A Progesterone Antagonist Cannot Prevent Fetal Survival if the Uterine Horn is Incised.

Tamada, Hiromichi; Inaba, Toshio; Sawada, Tsutomu

doi:10.1507/endocrj.45.785

Cited by 3 publications

(3 citation statements)

References 22 publications

(17 reference statements)

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“…Since treatment with E 2 restored the changes in uterine physical properties caused by the Fad treatment and prevented fetal injuries, it is possible that the specific role of estrogen during the second half of pregnancy is to develop the uterine tissue framework needed to maintain normal fetal growth in rats. The importance of the uterine physical environment to fetal survival during late pregnancy has been demonstrated in ovariectomized rats and rats treated with a progesterone antagonist (Tamada & Mori 1995, Tamada et al 1998. Although high doses of androgens have estrogenic effects and maintain successful pregnancy in the ovariectomized progesterone-treated rats (Hosoda et al 1984), increased production of androgen in the Fad-treated rats could not have overcome the influences of the estrogen deficiency.…”

Section: Discussionmentioning

confidence: 99%

The effects of the aromatase inhibitor fadrozole hydrochloride on fetuses and uteri in late pregnant rats

Tamada¹,

Shimizu²,

Inaba³

et al. 2004

Journal of Endocrinology

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It is well known that progesterone and estrogen are essential hormones for maintaining pregnancy in most mammals. Some specific roles of progesterone for the maintenance of pregnancy have been clarified, but the role of estrogen is not well known. This study examines the effects of the aromatase inhibitor, fadrozole hydrochloride (Fad), on fetuses, uterine physical properties and the mRNA expression of the uterine enzymes that are related to collagen metabolism during late pregnancy in rats. Continuous s.c. infusion with 300 µg/day Fad from day 14 of pregnancy (day 1=the day of sperm detection) reduced the concentration of plasma estradiol-17 (E 2 ), and did not change that of plasma progesterone, compared with controls. The treatment increased the intrauterine pressure and reduced the size and compliance of the uterine tissue framework. It also caused injuries (hematomata on the extremities) in about one-quarter of fetuses by day 20. The collagen content of the uterine ampullae was not changed by the treatment. Uterine mRNA expressions of matrix metalloproteinase-1 (MMP-1), which degrades collagens, and of lysyl oxidase (LO), which is necessary for the formation of intra-and inter-molecular cross-links of collagen, were examined by quantitative RT-PCR. The treatment with Fad had no effect on the expression of MMP-1 mRNA and increased that of LO mRNA. Daily s.c. injection with 0·2 µg E 2 restored the changes in uterine physical properties and the mRNA expression of LO caused by the Fad treatment, and prevented fetal injury, indicating that the influences of Fad treatment are due to estrogen deficiency but not to toxicological effects of Fad. These results imply that estrogen deficiency during late pregnancy in rats obstructs development of the uterine tissue framework so as to cause fetal injury. It is possible that an increase in the uterine expression of LO gene may be involved in this obstruction.

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Section: Discussionmentioning

confidence: 99%

The effects of the aromatase inhibitor fadrozole hydrochloride on fetuses and uteri in late pregnant rats

Tamada¹,

Shimizu²,

Inaba³

et al. 2004

Journal of Endocrinology

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“…The E 1 S concentration in the blood of the smaller littermate group was significantly higher than those in the other groups, as was the birth and placental weight. Tamada et al . (1998) reported that ovariectomy increased placental weight in the incised uterine horn of pregnant rats.…”

Section: Discussionmentioning

confidence: 99%

Relationships among steroid hormone levels in newborn piglets, birth weight, placental weight, vitality of offspring and litter size

Ohtaki

Moriyoshi²,

Nakada

et al. 2012

Animal Science Journal

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Blood estrone sulfate (E(1) S), estrone (E(1) ), estradiol (E(2) ) and progesterone (P(4) ) in newborn piglets were measured to clarify the relationships among birth and placental weight, vitality of offspring and litter size. First, the association between vital status (normal, weak and stillborn) from 165 newborn piglets of 18 litters and steroid concentrations; second, steroid concentrations from 152 newborn normal piglets and litter size; and third, steroid content in fetal placenta from 50 newborn normal piglets of six litters and litter size, were investigated. In the normal group, the birth and placental weight were significantly higher than those in the other groups. Blood E(1) S levels in the stillborn group were significantly lower, whereas E(1) , E(2) and P(4) were significantly higher compared to the normal group. Blood and placental E(1) S levels in the small litter group were significantly higher than those in the other groups. However, there was no significant difference among the three litter size groups in the levels of steroid hormones in maternal blood. These results indicate that vitality of newborn piglets is related to E(1) S concentration of neonate, to birth weight and placental weight. However, steroid hormone concentrations of newborn piglets were greatly affected by the number of littermates.

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“…ovariectomy and/or treatment with anti-P RU 486 in late pregnant rats, indicating that indispensable actions of ovarian hormones for fetal survival are directed to the physical properties of uteri in late pregnancy [10,11]. Namely, well-known action of P for inhibition of uterine smooth muscle activity through its receptor signaling [12] and enlargement of uterine tissue framework for rapidly growing fetuses by P plus estrogen could be critical for maintenance of late pregnancy.…”

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confidence: 99%

Rescue of the fetal damage associated with high intrauterine pressure by 17β-estradiol injection in ovariectomized progesterone-treated pregnant mice

2018

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The present study examined the effects of progesterone (P) and 17β-estradiol (E2) on fetal damage and intrauterine pressure in ovariectomized pregnant mice. The mice were ovariectomized on gestational day (GD) 9 (copulation plug = GD 0), and daily subcutaneous injection of various doses of P (2, 3 or 4 mg) or 4 mg P plus E2 (0.05 or 0.1 μg) was given thereafter. Although P alone increased percentage of normal fetuses on GD 17 dose-dependently, fetal injury with edematous hematomata on their extremities was frequently observed. In the group treated with 4 mg P, the injured fetus was found at the highest percentage (18%) and intrauterine pressure was significantly higher than that in intact pregnant mice (controls). No injured fetus on GD 17 was found by the treatment with 4 mg P plus 0.05 or 0.1 μg E2, and the treatments decreased the intrauterine pressure to the level of controls. Percentage of normal fetuses in the ovariectomized mice treated with 4 mg P plus 0.05 μg E2 was similar to that of controls, while that in the ovariectomized mice treated with 4 mg P plus 0.1 μg E2 markedly decreased. The results suggest that estrogen decreases intrauterine pressure to defend fetal damage in ovariectomized P-treated mice, and a high estrogen level interrupted pregnancy while keeping this estrogen action.

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A Progesterone Antagonist Cannot Prevent Fetal Survival if the Uterine Horn is Incised.

Cited by 3 publications

References 22 publications

The effects of the aromatase inhibitor fadrozole hydrochloride on fetuses and uteri in late pregnant rats

The effects of the aromatase inhibitor fadrozole hydrochloride on fetuses and uteri in late pregnant rats

Relationships among steroid hormone levels in newborn piglets, birth weight, placental weight, vitality of offspring and litter size

Rescue of the fetal damage associated with high intrauterine pressure by 17β-estradiol injection in ovariectomized progesterone-treated pregnant mice

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