scholarly journals Second trimester levels of maternal serum total activin A and placental inhibin/activin alpha and betaA subunit messenger ribonucleic acids in Down syndrome pregnancy

1998 ◽  
pp. 425-429 ◽  
Author(s):  
GM Lambert-Messerlian ◽  
S Luisi ◽  
P Florio ◽  
V Mazza ◽  
JA Canick ◽  
...  

OBJECTIVES: Previous data have shown that inhibin A (alpha/betaA) is increased about twofold in maternal serum samples from Down syndrome pregnancy. Our objectives were to determine whether activin A (betaA/betaA) was similarly increased in maternal serum from pregnancies affected with fetal Down syndrome, and to investigate whether increased expression of each inhibin/activin subunit occurred in placental tissue from cases of fetal Down syndrome. DESIGN AND METHODS: Maternal serum total activin A levels were measured in 20 cases of fetal Down syndrome and 100 unaffected pregnancy samples. In addition, analysis of inhibin/activin alpha and betaA subunit mRNA levels was performed in placental tissue extracts from six cases of fetal Down syndrome and six tissues with a normal karyotype. RESULTS: The median total activin A level in the Down syndrome cases was 0.82 MoM (multiples of the median); values did not differ significantly (P = 0.36, Mann-Whitney U analysis) from those in unaffected pregnancies. The inhibin alpha subunit/GAPDH mRNA ratio, but not that of betaA subunit/GAPDH mRNA, was significantly greater (P < 0.01, ANOVA) in placental tissue from Down syndrome than in control placental tissue. CONCLUSIONS: Unlike inhibin A, activin A is not significantly increased in Down syndrome relative to unaffected pregnancy. Furthermore, increased amounts of maternal serum inhibin A in Down syndrome pregnancy probably result from increased placental expression of inhibin alpha, but not betaA, subunit.

2002 ◽  
pp. 785-793 ◽  
Author(s):  
NA Bersinger ◽  
N Groome ◽  
S Muttukrishna

OBJECTIVE: Pre-eclampsia is a placental disease of unknown cause. Maternal circulating concentrations of a number of protein markers are altered (mainly increased) in pre-eclampsia in comparison with controls of matched gestational age. Inhibin A and activin A were found to be elevated even before the onset of the disease. The aim of this study was to compare the levels of inhibin A, activin A: follistatin ratio, leptin, pregnancy-associated plasma protein-A (PAPP-A), human placental lactogen (HPL), placenta growth factor (PLGF) and pregnancy-specific beta1-glycoprotein (SP1) in placental extracts of normal pregnant women and pre-eclampsia patients at term. METHODS: Placental tissue from normal pregnancies (n=14) and patients with pre-eclampsia (n=13) were collected at term (> or =37 weeks of gestation) and stored at -80 degrees C. The frozen tissue pieces were homogenised and the above-mentioned proteins were measured by specific enzyme-linked immunosorbent assays. RESULTS: Placental contents of inhibin A and PAPP-A were significantly higher (P<0.05) in pre-eclampsia placental extracts compared with the controls. Activin A:follistatin ratio was higher (23) in pre-eclampsia extracts than in the controls (15). Leptin, PLGF, SP1 and HPL levels were not altered in the term pre-eclampsia placenta. Inhibin A and PAPP-A contents were increased in the placental extracts of pre-eclampsia patients. CONCLUSION: Our data suggest that the placenta, possibly by a compensatory mechanism, is at least in part responsible for the altered serum levels observed in pre-eclampsia.


2001 ◽  
Vol 21 (7) ◽  
pp. 571-574 ◽  
Author(s):  
Kevin Spencer ◽  
Adolfo W. Liao ◽  
Charas Y. T. Ong ◽  
Nicola J. Flack ◽  
Kypros H. Nicolaides

1998 ◽  
Vol 13 (12) ◽  
pp. 3530-3536 ◽  
Author(s):  
P. A. Fowler ◽  
L. W. Evans ◽  
N. P. Groome ◽  
A. Templeton ◽  
P. G. Knight

Reproduction ◽  
2012 ◽  
Vol 143 (5) ◽  
pp. 637-650 ◽  
Author(s):  
J M Young ◽  
S Henderson ◽  
C Souza ◽  
H Ludlow ◽  
N Groome ◽  
...  

Little is known about the role of activin B during folliculogenesis. This study investigated the expression levels of activin/inhibin subunits (βA, βB, and α), steroid enzyme, and gonadotrophin receptors in theca (TC) and granulosa cells (GC) by QPCR and activin A and B and inhibin A protein levels in follicular fluid (FF) of developing sheep follicles during estrus and anestrus. The effect of activin B on androgen production from primary TC cultures in vitro was also assessed. During folliculogenesis, in anestrus and estrus, FF activin B concentrations and thecal and GC activin βB mRNA levels decreased as follicle diameter increased from 1–3 to >6 mm regardless of estrogenic status. Estrogenic preovulatory follicles had reduced concentrations of FF activins B and A, and TC and GCs expressed higher levels of activin βA mRNA at 3–4 mm, and TCs more inhibin α mRNA at >4 mm stages of development compared with nonestrogenic follicles. Activin B decreased androstenedione production from primary TCs in vitro, an effect blocked by inhibin A. Thus, sheep follicles 1–3 mm in diameter contained high FF levels of activin B, which decreased as the follicle size increased, and, like activin A, suppressed thecal androgen production in vitro, an effect blocked by inhibin. Furthermore, the theca of large estrogenic follicles expressed high levels of inhibin α and activin βA mRNA suggesting local thecal derived inhibin A production. This would inhibit the negative effects of thecal activins B and A ensuring maximum androgen production for enhanced estradiol production by the preovulatory follicle(s).


1996 ◽  
Vol 3 (2) ◽  
pp. 58-62 ◽  
Author(s):  
G M Lambert-Messerlian ◽  
J A Canick ◽  
G E Palomaki ◽  
A L Schneyer ◽  
G M Lambert-Messerlian

Objective –To determine the levels of various biochemical forms of the placental protein, inhibin (total inhibin, inhibin A, and α inhibin precursor) and activin in maternal serum samples from fetal Down's syndrome, and to determine which of these analytes most effectively identifies samples from affected pregnancies. Methods –Maternal serum samples were collected from 100 unaffected pregnancies and 20 cases of fetal Down's syndrome during gestational weeks 15–20 for routine triple marker screening, and were stored frozen after clinical assay. Levels of inhibin A, total inhibin, α inhibin precursor (pro-αC), and activin were compared retrospectively in the Down's syndrome cases and control samples. Results –There was no association of the inhibin or activin levels with gestational age or length of freezer storage, and therefore single median values were determined for the unaffected pregnancies for each analyte. Multiples of the unaffected median (MoM) values were calculated for all cases, showing that inhibin A (1.95 MoM) provided the best discrimination between cases and controls, followed by total inhibin (1.37 MoM). Mann-Whitney U analysis showed significant group differences in inhibin A (P = 0.0001) and total inhibin (P = 0.0005). In contrast, α inhibin precursor (0.81 MoM) and activin (1.16 MoM) levels in Down's syndrome cases were not significantly different from those in unaffected patients. Conclusions —Levels of inhibin A and total inhibin, but not α inhibin precursor or activin, are significantly raised in maternal serum from cases of fetal Down's syndrome. These data, taken together, indicate that inhibin A levels are specifically raised in Down's syndrome pregnancy. 45% of the inhibin A levels in the Down's syndrome samples were above the 90th centile of unaffected levels, indicating that inhibin A may be as good a marker as human chorionic gonadotrophin, the most informative serum marker currently in use.


1998 ◽  
Vol 5 (3) ◽  
pp. 115-119 ◽  
Author(s):  
J E Haddow ◽  
G E Palomaki ◽  
G J Knight ◽  
D L Foster ◽  
L M Neveux

Objectives To determine the second trimester Down's syndrome screening performance of maternal serum dimeric inhibin A, both alone and in combination with existing serum markers. Setting A case-control set of serum samples from patients with Down's syndrome (52) and subjects with matched unaffected pregnancies obtained in a previous cohort study before second trimester amniocentesis and karyotyping. The amniocenteses were performed for reasons other than a positive serum screening test result. Methods For each serum from a Down's syndrome pregnancy, five serum samples from pregnancies with a normal karyotype were matched for recruitment centre, gestational age, maternal age, and date of amniocentesis. A specific form of inhibin (dimeric inhibin A) was measured using monoclonal antibodies. Measurements of α fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin and its free β subunit were already available. Screening performance was modelled using distribution variables of the analytes coupled with the 1993 age distribution of pregnant women in the United States. Results The median dimeric inhibin A level was 2.10 times higher in Down's syndrome pregnancies. When dimeric inhibin A was combined with maternal age and three other serum markers (α fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin) the Down's syndrome detection rate increased to 75% (from 66%) at a 5% false positive rate. If dimeric inhibin A could be added for less than &dollar;31 (ranging from &dollar;16 to &dollar;39 depending on the detection rate, markers chosen, and method of dating), the cost of detecting each Down's syndrome pregnancy and the number of procedure related fetal losses would both be reduced. Conclusions The addition of dimeric inhibin A to prenatal screening programmes for Down's syndrome should be considered, or possibly it could be substituted for an existing serum marker. One barrier to implementation in the United States, however, is the unavailability of kits with Food and Drug Administration approval.


2004 ◽  
Vol 128 (4) ◽  
pp. 415-420
Author(s):  
J. Alan Erickson ◽  
Edward R. Ashwood ◽  
Cynthia A. Gin

Abstract Context.—Several studies report the role of dimeric inhibin-A in assessing risk for fetal Down syndrome. The majority, however, use the Serotec inhibin-A assay and not the newer Diagnostic Systems Laboratories inhibin-A enzyme-linked immunosorbent assay (ELISA). Objectives.—To establish normal gestational age day-specific medians, to compare our results against previous studies pertaining to the inhibin-A ELISA, and to evaluate long-term assay performance. Design.—Using the inhibin-A ELISA, 100 specimens were assayed for each completed week of gestation for weeks 15 to 20, 50 specimens for 14 weeks, and 54 specimens for 21 weeks or older. Regressed inhibin-A medians were calculated employing a second-degree polynomial fit of the arithmetic medians. Thereafter, inhibin-A ELISA lot comparisons were performed to evaluate consistency. Results.—Regressed values of 182, 174, 175, 184, 201, and 226 pg/mL resulted for weeks 15 to 20, respectively [pg/mL inhibin-A = 4.1528(gestational age)2 − 136.49(gestational age) + 1294.9]. A comparison with 2 other studies shows our values to be lower overall by 15 ± 11.4% and 16 ± 2.6%. However, variability between kit lots was as high as 30%. Conclusions.—The equation derived provides for the calculation of gestational age day-specific inhibin-A medians for integration into maternal serum screening programs with a subsequent decrease in false-positives expected and observed. Our medians differ considerably from those of other studies, with limited data, using the Diagnostic Systems assay. However, lot changes since the initial analysis have exhibited similar inconsistencies. Therefore, we recommend that others incorporating the assay into their screening programs carefully establish, monitor, and adjust their medians accordingly as a result of potential variations.


Placenta ◽  
1997 ◽  
Vol 18 (8) ◽  
pp. A6
Author(s):  
M. Yamoto ◽  
S. Minami

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Anne-Laure Barbotin ◽  
Ajay Kumar ◽  
Bhanu Kalra ◽  
Gopal Savjani ◽  
Valarie Mitchell ◽  
...  

Abstract Inhibin B measurement by conventional assay(s) may be useful in the assessment of spermatogenesis in infertile male patients, especially in cases of azoospermia. Indeed, numerous previous studies have shown that Inhibin B could be helpful to predict a positive testicular sperm extraction (TESE). However, an undetectable Inhibin B concentration (&lt;10pg/mL) does not predict a TESE failure in all cases. These findings explained that most medical centers have precluded the use of Inhibin B assay in the pre-operative hormonal assessment of azoospermic men. Recently, an ultrasensitive Inhibin B assay has been developed allowing the measurement of concentrations below 10pg/mL. The current study aims to assess the clinical relevance of this new assay in men with azoospermia with undetectable Inhibin B levels by conventional assay(s). Methods: This retrospective study included 71 non-obstructive azoospermic men who had undetectable Inhibin B levels (i.e. &lt;10pg/mL by Gen II ELISA from Beckman Coulter, USA) and who underwent a TESE procedure between 2013 and 2019 in the Lille University Hospital. Serum LH, FSH and testosterone levels were systematically measured by routine immunoassays. Cryopreserved serum samples were used to perform ultrasensitive Inhibin B assay (Ultrasensitive Inhibin B, AL-195, Ansh Labs, USA). Additional hormonal assays including Inhibin A, Activin B and Activin A were performed on available subset of samples. Results: The TESE was successful, allowing sperm cryopreservation in 32.5 % (25/71) of the cases. No significant statistical difference was found in FSH, LH, or testosterone levels between patients with positive or negative TESE. By contrast, men with positive TESE had more than twice higher serum ultrasensitive Inhibin B levels (median 5.03pg/mL [1.93-8.5] vs. 2.19pg/mL [0.2-4.72], p=0.006). An ultrasensitive Inhibin B serum level &gt;3.67 pg/mL (determined by ROC analysis) was associated with increased odds ratio (OR= 4.82; 95% CI: 1.647-12.93) for positive TESE. Inhibin A, Activin B and Activin A serum concentrations did not differ significantly between the two groups. Conclusion: FSH measurement which is routinely performed in men with azoospermia was not predictive of successful TESE whereas, Inhibin B was found to be a valuable marker in predicting TESE success in this population using ultrasensitive Inhibin B assay.


2001 ◽  
Vol 185 (6) ◽  
pp. S79 ◽  
Author(s):  
Thomas Lee ◽  
Erik Leshane ◽  
Geralyn Messerlian ◽  
Jacob Canick ◽  
Marshall Carpenter ◽  
...  

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