indicate that the amniochorionic mem- branes are an important site of HGF synthesis in the term placenta and offer a possible explanation for the pres- ence of HGF in the amniotic fluid described by Horibe et al. Mark Kilby, MD, and Martin Whittle, MD Division of Fetal Medicine, Department of Obstetricsand Gynaecology, University of Birmingham, Birmingham, United Kingdom B15 2TG Alastair Strain, PhD Department of Biochemistry, University of Birmingham, Birmingham, United Kingdom B15 2TG REFERENCES 1. Strain AJ, Ismail T, Arakaki N, Hishida T, Kitamura Y, Daiku- hara Y, et al. Native and recombinant human hepatocyte growth factors are highly potent promoters of DNA synthesis in both human and rat hepatocytes. J Clin Invest 1991;87: 1853-7. 2. Uehara Y, Minowa O, Mori C, Shiota K, KunoJ, Noda T, et al. Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor. Nature 1995;373: 702-5. 3. Kilby M, Afford S, Li X, Strain A, Ahmed A, Whitde M. Localization of hepatocyte growth factor and its receptor (c-met) protein and mRNA in human term placenta. Growth Factors. 1996;13:1-7. 6/8/73587 Reply To the Editors: We thank Kilby et al. for their interest in our work and their contribution to the study of hepatocyte growth factor implications in fetal development. As was demonstrated by "knockout" studies in mice, hepatocyte growth factor seems to play a pivotal role in villous formation during placental development. On the other hand, it is highly probable that hepatocyte growth factor has many other functions for the fetus, in that its concentration is extremely high in the second trimester. In that regard, studies are in progress in our laboratory to better understand its role in alveolar formation in the fetus. T. Okamoto, MD, and A. Itakura, MD Department of Obstetricsand Gynecology,Nagoya University School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, 466,Japan 6/8/73588

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1946 Letters June 1996 AmJ Obstet Oynecol

We all wish to avoid preventable cases of fetal-neonatal morbidity. However, there are many examples in obstet- rics of seemingly logical and enthusiastically adopted therapies that ultimately proved to be ineffective, costly, and morbid. Cesarean delivery for autoimmune throm- bocytopenia may be one of them.

Robert M. Silver, MD, D. Ware Branch, MD, and James R. Scott, MD

Department of Obstetrics and Gynecology, University of Utah School of Medicine, Room 2B200, 50 N. Medical Dr., Salt Lake City, UT 84132

REFERENCES 1. Christiaens GCML, Helmerhorst FM. Validity of intrapartum

diagnosis of fetal thrombocytopenia. Am J Obstet Gynecol 1987;157:864-5.

2. Bussel JB, Christiaens G. Birth platelet counts in sequential newborns of mothers with ITP: do the platelet counts change with subsequent babies? (abstract). Blood 1993;82(suppl. 1): 202a.

3. Yamada H, Fujimoto S. Perinatal management of idiopathic thrombocytopenic purpura in pregnancy: risk factors for pas- sive immune thrombocytopenia. Ann Hemato11994;68:39-42.

4. Moise KJ, Cotton DB. Discordant fetal platelet counts in a twin gestation complicated by idiopathic thrombocytopenic purpura. Am J Obstet Gynecol 1987;156:1141-2.

6/8/73586

Hepatocyte growth factor and placental development To th~Editors: Hepatocyte growth factor (HGF) is a pleio- tropic growth factor now known to be a multifunctional cytokine that regulates cell growth, motility, and morpho- genesis) The human placenta is composed of a variety of different cell types. The growth, development, and orien- tation of such placental epithelial, mesenchymal, and endothelial cell types would require intricate control. The further potential importance of HGF in placental development has been indicated by recent "knockout" studies in mice with homologous recombination to one parental gene encoding HGF, the progeny of which dem- onstrated both intrauterine growth restriction and abnor- mal placental development. 2

The recent article by Horibe et al. (Horibe N, Oka- moto T, Itakura A, Nakanishi T, Suzuki T, Kazeto S, et al. Levels of hepatocyte growth factor in maternal serum and amniotic fluid. Am J Obstet Gynecol 1995;173:937-41) indicates HGF in the amniotic fluid of human pregnan- cies with a level that was demonstrated to be maximal in the second trimester. Further in vitro evidence indicated that HGF was released from cultured amniocytes into the experimental supernatant which was maximal in tissues cultured from second-trimester placentas.

We have recently demonstrated the distribution of messenger ribonucleic acid for both HGF and its recep-

tor, c-met, in human term placenta by in situ hybridiza- t ion? The HGF messenger ribonucleic acid was strongly evident in the perivascular stromal cells surrounding the villous vasculature and the amniochorionic membranes. A relatively weak and diffuse hybridization signal for c-met messenger ribonucleic acid was present throughout the villous trophoblast, most pronounced in the vasculosyn- cytial membrane but also in the amnion and chorion. These results indicate that the amniochorionic mem- branes are an important site of HGF synthesis in the term placenta and offer a possible explanation for the pres- ence of HGF in the amniotic fluid described by Horibe et al.

Mark Kilby, MD, and Martin Whittle, MD

Division of Fetal Medicine, Department of Obstetrics and Gynaecology, University of Birmingham, Birmingham, United Kingdom B15 2TG

Alastair Strain, PhD

Department of Biochemistry, University of Birmingham, Birmingham, United Kingdom B15 2TG

REFERENCES 1. Strain AJ, Ismail T, Arakaki N, Hishida T, Kitamura Y, Daiku-

hara Y, et al. Native and recombinant human hepatocyte growth factors are highly potent promoters of DNA synthesis in both human and rat hepatocytes. J Clin Invest 1991;87: 1853-7.

2. Uehara Y, Minowa O, Mori C, Shiota K, KunoJ, Noda T, et al. Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor. Nature 1995;373: 702-5.

3. Kilby M, Afford S, Li X, Strain A, Ahmed A, Whitde M. Localization of hepatocyte growth factor and its receptor (c-met) protein and mRNA in human term placenta. Growth Factors. 1996;13:1-7.

6/8/73587

Reply To the Editors: We thank Kilby et al. for their interest in our work and their contribution to the study of hepatocyte growth factor implications in fetal development.

As was demonstrated by "knockout" studies in mice, hepatocyte growth factor seems to play a pivotal role in villous formation during placental development. On the other hand, it is highly probable that hepatocyte growth factor has many other functions for the fetus, in that its concentration is extremely high in the second trimester. In that regard, studies are in progress in our laboratory to better understand its role in alveolar formation in the fetus.

T. Okamoto, MD, and A. Itakura, MD Department of Obstetrics and Gynecology, Nagoya University School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, 466, Japan

6/8/73588