Metabolism of Progesterone by Preimplantation mouse Blastocysts in Culture1

Wu, Jia-Rung

doi:10.1095/biolreprod36.3.549

Cited by 15 publications

(8 citation statements)

References 28 publications

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“…There is evidence that rodent blastocysts synthesize P 4 or structurally similar steroids (47)(48)(49) and that gene expression differs in embryo-induced decidua and experimentally induced deciduoma (39). Since our previous results show that Fkbp52 and Pgr are expressed in blastocysts (12), it is possible that P 4 synthesized from blastocysts enhances PR/FKBP52 signaling locally at their sites of apposition in the uterus.…”

Section: Discussionmentioning

confidence: 71%

FKBP52 deficiency–conferred uterine progesterone resistance is genetic background and pregnancy stage specific

Tranguch¹,

Wang²,

Daikoku³

et al. 2007

J. Clin. Invest.

118

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Immunophilin FKBP52 serves as a cochaperone to govern normal progesterone (P 4 ) receptor (PR) function. Using Fkbp52 -/-mice, we show intriguing aspects of uterine P 4 /PR signaling during pregnancy. Implantation failure is the major phenotype found in these null females, which is conserved on both C57BL6/129 and CD1 backgrounds. However, P 4 supplementation rescued implantation and subsequent decidualization in CD1, but not C57BL6/129, null females. Surprisingly, experimentally induced decidualization in the absence of blastocysts failed in Fkbp52 -/-mice on either background even with P 4 supplementation, suggesting that embryonic signals complement uterine signaling for this event. Another interesting finding was that while P 4 at higher than normal pregnancy levels conferred PR signaling sufficient for implantation in CD1 null females, these levels were inefficient in maintaining pregnancy to full term. However, elevating P 4 levels further restored PR signaling to a level optimal for successful term pregnancy with normal litter size. Collectively, the results show that the indispensability of FKBP52 in uterine P 4 /PR signaling is a function of genetic disparity and is pregnancy stage specific. Since there is evidence for a correlation between P 4 supplementation and reduced risks of P 4 -resistant recurrent miscarriages and remission of endometriosis, these findings have clinical implications for genetically diverse populations of women.

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Section: Discussionmentioning

confidence: 71%

FKBP52 deficiency–conferred uterine progesterone resistance is genetic background and pregnancy stage specific

Tranguch¹,

Wang²,

Daikoku³

et al. 2007

J. Clin. Invest.

118

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“…Although only 2 of the 4 known progesterone metabolites were isolated and identified, there was no reason to believe that the other two should not be present in the medium as the culture conditions were similar to those reported earlier (Wu, 1987). Furthermore, in cultures containing embryos, the amount of radioactivity remaining at the origin after t.l.c.…”

Section: Discussionmentioning

confidence: 87%

“…It should be stressed that, in our hands, neither this solvent system nor Wiebe's complete two-dimensional solvent system (Wiebe, 1982) could adequately separate allopregnanolone from pregnenolone. An earlier study of progesterone metabolism by cultured Day-4 and -5 blasto¬ cysts (Wu, 1987) indicated that the appearance rate of allopregnanolone was about 3-5 times that of 3 5 in Day-5 blastocyst cultures and 1-5-4-5 times ofthat in Day-4 blastocyst cultures. The appearance rate of allopregnanolone in the present study was therefore very conservatively estimated (particularly during the second half of culture) to be twice that of 3 5 at all time periods.…”

Section: Methodsmentioning

confidence: 96%

“…The crystallization procedure (Wu, 1987) was repeated for as many times as the sample allowed (3-7 times). All the crystal samples were dried, weighed and dissolved in the scintillation cocktail Opti-Fluor (Packard Instrument Co, Downers Grove, IL, USA) for counting the radioactivity in a Packard Tri-Carb liquid scintillation analyser at an efficiency of 47%.…”

Section: Methodsmentioning

confidence: 99%

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Conversion of pregnenolone to progesterone by mouse morulae and blastocysts

Wu¹,

Liu²

1990

Reproduction

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When mouse morulae, early blastocysts and implanting blastocysts were cultured with tritiated pregnenolone, tritiated progesterone and its metabolites, 5 alpha-pregnan-3,20-dione and 3 alpha-hydroxy-5 alpha-pregnan-20-one, were isolated from the medium. It appears that mouse embryos can make progesterone from pregnenolone and the progesterone is quickly metabolized into various metabolites. These abilities increase with development. It is suggested that the mouse embryo can make progesterone and may regulate its own progesterone level for optimal development.

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“…Preimplantation mouse blastocysts in culture can easily metabolize progesterone [32]. Considering that parthenogenetic activation induced by progesterone required long exposure in the range of hours, progesterone may exert its eff e c t s a f t e r b e i n g m e t a b o l i z e d .…”

Section: Discussionmentioning

confidence: 99%