妊娠・分娩と胎児-胎盤系

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I. Theoretical basis of measurement of estriol during pregnancy 1) It was clarified that the feto (adrenal and liver)-placental unit plays an important role in the biosynthesis of estriol during pregnancy. The theoretical basis of the usefulness of estriol estimation in maternal urine as the indicator of fetal viability is therefore established, and a simplified estriol assay (LAIR-3 minites method) was developped. 2) As to the steroid values in the amniotic fluid during pregnancy, high level of progesterone (P_4) in the first trimester and prominent rises of DHA-S and estriol values near term were shown. Furthermore, transferance of amniotic DHA-S to the mother through the amniotic membrane was demonstrated by the in vivo study using deuterium labeled DHA-S given in the amniotic fluid. 3) In vivo study using deuterated pregnenolone sulfate (P_5-S) given in the maternal circulation demonstrated that maternal P_5-S was partially used as the precursor of placental P_4. Therefore, it is suggested that the precursor of placental P_4 is mainly derived from the feto-placental side rather than the maternal one. II. Changes of steroidal environement near term 1) Steroid hormone assay by gas chromatography mass-spectrometry using deuterium labeled compound as internal standard was developped, and (fetal adrenal) steroid values in maternal blood were measured. DHA-S, 16α-OH- DHA-S and estriol values increase in the prepain and labor period and P_4 and 20α-OH-P_4 values decrease during labor. 2) In vivo study using deuterium labeled DHA-S given to the fetal side in the perinal period demonstrated that DHA-S originated from fetal adrenal transferred to the mother through placenta without being subjected to the aromatisation. 3) The elevation of uterine sensitivity to oxytocin in the perinal period is closely related to both the increases of DHA-S and estriol levels, and the decrease of P_4 values in the maternal blood. 4) As to the hormonal factors of hypothalamo-posteriol pituitary system, the levels of estrogen stimulated neurophysin (ESN) and oxytocin in the maternal blood elevated parallel with the increase of estrogen level in the prepain period. 5) The administration of DHA-S (100mg, twice a week) in the perinatal period accelerate the maturation of uterine cervix with con-comitant augumentation of DHA-S concentration and increased prolin hydroxylase activity in the cervical tissue. The patients who received DHA-S terminate pregnancy ca 5 days earlier than those received placevo. Shortening of the duration of labor in DHA-S received patients was also observed by double blind test. These data may indicate that the augumentation of DHA-S level in prelabor period plays an important role in the initiation of parturition. III. Hypothesis of the mechanism on initiation of parturition in human 1) From the findings mentioned above, hypothesis model on the onset of delivery in human was proposed in relation between the maturation patterns of 3 factors of delivery and profiles of feto-placental steroids values in the perinal period. 2) The dramatic increase of DHA-S in the maternal blood, main steroid originated from the fetal zone of fetal adrenal, could be the hormonal trigger of delivery in human. Following the dramatic increase of DHA-S in maternal blood and the changes of steroid metabolic functions of the placenta, placental estrogen transformed from DHA-S lead to increase ENS and oxytocin levels in the maternal blood, which in turn, initiate parturition. Furthermore, DHA-S accelerate both the maturation and softening of uterine cervix, and stimulate prostaglandin production in the amniotic 'membrane, which results in the myometrial contraction and then the termination of pregnancy.
社団法人日本産科婦人科学会の論文
1986-08-01

妊娠・分娩と胎児-胎盤系

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