[Trophoblast: its functional regulation and pathophysiological profiles].
The trophoblast of the human placenta is composed of two layers: syncytiotrophoblast and cytotrophoblast. Cytotrophoblast displays highly proliferative and invasive properties, while syncytiotrophoblast displays little potential for proliferation. Regulatory factors involved in processes of proliferation and differentiation of the trophoblast still remain to be elucidated. Immunohistologically, myc product was predominantly localized to cytotrophoblastic cells. A close similarity between cytologic localization of myc product and tritiated thymidine labeling of placental explant suggests that myc protein expression is linked to trophoblast proliferation. A similar pattern of cytological localization was observed with the use of anti-PDGF antibody, supporting a possibility that PDGF also plays a role in the trophoblast proliferation. Human trophoblast produces two major proteins, hCG and hPL. hCG stimulates progesterone production by corpus luteum. hPL exerts lipolytic action which assures glucose supply to the fetus. In situ hybridization with cDNA probes for hCG(alpha, beta) and hPL revealed that mRNA expression of hCG alpha and probably hCG beta are initiated before syncytial formation, whereas hPL mRNA is expressed only in fully differentiated syncytiotrophoblast. hCG levels in maternal serum are the highest in early pregnancy and thereafter decline, while hCG alpha and hPL levels increase throughout pregnancy. In patients with choriocarcinoma, serum hPL levels are extremely low despite high levels of hCG. In this context, hCG beta mRNA levels remarkably declined in term placenta compared to early placenta, and hPL mRNA was little observed in choriocarcinoma. EGF and EGF receptor (EGF-R) in 4-5 weeks placenta were almost exclusively localized to cytotrophoblasts, whereas EGF and EGF-R in 6-12 weeks placenta were predominantly localized to syncytiotrophoblasts. In the second and third trimester placentas, EGF was mainly localized to cytotrophoblasts, while EGF-R was predominantly localized to syncytiotrophoblasts. It is of great interest that the cytologic localization of EGF and EGF-R in human placenta varies according to the age of gestation. The fact that mitotically active cytotrophoblasts in 4-5 weeks placenta were positive for both EGF and EGF-R expression suggests that EGF and EGF-R may be involved in the control of multiplication of cytotrophoblasts very early in the first trimester. On the other hand, the fact that mitotically inactive syncytiotrophoblasts in 6-12 weeks placenta were positive for both EGF and EGF-R expression suggests that EGF and EGF-R may play a role in the induction of differentiated function of trophoblast in 6-12 weeks gestation. In fact, EGF stimulated hCG and hPL production and secretion by cultured early placental tissues.(ABSTRACT TRUNCATED AT 400 WORDS)
Mochizuki
M
M
Department of Obstetrics and Gynecology, Kobe University School of Medicine.
D014408:Biomarkers, Tumor / Q000032:analysis; D002454:Cell Differentiation; D002455:Cell Division; D006063:Chorionic Gonadotropin / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D018997:Chorionic Gonadotropin, beta Subunit, Human; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000502:physiology; D004815:Epidermal Growth Factor / Q000502:physiology; D005260:Female; D016259:Genes, myc; D005833:Genital Neoplasms, Female / Q000175:diagnosis; D006801:Humans; D010446:Peptide Fragments / Q000032:analysis; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
D014408:Biomarkers, Tumor; D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D010446:Peptide Fragments; C063554:urinary gonadotropin fragment; D004815:Epidermal Growth Factor; D003346:Corticotropin-Releasing Hormone