トロホブラストの生物学

抄録

The trophoblast of human placenta is composed of syncytiotrophoblast (S-cell) and cytotrophoblast (C-cell). C-cell displays proliferative properties, while S-cell displays little potential for proliferation. A close similarity between cytologic localization of myc product and [₃H] thymidine labeling suggests that myc expression is linked to trophoblast proliferation. In situ hybridization with cDNA probes revealed that mRNA expression of hCG α and hCG β are initiated before syncytial formation, whereas hPL mRNA is expressed only in fully differentiated S-cell. EGF and EGF receptor (EGF-R) in 4-5 weeks placenta were localized to C-cell, whereas EGF and EGF-R in 6-12 weeks placenta were localized to S-cell. Consistent with these findings, EGF exerted gestational age dependent dual action on early placenta: one was to stimulate trophoblast proliferation in 4-5 weeks placenta and the other was to stimulate differentiated trophoblast function in 6-12 weeks placenta. An optimal dose of thyroid hormone stimulated progesterone, estradiol, hCG and hPL production in early placental tissues. Furthermore, women with unfavorable outcome of threatened abortion had lower T₄, T₃, free T₄ and free T₃ levels, as compared to women with favorable outcome. These data imply a role for thyroid hormone in maintaining early pregnancy. On the other hand, progesterone selectively inhibited hCG(α, β) mRNAs expression and decreased hCG secretion in normal placental tissues, whereas choriocarcinoma did not respond to progesterone. This suggests that inhibitory regulation of hCG synthesis in choriocarcinoma is different from normal palcenta. Characterization of choriocarcinoma hCG revealed that there are striking differences in carbohydrate structures between normal hCG and choriocarcinoma hCG. Sialic acid content in choriocarcinoma hCG was extremely lower compared to that in normal hCG. The biochemical detection of the alteration in hCG sugar chains is useful for early diagnosis of choriocarcinoma.