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389 records · Page 22Linked to original sources

Emergency contraception alters progesterone-associated endometrial protein in serum and uterine luminal fluid.

OBJECTIVE: To evaluate the effect of high-dose oral contraceptives on serum and uterine luminal fluid progesterone-associated endometrial protein in the luteal phase. METHODS: Five ovulatory women participated in the study. In a control cycle, serum and uterine lavage samples were collected on luteal day 11. In the next cycle, on luteal day 9, the participants were given two 50-micrograms ethinyl estradiol-norgestrel tablets, repeated 12 hours later. Serum and uterine lavage samples were collected 48 hours (luteal day 11) after the last dose and analyzed by two-dimensional polyacrylamide gel electrophoresis and radioimmunoassays of the serum. RESULTS: Progesterone-associated endometrial protein levels were lower in sera from treated compared with control cycles. Analysis of serum levels of this protein by two-dimensional polyacrylamide gel electrophoresis did not reveal bands corresponding to the known size and charge characteristics (27 kd and pI of 4.9) in either control or treatment samples. On the other hand, in uterine lavage samples, a complete suppression of the 27-kd, pI-4.9 species was evident after treatment. CONCLUSION: High-dose ethinyl estradiol-norgestrel emergency contraception effectively suppresses progesterone-associated endometrial protein in the midluteal uterus, potentially altering the endometrial environment unfavorably and affecting the survival of the early embryo.

Contraceptives, Oral, Hormonal↗

Characterization of the normal progesterone and placental protein 14 responses to human chorionic gonadotropin stimulation in the luteal phase.

OBJECTIVE: To examine whether midluteal phase administration of the luteotrophic hormone hCG can result in higher and more stable serum levels than random sampling of P and placental protein 14 (PP14). DESIGN: Prospective controlled clinical study. SETTING: Normal human volunteers in an academic research environment. PARTICIPANTS: Twenty-six fertile, regularly cycling women. INTERVENTIONS: Blood samples were drawn at 0, 3, 6, 9, 12, 18, and 24 hours and then daily for the next 6 days, after a single IM injection of 5,000 IU hCG or saline given on day 5, 7, or 9 after the LH surge, as detected by rapid plasma assays. MAIN OUTCOME MEASURES: Serum P and PP14 measurements. RESULTS: Peak P and PP14 concentrations occurred at 6 hours and 5 days, respectively, after hCG stimulation on luteal phase day 9. Progesterone but not PP14 levels were significantly higher and less variable after hCG than after saline administration on this day. Progesterone responses exceeded 11.0 ng/mL (35.0 nmol/L) in all women, suggesting that this represents the cutoff limit for normal luteal function. Because PP14 responses were highly variable and inconsistent, it was not possible to determine a threshold for normal endometrial function. CONCLUSIONS: Midluteal phase administration of hCG in normal women induces consistent serum P levels > 11.0 ng/mL (35.0 nmol/L) but highly variable PP14 responses.

Adult↗

Serum levels of placental protein 14 do not accurately reflect histologic maturation of the endometrium.

OBJECTIVE: To determine whether serum levels of placental protein 14, a major product of the progesterone-induced secretory endometrium, accurately reflect histologic maturation of the endometrium. METHODS: Daily serum levels of placental protein 14 were compared in 50 normally cycling women with normal or delayed endometrial maturation, as assessed by histologic dating of an endometrial biopsy in the midluteal phase of the same cycle. Ten of these subjects had placental protein 14 measurements but no biopsy in an additional cycle to examine the potential effects of the biopsy on secretion of this protein. RESULTS: Serum placental protein 14 concentrations started to increase 8 days after the LH surge and peaked at similar levels on the first day of the next menses in biopsy and non-biopsy cycles. The biopsy cycles had a shorter luteal phase but a slightly faster increase in placental protein 14 concentrations. Both the integrated secretion of this protein and single measurements on the day of the biopsy or at the onset of the next menses overlapped substantially in women with different degrees of endometrial development, even when differentiation of the endometrium was severely delayed. CONCLUSION: Serum measurements of placental protein 14 do not accurately predict, and thus should not replace, histologic evaluation of the endometrium at nidation.

Abortion, Habitual↗

Measurement of placental protein 14 (PP14) not helpful in predicting infertility or spontaneous abortion.

Placental protein 14 (PP14) can be measured in the serum by radioimmunoassay. The level rises from mid to late luteal phase in a manner similar to the endometrial biopsy. A study was initiated to determine if a clinical association could be found between the late luteal phase serum PP14 level and subsequent pregnancy and spontaneous abortion rate. No difference was found in the preconception PP14 level in patients conceiving versus those not conceiving, nor in those aborting versus those not aborting. A trend toward higher levels in conception versus non-conception cycles was noted, but a large patient group will be needed to demonstrate statistical significance.

Abortion, Spontaneous↗

Role of cigarette smoking on the postmenopausal endometrium during sequential estrogen and progestogen therapy.

OBJECTIVE: To study the effect of cigarette smoking on the endometrial response to sequentially combined hormone replacement therapy. METHODS: Healthy, early postmenopausal women were randomly assigned to three treatment groups: estradiol (E2) sequentially combined with 75 micrograms of levonorgestrel (19), or 150 micrograms of desogestrel (20), or 10 mg of medroxyprogesterone acetate (18). After 2 years of therapy, the hormone effects on the endometrium were assessed by endometrial histology; effects were also analyzed on biochemical markers of secretion, specifically, secretory endometrial protein (placental protein 14) in serum, and E2 dehydrogenase and isocitrate dehydrogenase in endometrial tissue. Information on smoking habits was elicited by questionnaire. RESULTS: Smokers numbered relatively more women with an atrophic endometrium (50 versus 22%) and proportionally fewer with secretory endometrium (50 versus 78%) (P < .05). The level of serum placental protein 14 was correspondingly almost halved in the smokers (P < .001). The influence of smoking was in part caused by a reduced level of serum E2, but primarily by a non-E2-mediated effect. The E2 effect accounted for 38% of the decrease in serum placental protein 14, and the non-E2-mediated smoking effect for 62%. Endometrial E2 and isocitrate dehydrogenase tended to be lower in smokers, but not after adjustment for the reduced serum E2 level. CONCLUSION: We suggest that smokers may benefit from a hormone combination with a higher dose of E2, even higher than expected as seen from the measurement of serum E2.

Desogestrel↗

A prospective controlled study of luteal and endometrial abnormalities in an infertile population.

OBJECTIVE: To investigate whether luteal and endometrial abnormalities occur more frequently in an infertile population and thus contribute to infertility. DESIGN: Prospective controlled clinical study. SETTING: Outpatient clinic in an academic research institution. PARTICIPANTS: Thirty-three fertile controls and 31 infertile women without ovulatory disorders, tubal disease, or male factors. INTERVENTIONS: All women underwent an endometrial biopsy 9 days after the LH surge followed by an IM injection of 5,000 IU hCG. Blood samples were drawn immediately before hCG administration for serum P and placental protein 14 (PP14) measurements, at 6 hours after hCG stimulation for serum P concentrations, and on day 5 after hCG administration for serum PP14 levels. MAIN OUTCOME MEASURES: Histologic dating of the endometrium and serum P and PP14 measurements. RESULTS: Abnormal endometrial biopsies occurred more frequently in infertile (43%) than in fertile women (9%). Except for one case, these specimens were not associated with low hCG-stimulated P levels. Serum PP14 measurements varied widely and did not discriminate subjects with abnormal endometrial development. CONCLUSIONS: Disruption of endometrial maturation without a concomitant defect of the corpus luteum occurs more frequently in an infertile population and thus may contribute to infertility.

Adult↗

[Stimulation trials of trophoblast cells in vitro using PP14].

Cytotrophoblast cells were isolated from human term placenta after cesarean section by fragmentation of villous tissue with trypsin and DNAse I. Trophoblast cells fuse in vitro to syncytiotrophoblast cells and progesteron is released. Placental Protein 14 (PP14) was incubated (300 micrograms/ml PP14 in 6 ml solution (6 x 10(6) cells) with the cytotrophoblast cells. Production of Progesteron is increased in PP14-trophoblast cell cultures compared to untreated trophoblast cells.

Cells, Cultured↗

Production of endometrial placental protein 14 and prolactin by cultured endometrial explants after collagenase and freeze/thaw treatment, and in response to progesterone.

OBJECTIVE: Investigation of methods for maintaining functional endometrial explants in culture after cryopreservation with or without previous enzymatic dispersion of stromal cells and epithelial glands. Such a standardized culture system is a requirement for the development of a non-invasive bioassay for embryo quality in in vitro fertilization programs, a method that will eventually measure endometrial response to embryo conditioned media. METHOD: Culture of mid-luteal phase endometrial biopsies, in the presence of [35S]methionine, with or without prior collagenase treatment and/or storage in liquid nitrogen in the presence of dimethyl sulfoxide. Determination of released de novo synthesized total protein by trichloroacetic acid precipitation of culture media. Measurement, after culture in absence and presence of progesterone, of prolactin and placental protein 14 (PP14) production by sensitive non-isotopic immunoassays. RESULTS: Production of prolactin, but not PP14, was increased by 200 nmol/l progesterone, 2-8-fold after 4 days and 1.5-700-fold after 7 days in culture. After limited collagenase treatment (but without separation of stromal cells from glands), both marker protein productions were similar compared to untreated explants; however, there was no significant stimulation of prolactin by progesterone. After freezing and thawing, production was markedly reduced, particularly from explants frozen following collagenase treatment. CONCLUSIONS: Both stromal and glandular viability are maintained after collagenase treatment but the response to progesterone is lost. Cryopreservation reduced prolactin and PP14 production in subsequent culture. Therefore, novel freezing protocols should be developed which preserve both endometrial structure and function.

Collagenases↗

Serum levels of human placental lactogen, pregnancy-associated plasma protein A and endometrial secretory protein PP14 in first trimester of diabetic pregnancy.

OBJECTIVE: To study maternal serum levels of human placental lactogen (hPL), pregnancy-associated plasma protein A (PAPP-A) and endometrial secretory protein PP14 (PP14) in first trimester of diabetic pregnancy. METHODS: Seventy-nine insulin-dependent diabetic women and 93 normal pregnant women had a venous blood sample drawn in weeks 8-14, ultrasound age. Serum levels were measured by radioimmunoassays and expressed in multiples of the median serum value in normal pregnancy at that ultrasound age. RESULTS: Levels of hPL were significantly lower in diabetic mothers than in controls, z'= -5.502, p<0.00001. Levels of PAPP-A were also significantly lower, z' =2.263, p=0.024, but were significantly less depressed than those of hPL, z'=2.41, p=0.015. The PP14 levels did not deviate from normal. CONCLUSION: In first trimester of diabetic pregnancy there appears to be both a more general depression of trophoblast function, and also a specific depression of the hPL release.

Case-Control Studies↗

Expression of placental protein 14 by the new endometrial cancer cell line MFE-280 in vitro and by endometrial carcinomas in vivo.

MFE-280 endometrial cancer cells express PP14 (placental protein 14) in vitro. PP14 is normally found in the secretory endometrium and in placental tissue. MFE-280 cells, which are tumorigenic in nude mice, were derived from a recurrent, poorly differentiated endometrial carcinoma. The cells were initially grown in suspension culture and later transferred to monolayer cultures. Karyotyping revealed near-diploidy with a complex heterogeneous aberration pattern. MFE-280 cells were positive for the cytokeratins 7, 8, 18 and 19 as well as for vimentin. The expression of PP14 in MFE-280 cells was demonstrated by immunochemistry and reverse transcriptase--polymerase chain reaction. PP14-mRNA was also detected in one out of five endometrial cancer specimen. In tumor tissue the expression of PP14 was not dependent on progestins.

Animals↗