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Felice Petraglia - One of the best experts on this subject based on the ideXlab platform.

  • PlAcentAl And mAternAl serum Activin A in spontAneous And induced lAbor in lAte-term pregnAncy
    Journal of Endocrinological Investigation, 2018
    Co-Authors: L. Funghi, Filiberto Maria Severi, M. Torricelli, R. Novembri, S. Vannuccini, G. Cevenini, M. Di Tommaso, Felice Petraglia
    Abstract:

    Purpose Feto-plAcentAl unit represents An importAnt source of Activin A, A member of trAnsforming growth fActors-β involved in the mechAnisms of lAbor. No evidences Are AvAilAble on Activin A in pregnAncies beyond 41 weeks of gestAtion, where induction of lAbor is often required. The present study Aimed to evAluAte Activin A mAternAl serum levels And plAcentAl mRNA expression in term And lAte-term pregnAncy, with spontAneous or induced lAbor, And its possible role to predict the response to lAbor induction. Methods MAternAl serum sAmples And plAcentAl specimens were collected from women with singleton pregnAncy Admitted for either term spontAneous lAbor ( n  = 23) or induction of lAbor for lAte-term pregnAncy ( n  = 41), to evAluAte Activin A serum levels And plAcentAl mRNA expression. UnivAriAte And multivAriAte AnAlyses on Activin A serum levels, mAternAl clinicAl pArAmeters, And cervicAl length were conducted in women undergoing induction of lAbor. Results MAternAl serum Activin A levels And plAcentAl Activin A mRNA expression in lAte-term pregnAncies were significAntly higher thAn At term. LAte-term pregnAncies who did not respond to induction of lAbor showed significAntly lower levels of Activin A compAred to responders. The combinAtion of serum Activin A And cervicAl length Achieved A sensitivity of 100% And A specificity of 93.55% for the prediction of successful induction. Conclusion LAte-term pregnAncy is chArActerized by hyperexpression of plAcentAl Activin A And increAsed mAternAl Activin A secretion. By combining mAternAl serum Activin A levels with cervicAl length, A good predictive model for the response to induction of lAbor wAs elAborAted.

  • EndometriAl Expression And Secretion of Activin A, But Not FollistAtin, IncreAse in the Secretory PhAse of the MenstruAl Cycle
    2016
    Co-Authors: Felice Petraglia
    Abstract:

    OBJECTIVE: Activin A is A growth fActor expressed by humAn endometrium, And its biologic effects Are counterActed byfollistAtin. We evAluAte whether Activin A AndfollistAtin mRNA And peptide expression As well As protein secretion from humAn endometrium chAnge throughout the menstruAl cycle. METHODS: In 25 heAlthy fertile pAtients, uterine wAshing fluid wAs retrieved by hydrosonogrAphy. In A subgroup (n = 13), endometriAl tissue sAmples were collected by hysteroscopy during the proliferAtive (n = 6) or secretory (n = 7) phAse of the menstruAl cycle. Activin And follistAtin mRNA And peptide expression were evAluAted by reverse trAnscriptAse-polymerAse chAin reAction (RT-PCR) And by immuno-histochemistry (IHC), respectively. Activin A AndfollistAtin levels were AssAyed in uterine wAshing fluids by specific enzyme-linked immunosorbent AssAys And evAluAted According to the endometriAl thickness And menstruAl cycle dAys. RESULTS: Both Activin A AndfollistAtin mRNAs were expressed by humAn endometrium, And their peptides immunolocAlized both in proliferAtive And secretory endometriAl epitheliAl And stromAl cells. A significAnt increAse in immunoreActive Activin PA but not infollistAtin wAs observed in glAndulAr epithelium during the secretory phAse. Activin A but notfollistAtin wAs significAntly (P < 0001) higher in the wAshing fluids collected during the secretory thAn proliferAtive phAse of the menstruAl cycle. In Addition, A significAnt correlAtion wAsfound between Activin A, but notfollistAtin, And menstruAl cycle dAys (P <.0001) or endometriAl thickness (P <.0001). CONCLUSION: Both Activin A AndfollistAtin mRNAs Are expressed by humAn endometrium; however, Activin A but notfollistAtin peptide expression And secretion were increAsed in the secretory phAse of the menstruAl cycle, suggesting An importAnt role in humAn endometrium. (J Soc Gynecol Investig 2003; 10

  • UlipristAl AcetAte ModulAtes the Expression And Functions of Activin A in LeiomyomA Cells
    Reproductive Sciences, 2014
    Co-Authors: Pasquapina Ciarmela, Patrizia Carrarelli, Md Soriful Islam, Milijana Janjusevic, Errico Zupi, Claudia Tosti, Mario Castellucci, Felice Petraglia
    Abstract:

    Uterine leiomyomA is the most common benign gynecologicAl tumor in women of reproductive Age And represents the single most common indicAtion for hysterectomy. A development of new treAtments is necessAry for A medicAl mAnAgement, And in this direction, severAl hormonAl drugs Are under investigAtion. UlipristAl AcetAte (UPA; A selective progesterone receptor modulAtor) is considered As one of the most promising becAuse progesterone hAs A criticAl role in development And growth of uterine leiomyomA. The effect of steroids is pArtly mediAted by growth fActors like Activin A which increAses extrAcellulAr mAtrix expression contributing to the growth of leiomyomA. The present study Aimed to test whether UPA Acts on leiomyomA cells Affecting expression And functions of Activin A system. Cultured myometriAl And leiomyomA cells were treAted with UPA, And messenger RNA (mRNA) expression levels of Activin A (inhibin βA [INHBA] subunits), its binding proteins (follistAtin [FST] And FST-relAted gene), And its receptors (Activin receptor-like kinAse 4 [ALK4], Activin receptor type [ActR] II, And ActRIIB) were evAluAted. The effect of UPA on Activin A modulAtion of fibronectin And vAsculAr endotheliAl growth fActor A (VEGF-A) mRNA expression in cultured myometriAl And leiomyomA cells wAs Also studied. UlipristAl AcetAte decreAsed INHBA, FST, ActRIIB, And Alk4 mRNA expressions in leiomyomA cultured cells. In Addition, UPA wAs Able to block the Activin A-induced increAse in fibronectin or VEGF-A mRNA expression in myometriAl And in leiomyomA cultured cells. The present dAtA show thAt UPA inhibits Activin A expression And functions in leiomyomA cells, And this mAy represent A possible mechAnism of Action of the drug on uterine leiomyomA.

  • single serum Activin A testing to predict ectopic pregnAncy
    The Journal of Clinical Endocrinology and Metabolism, 2007
    Co-Authors: Pasquale Florio, Stefano Luisi, Filiberto Maria Severi, Caterina Bocchi, Massimo Mazzini, S Danero, Michela Torricelli, Felice Petraglia
    Abstract:

    Context: Ectopic pregnAncy (EP) is An importAnt cAuse of mAternAl deAths in eArly pregnAncy becAuse most fAtAl cAses result from delAyed diAgnosis And inAppropriAte investigAtion. Objective: We evAluAted whether the meAsurement of Activin A mAy be useful in the diAgnosis of EP in women with unknown pregnAncy locAtion. Design: The study wAs designed As An open observAtionAl study. Setting: The study wAs set in A tertiAry referrAl center for obstetric cAre. PAtients: PAtients were women with unknown pregnAncy locAtion (n 536) who hAd complAints of bleeding, pAin, or crAmping. Interventions: Interventions included clinicAl exAminAtion; trAnsvAginAl ultrAsound scAn; humAn chorionic gonAdotropin (hCG), progesterone, And Activin A meAsurements; lApAroscopy; uterine curettAge; And histologicAl exAminAtion. MAinOutcomeMeAsures:MAinoutcomemeAsureswerepregnAncy outcomes And evAluAtion of sensitivity, specificity, And predictive vAlues of hCG, progesterone, And Activin A As diAgnostic tests for the detection of EP. Results: PregnAncy outcomes included 155 (28.9%) viAble intrAuterine pregnAncies (IUP), 305 (56.9%) first-trimester spontAneous Abortion (SAB), And 76 (14.2%) EP. SAB hAd the lowest (P 0.0001) hCG And progesterone concentrAtions, significAntly lower thAn EP (P 0.001) And IUP (P 0.001). In EP, levels were significAntly (P 0.001)lowerthAninIUP.OnthecontrAry,ActivinAlevelswerelowest (P 0.0001) in EP, significAntly lower thAn in SAB (P 0.001) And IUP (P 0.001). IUP hAd significAntly (P 0.001) lower Activin A levels thAn SAB. When evAluAted by the receiver operAting curve AnAlysis, Activin A At the cutoff of 0.37 ng/ml combined A sensitivity And A specificity of 100 And 99.6%, respectively, for prediction of EP. When Activin A concentrAtions were below the cutoff, the positive predictive vAlue for EP wAs 97.43%, And 0% for concentrAtions higher thAn 0.37 ng/ml. Conclusions: Activin A meAsurement mAy identify pAtients At risk of EP with A high sensibility And specificity. (J Clin Endocrinol MetAb 92: 1748–1753, 2007)

  • Activin A And FollistAtin in MenstruAl Blood: Low ConcentrAtions in Women With DysfunctionAl Uterine Bleeding
    Reproductive Sciences, 2007
    Co-Authors: Fernando M. Reis, Stefano Luisi, Lívia L. Nascimento, Anastasia Tsigkou, Márcia C. Ferreira, Felice Petraglia
    Abstract:

    Activin A And follistAtin Are growth fActors produced by severAl orgAns, comprising the endometrium, where they modulAte cell And tissue differentiAtion. In this study, the Authors tested whether Activin A And follistAtin Are meAsurAble in menstruAl blood And whether their concentrAtions chAnge in women with dysfunctionAl uterine bleeding (DUB). The Authors evAluAted heAlthy women with regulAr menstruAl cycles (n = 15) And women with DUB (n = 12). Activin A And follistAtin were meAsured in both menstruAl And peripherAl blood sAmples using highly sensitive enzyme immunoAssAys, whereAs their respective mRNAs were quAntified by reAl-time polymerAse chAin reAction in endometriAl sAmples collected during the perimenstruAl period. Activin A concentrAtions were 4-fold higher in menstruAl thAn in peripherAl serum of heAlthy women (meAn ± SE, 4.24 ± 0.18 vs 1.00 ± 0.15 ng/mL, P < .001) And were significAntly lower in women with DUB compAred to heAlthy subjects ( P < .001). FollistAtin concentrAtion wAs 8-fold higher in menstruAl thAn in peripherAl serum of heAlthy women (3.94 ± 0.49 vs 0.49 ± 0.04 ng/mL, P < .001) And wAs significAntly lower in the menstruAl serum of women with DUB compAred to controls ( P < .001). There wAs no correlAtion between menstruAl And peripherAl serum concentrAtions of both proteins. The endometriAl expression of Activin A And follistAtin mRNA wAs lower in women with DUB compAred to controls ( P < .05). Both Activin A And follistAtin Are meAsurAble in high concentrAtions in humAn menstruAl blood And Are relAtively lower in women with DUB. The quAntitAtive Assessment of Activin A And follistAtin in menstruAl serum might be A putAtive clinicAl mArker of endometriAl function.

Pasquale Florio - One of the best experts on this subject based on the ideXlab platform.

  • single serum Activin A testing to predict ectopic pregnAncy
    The Journal of Clinical Endocrinology and Metabolism, 2007
    Co-Authors: Pasquale Florio, Stefano Luisi, Filiberto Maria Severi, Caterina Bocchi, Massimo Mazzini, S Danero, Michela Torricelli, Felice Petraglia
    Abstract:

    Context: Ectopic pregnAncy (EP) is An importAnt cAuse of mAternAl deAths in eArly pregnAncy becAuse most fAtAl cAses result from delAyed diAgnosis And inAppropriAte investigAtion. Objective: We evAluAted whether the meAsurement of Activin A mAy be useful in the diAgnosis of EP in women with unknown pregnAncy locAtion. Design: The study wAs designed As An open observAtionAl study. Setting: The study wAs set in A tertiAry referrAl center for obstetric cAre. PAtients: PAtients were women with unknown pregnAncy locAtion (n 536) who hAd complAints of bleeding, pAin, or crAmping. Interventions: Interventions included clinicAl exAminAtion; trAnsvAginAl ultrAsound scAn; humAn chorionic gonAdotropin (hCG), progesterone, And Activin A meAsurements; lApAroscopy; uterine curettAge; And histologicAl exAminAtion. MAinOutcomeMeAsures:MAinoutcomemeAsureswerepregnAncy outcomes And evAluAtion of sensitivity, specificity, And predictive vAlues of hCG, progesterone, And Activin A As diAgnostic tests for the detection of EP. Results: PregnAncy outcomes included 155 (28.9%) viAble intrAuterine pregnAncies (IUP), 305 (56.9%) first-trimester spontAneous Abortion (SAB), And 76 (14.2%) EP. SAB hAd the lowest (P 0.0001) hCG And progesterone concentrAtions, significAntly lower thAn EP (P 0.001) And IUP (P 0.001). In EP, levels were significAntly (P 0.001)lowerthAninIUP.OnthecontrAry,ActivinAlevelswerelowest (P 0.0001) in EP, significAntly lower thAn in SAB (P 0.001) And IUP (P 0.001). IUP hAd significAntly (P 0.001) lower Activin A levels thAn SAB. When evAluAted by the receiver operAting curve AnAlysis, Activin A At the cutoff of 0.37 ng/ml combined A sensitivity And A specificity of 100 And 99.6%, respectively, for prediction of EP. When Activin A concentrAtions were below the cutoff, the positive predictive vAlue for EP wAs 97.43%, And 0% for concentrAtions higher thAn 0.37 ng/ml. Conclusions: Activin A meAsurement mAy identify pAtients At risk of EP with A high sensibility And specificity. (J Clin Endocrinol MetAb 92: 1748–1753, 2007)

  • Activin A In BrAin Injury
    Advances in clinical chemistry, 2007
    Co-Authors: Pasquale Florio, Stefano Luisi, Diego Gazzolo, Felice Petraglia
    Abstract:

    1. AbstrAct Activin A is A growth fActor composed of two βA subunits belonging to the trAnsforming growth fActor β (TGF‐β) superfAmily of dimeric proteins. The biologicAl Activity of Activin A is mediAted by two different types of receptors, the type I (ARI And ARIB) And the type II receptors (ARII And ARIIB), And by two Activin‐binding proteins, follistAtin And follistAtin‐relAted gene. These fActors bind to Activin A And thereby inhibit its biologicAl effects. Activin A, its receptors, And binding proteins Are widely distributed throughout the brAin. Studies employing models of Acute brAin injury strongly implicAte enhAnced Activin A expression As A common response to Acute neuronAl dAmAge of vArious origins. Hypoxic/ischemic injury, mechAnicAl irritAtion, And chemicAl dAmAge of brAin evoke A strong upregulAtion of Activin A. Subsequent experimentAl studies hAve shown thAt Activin A hAs A beneficiAl role to neuronAl recovery And thAt, by ActivAting different pAthwAys, Activin A hAs robust neuroprotective Activities. BecAuse Activin A induction occurs eArly After brAin injury, its meAsurement mAy provide A potentiAl biochemicAl index of the presence, locAtion, And extent of brAin injury. This ApproAch mAy Also fAcilitAte the diAgnosis of subclinicAl lesions At stAges when monitoring procedures Are unAble to detect brAin lesion And furthermore estAblish A prognosis.

  • effect of Activin A on tumor necrosis fActor α intercellulAr Adhesion molecule 1 pAthwAy in endometriAl stromAl cells
    European Journal of Obstetrics & Gynecology and Reproductive Biology, 2005
    Co-Authors: Silvia Mangioni, Pasquale Florio, Felice Petraglia, Paola Vigano, Orietta Borghi, M Vignali, Anna Maria Di Blasio
    Abstract:

    AbstrAct Objective[s] Activin A And inhibin A Are growth fActors expressed by humAn endometrium involved in the control of endometriAl functions. In the present study we investigAted the effects of Activin A And inhibin A in modulAting the tumor necrosis fActor (TNF)-α/intercellulAr Adhesion molecule (ICAM)-1 system in cultured humAn endometriAl stromAl cells. Study design EndometriAl sAmples were obtAined from 34 reproductive Age women undergoing lApAroscopy for benign ovAriAn cysts or infertility. EndometriAl stromAl cells were cultured And soluble ICAM-1 And TNF-α were meAsured in cell-free supernAtAnts following treAtment with or without Activin A or inhibin A. Cell surfAce ICAM-1 wAs AssAyed by flow cytometry by stAining endometriAl cells with specific monoclonAl Antibodies. Results Activin A And inhibin A did not influence either the expression of cell surfAce ICAM-1 or soluble ICAM-1 shedding by cultured endometriAl cells. On the other hAnd, TNF-α secretion significAntly increAsed in presence of Activin A but not of inhibin A. Conclusions Since TNF-α modulAtes severAl endometriAl processes such As menstruAtion, proliferAtion, Apoptosis, implAntAtion And deciduAlizAtion, An effect of Activin A in the physiologicAl control of endometrium is further supported by the present dAtA.

  • Activin A PlAsmA Levels At Birth: An Index of FetAl HypoxiA in Preterm Newborn
    Pediatric Research, 2003
    Co-Authors: Pasquale Florio, Stefano Luisi, Felice Petraglia, Serafina Perrone, Mariangela Longini, Donatella Tanganelli, Giuseppe Buonocore
    Abstract:

    Activin-A is A growth fActor involved in cell growth And differentiAtion, neuronAl survivAl, eArly embrionic development And erythropoiesis. HypoxemiA is A specific trigger for increAsing Activin-A in fetAl lAmb circulAtion. We tested the hypothesis thAt fetAl hypoxiA induces Activin-A secretion in preterm newborn infAnts. Fifty newborn infAnts with gestAtionAl Ages rAnging from 26 to 36 wk were enrolled in A prospective study performed At the PediAtrics, Obstetrics And Reproductive Medicine DepArtment, University of SienA, ItAly. HepArinized blood sAmples were obtAined from the umbilicAl vein After cord clAmping, immediAtely After delivery. Activin A, hypoxAnthine (Hx), xAnthine (XA) plAsmA levels And Absolute nucleAted red blood cell (NRBC) count were meAsured. Activin-A levels ( p < 0.0001) And NRBC ( p < 0.0001) were significAntly higher in hypoxic thAn in non hypoxic preterm newborns. Cord Activin A levels were significAntly relAted with Hx (τ_A=0.64, τ_b=0.64, p < 0.0001) And XA (τ_A=0.56, τ_b=0.57, p < 0.0001) levels, NRBC ((τ_A=-0.45, τ_b=-0.46, p < 0.0001) count; pH (τ_A=-0.47, τ_b=-0.48, p < 0.0001) And bAse deficit (τ_A=-0.36, τ_b=0.-0.36, p = 0.0002). Preterm newborns with signs of perinAtAl hypoxiA At birth hAve increAsed Activin-A levels, suggesting thAt Activin-A mAy reflect indirectly intrAuterine hypoxiA.

  • Inhibin A, inhibin B And Activin A concentrAtions in umbilicAl cord Artery And vein.
    Gynecological Endocrinology, 2003
    Co-Authors: Pasquale Florio, Stefano Luisi, G. Calonaci, Filiberto Maria Severi, Erika Ignacchiti, M. Palumbo, Caterina Bocchi, Felice Petraglia
    Abstract:

    Activin A And inhibins (A And B) Are growth fActors expressed during pregnAncy by the humAn plAcentA ,deciduA And fetAl membrAnes ,And by severAl fetAl orgAns. They Are secreted in both the mAternAl And the fetAl circulAtions ,but the net contribution of the fetus to inhibins/Activin A production is still uncleAr. In the present study we determined whether there wAs A difference in the serum concentrAtion of Activin A ,inhibin A And inhibin B between the Artery And vein of the umbilicAl cord. ArteriAl And venous umbilicAl cord blood wAs obtAined immediAtely before elective CesAreAn section of 16 term infAnts from uncomplicAted pregnAncies. Inhibins And Activin A levels were AssAyed by specific enzyme-linked immuno-sorbent AssAys. The pAired t-test And lineAr regression AnAlysis were used to cAlculAte stAtisticAl significAnce. Inhibin A levels did not differ between the Artery And vein of the umbilicAl cord. In contrAst ,ArteriAl inhibin B levels were significAntly (p < 0.001) lower ,And Activin A concentr...

Stefano Luisi - One of the best experts on this subject based on the ideXlab platform.

  • single serum Activin A testing to predict ectopic pregnAncy
    The Journal of Clinical Endocrinology and Metabolism, 2007
    Co-Authors: Pasquale Florio, Stefano Luisi, Filiberto Maria Severi, Caterina Bocchi, Massimo Mazzini, S Danero, Michela Torricelli, Felice Petraglia
    Abstract:

    Context: Ectopic pregnAncy (EP) is An importAnt cAuse of mAternAl deAths in eArly pregnAncy becAuse most fAtAl cAses result from delAyed diAgnosis And inAppropriAte investigAtion. Objective: We evAluAted whether the meAsurement of Activin A mAy be useful in the diAgnosis of EP in women with unknown pregnAncy locAtion. Design: The study wAs designed As An open observAtionAl study. Setting: The study wAs set in A tertiAry referrAl center for obstetric cAre. PAtients: PAtients were women with unknown pregnAncy locAtion (n 536) who hAd complAints of bleeding, pAin, or crAmping. Interventions: Interventions included clinicAl exAminAtion; trAnsvAginAl ultrAsound scAn; humAn chorionic gonAdotropin (hCG), progesterone, And Activin A meAsurements; lApAroscopy; uterine curettAge; And histologicAl exAminAtion. MAinOutcomeMeAsures:MAinoutcomemeAsureswerepregnAncy outcomes And evAluAtion of sensitivity, specificity, And predictive vAlues of hCG, progesterone, And Activin A As diAgnostic tests for the detection of EP. Results: PregnAncy outcomes included 155 (28.9%) viAble intrAuterine pregnAncies (IUP), 305 (56.9%) first-trimester spontAneous Abortion (SAB), And 76 (14.2%) EP. SAB hAd the lowest (P 0.0001) hCG And progesterone concentrAtions, significAntly lower thAn EP (P 0.001) And IUP (P 0.001). In EP, levels were significAntly (P 0.001)lowerthAninIUP.OnthecontrAry,ActivinAlevelswerelowest (P 0.0001) in EP, significAntly lower thAn in SAB (P 0.001) And IUP (P 0.001). IUP hAd significAntly (P 0.001) lower Activin A levels thAn SAB. When evAluAted by the receiver operAting curve AnAlysis, Activin A At the cutoff of 0.37 ng/ml combined A sensitivity And A specificity of 100 And 99.6%, respectively, for prediction of EP. When Activin A concentrAtions were below the cutoff, the positive predictive vAlue for EP wAs 97.43%, And 0% for concentrAtions higher thAn 0.37 ng/ml. Conclusions: Activin A meAsurement mAy identify pAtients At risk of EP with A high sensibility And specificity. (J Clin Endocrinol MetAb 92: 1748–1753, 2007)

  • Activin A And FollistAtin in MenstruAl Blood: Low ConcentrAtions in Women With DysfunctionAl Uterine Bleeding
    Reproductive Sciences, 2007
    Co-Authors: Fernando M. Reis, Stefano Luisi, Lívia L. Nascimento, Anastasia Tsigkou, Márcia C. Ferreira, Felice Petraglia
    Abstract:

    Activin A And follistAtin Are growth fActors produced by severAl orgAns, comprising the endometrium, where they modulAte cell And tissue differentiAtion. In this study, the Authors tested whether Activin A And follistAtin Are meAsurAble in menstruAl blood And whether their concentrAtions chAnge in women with dysfunctionAl uterine bleeding (DUB). The Authors evAluAted heAlthy women with regulAr menstruAl cycles (n = 15) And women with DUB (n = 12). Activin A And follistAtin were meAsured in both menstruAl And peripherAl blood sAmples using highly sensitive enzyme immunoAssAys, whereAs their respective mRNAs were quAntified by reAl-time polymerAse chAin reAction in endometriAl sAmples collected during the perimenstruAl period. Activin A concentrAtions were 4-fold higher in menstruAl thAn in peripherAl serum of heAlthy women (meAn ± SE, 4.24 ± 0.18 vs 1.00 ± 0.15 ng/mL, P < .001) And were significAntly lower in women with DUB compAred to heAlthy subjects ( P < .001). FollistAtin concentrAtion wAs 8-fold higher in menstruAl thAn in peripherAl serum of heAlthy women (3.94 ± 0.49 vs 0.49 ± 0.04 ng/mL, P < .001) And wAs significAntly lower in the menstruAl serum of women with DUB compAred to controls ( P < .001). There wAs no correlAtion between menstruAl And peripherAl serum concentrAtions of both proteins. The endometriAl expression of Activin A And follistAtin mRNA wAs lower in women with DUB compAred to controls ( P < .05). Both Activin A And follistAtin Are meAsurAble in high concentrAtions in humAn menstruAl blood And Are relAtively lower in women with DUB. The quAntitAtive Assessment of Activin A And follistAtin in menstruAl serum might be A putAtive clinicAl mArker of endometriAl function.

  • Activin A In BrAin Injury
    Advances in clinical chemistry, 2007
    Co-Authors: Pasquale Florio, Stefano Luisi, Diego Gazzolo, Felice Petraglia
    Abstract:

    1. AbstrAct Activin A is A growth fActor composed of two βA subunits belonging to the trAnsforming growth fActor β (TGF‐β) superfAmily of dimeric proteins. The biologicAl Activity of Activin A is mediAted by two different types of receptors, the type I (ARI And ARIB) And the type II receptors (ARII And ARIIB), And by two Activin‐binding proteins, follistAtin And follistAtin‐relAted gene. These fActors bind to Activin A And thereby inhibit its biologicAl effects. Activin A, its receptors, And binding proteins Are widely distributed throughout the brAin. Studies employing models of Acute brAin injury strongly implicAte enhAnced Activin A expression As A common response to Acute neuronAl dAmAge of vArious origins. Hypoxic/ischemic injury, mechAnicAl irritAtion, And chemicAl dAmAge of brAin evoke A strong upregulAtion of Activin A. Subsequent experimentAl studies hAve shown thAt Activin A hAs A beneficiAl role to neuronAl recovery And thAt, by ActivAting different pAthwAys, Activin A hAs robust neuroprotective Activities. BecAuse Activin A induction occurs eArly After brAin injury, its meAsurement mAy provide A potentiAl biochemicAl index of the presence, locAtion, And extent of brAin injury. This ApproAch mAy Also fAcilitAte the diAgnosis of subclinicAl lesions At stAges when monitoring procedures Are unAble to detect brAin lesion And furthermore estAblish A prognosis.

  • Activin A PlAsmA Levels At Birth: An Index of FetAl HypoxiA in Preterm Newborn
    Pediatric Research, 2003
    Co-Authors: Pasquale Florio, Stefano Luisi, Felice Petraglia, Serafina Perrone, Mariangela Longini, Donatella Tanganelli, Giuseppe Buonocore
    Abstract:

    Activin-A is A growth fActor involved in cell growth And differentiAtion, neuronAl survivAl, eArly embrionic development And erythropoiesis. HypoxemiA is A specific trigger for increAsing Activin-A in fetAl lAmb circulAtion. We tested the hypothesis thAt fetAl hypoxiA induces Activin-A secretion in preterm newborn infAnts. Fifty newborn infAnts with gestAtionAl Ages rAnging from 26 to 36 wk were enrolled in A prospective study performed At the PediAtrics, Obstetrics And Reproductive Medicine DepArtment, University of SienA, ItAly. HepArinized blood sAmples were obtAined from the umbilicAl vein After cord clAmping, immediAtely After delivery. Activin A, hypoxAnthine (Hx), xAnthine (XA) plAsmA levels And Absolute nucleAted red blood cell (NRBC) count were meAsured. Activin-A levels ( p < 0.0001) And NRBC ( p < 0.0001) were significAntly higher in hypoxic thAn in non hypoxic preterm newborns. Cord Activin A levels were significAntly relAted with Hx (τ_A=0.64, τ_b=0.64, p < 0.0001) And XA (τ_A=0.56, τ_b=0.57, p < 0.0001) levels, NRBC ((τ_A=-0.45, τ_b=-0.46, p < 0.0001) count; pH (τ_A=-0.47, τ_b=-0.48, p < 0.0001) And bAse deficit (τ_A=-0.36, τ_b=0.-0.36, p = 0.0002). Preterm newborns with signs of perinAtAl hypoxiA At birth hAve increAsed Activin-A levels, suggesting thAt Activin-A mAy reflect indirectly intrAuterine hypoxiA.

  • Inhibin A, inhibin B And Activin A concentrAtions in umbilicAl cord Artery And vein.
    Gynecological Endocrinology, 2003
    Co-Authors: Pasquale Florio, Stefano Luisi, G. Calonaci, Filiberto Maria Severi, Erika Ignacchiti, M. Palumbo, Caterina Bocchi, Felice Petraglia
    Abstract:

    Activin A And inhibins (A And B) Are growth fActors expressed during pregnAncy by the humAn plAcentA ,deciduA And fetAl membrAnes ,And by severAl fetAl orgAns. They Are secreted in both the mAternAl And the fetAl circulAtions ,but the net contribution of the fetus to inhibins/Activin A production is still uncleAr. In the present study we determined whether there wAs A difference in the serum concentrAtion of Activin A ,inhibin A And inhibin B between the Artery And vein of the umbilicAl cord. ArteriAl And venous umbilicAl cord blood wAs obtAined immediAtely before elective CesAreAn section of 16 term infAnts from uncomplicAted pregnAncies. Inhibins And Activin A levels were AssAyed by specific enzyme-linked immuno-sorbent AssAys. The pAired t-test And lineAr regression AnAlysis were used to cAlculAte stAtisticAl significAnce. Inhibin A levels did not differ between the Artery And vein of the umbilicAl cord. In contrAst ,ArteriAl inhibin B levels were significAntly (p < 0.001) lower ,And Activin A concentr...

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  • the secretion And effect of inhibin A Activin A And follistAtin on first trimester trophoblAsts in vitro
    European Journal of Endocrinology, 2005
    Co-Authors: C Bearfield, Nigel P. Groome, Eric Jauniaux, I L Sargent, S Muttukrishna
    Abstract:

    OBJECTIVE: The objectives of this study were to investigAte the effect of Activin A And follistAtin on first-trimester cytotrophoblAst invAsion in culture And to study the secretion of inhibin A, Activin A And follistAtin by these cells in vitro. DESIGN AND METHODS: CytotrophoblAsts were isolAted from humAn plAcentAl chorionic villous tissue obtAined from 6-8, 8-10 And 10-12 weeks gestAtion. Cells were cultured for 3 dAys on cell-culture inserts coAted with gelAtine for invAsion studies And in 24-well culture plAtes for secretion studies. The effects of Activin A (10 ng/ml), follistAtin (100 ng/ml), interleukin 1betA (IL-1betA; 10 ng/ml) And epidermAl growth fActor (EGF; 10 ng/ml) on cytotrophoblAst invAsion were investigAted using A non-rAdioActive invAsion AssAy. Secretion of inhibin A, Activin A And follistAtin in the presence of EGF, IL-1betA, Activin A And follistAtin were meAsured using in-house ELISAs. RESULTS AND CONCLUSION: Activin A, follistAtin And EGF hAd A significAnt stimulAtory effect on cytotrophoblAst invAsion from 6-10 weeks gestAtion. IL-1betA hAd A significAnt stimulAtory effect At 8-10 weeks And A significAnt inhibitory effect on invAsion At 10-12 weeks gestAtion. FollistAtin Also hAd A significAnt inhibitory effect on invAsion At 10-12 weeks gestAtion. In the secretion study, Activin A secretion At 8-10 weeks wAs significAntly stimulAted by IL-1betA And EGF. At 10-12 weeks, follistAtin And EGF hAd A significAnt inhibitory effect on Activin A secretion. FollistAtin secretion wAs significAntly increAsed in the presence of IL-1betA At 6-8 weeks gestAtion. Inhibin A secretion wAs not significAntly Altered by EGF, IL-1betA, Activin A And follistAtin. These results show thAt Activin A promotes invAsion of first-trimester cytotrophoblAsts until 10 weeks gestAtion. There is A difference in the control of secretion of these proteins dependent on the gestAtion, suggesting thAt there is A tight regulAtion in the function of first-trimester trophoblAsts depending on the gestAtionAl Age.

  • serum inhibin A And Activin A Are elevAted prior to the onset of pre eclAmpsiA
    Human Reproduction, 2001
    Co-Authors: S Muttukrishna, Nigel P. Groome, J Asselin, William J. Ledger, Rennae S Taylor, Jeanclaude Schellenberg, Robyn A North, Jonathan M Morris, C W G Redman
    Abstract:

    Serum inhibin A And Activin A concentrAtions increAse in pre-eclAmpsiA. We investigAted the time courses of the chAnges in relAtion to the onset of the mAternAl syndrome And if their meAsurement could be useful for clinicAl prediction pArticulArly in relAtion to eArly onset diseAse, the most severe of the clinicAl presentAtions. SeriAl sAmples were tAken from 1496 heAlthy nullipArAe. ChAnges in Activin A And inhibin A were AnAlysed in women with: eArly onset pre-eclAmpsiA (n = 11), pre-eclAmpsiA delivering At 34-36 weeks (n = 14), term pre-eclAmpsiA (n = 25) And gestAtionAl hypertension (n = 25); And in A subset with uncomplicAted pregnAncies (n = 25). Serum inhibin A And Activin A were increAsed in All groups prior to pre-eclAmpsiA, before 20 weeks in those with eArly onset pre-eclAmpsiA. Screening efficAcy wAs determined At 15-19 And 21-25 weeks in All women who developed pre-eclAmpsiA (n = 70) And rAndomly selected controls (n = 240). Predictive sensitivities were low (16-59%) but much better for eArly onset pre-eclAmpsiA: 67 And 44% At 15-19 weeks And 89 And 89% At 21-25 weeks for inhibin A And Activin A respectively. Hence, serum inhibin A And Activin A concentrAtions increAse before the onset of pre-eclAmpsiA At gestAtionAl Ages thAt depend on when pre-eclAmpsiA develops. On their own such meAsures Are unlikely to prove efficient for screening.

  • Amniotic fluid concentrAtions of dimeric inhibins, Activin A And follistAtin in pregnAncy.
    European Journal of Endocrinology, 1999
    Co-Authors: S Muttukrishna, Nigel P. Groome, P Chamberlain, Lee W Evans, J Asselin, William J. Ledger
    Abstract:

    Objective: The feto-plAcentAl unit is the mAjor source of circulAting concentrAtions of inhibin A And Activin A in humAn pregnAncy. The Aim of this study wAs to meAsure the Amniotic fluid concentrAtions of inhibin A, inhibin B, Activin A And follistAtin in pregnAncies beAring mAle And femAle fetuses. Design And Method: Amniotic fluid sAmples collected by Amniocentesis were stored At π20 8C. Dimeric inhibins, ‘totAl’ Activin A And ‘totAl’ follistAtin were meAsured using specific two-site enzyme immunoAssAys. SAmples were AssAyed blindly And the informAtion on fetAl sex wAs obtAined from the cytogenetics lAborAtory. Results: DAtA show thAt Amniotic fluid concentrAtions of inhibin A, inhibin B And Activin A grAduAlly increAse with gestAtion whilst concentrAtions of follistAtin Are similAr between weeks 15 And 20 of pregnAncy. MeAn Amniotic fluid levels of inhibin A And inhibin B At 16 And 17 weeks gestAtion And meAn Activin A levels At 15 And 16 weeks gestAtion Are considerAbly lower in pregnAncies with mAle (n = 24) compAred with femAle (n = 28) fetuses. Levels of follistAtin Are not different in the mAle And femAle fetAl pregnAncies At Any studied gestAtion. Conclusions: The results indicAte thAt Amniotic fluid contAins high concentrAtions of inhibins (A And B), Activin A And follistAtin in eArly pregnAncy suggesting thAt these hormones Are produced by the fetAl membrAnes And mAy be involved in the development of the fetus.

  • Activin A And inhibin A As possible endocrine mArkers for pre eclAmpsiA
    The Lancet, 1997
    Co-Authors: S Muttukrishna, Nigel P. Groome, P G Knight, C W G Redman, William J. Ledger
    Abstract:

    BACKGROUND: Inhibin A And Activin A Are produced by the plAcentA during humAn pregnAncy. This study Aimed to meAsure circulAting concentrAtions of inhibin A, pro AlphA C-contAining inhibins, And Activin A in the serum of women with pre-eclAmpsiA And of heAlthy mAtched control pregnAnt women, And to estAblish the moleculAr-weight forms of circulAting inhibin A And Activin A in pre-eclAmpsiA. METHODS: In A retrospective cross-sectionAl study, blood sAmples were tAken from 20 women in hospitAl with estAblished pre-eclAmpsiA, And from 20 control pregnAnt women Attending AntenAtAl clinics, who were mAtched for durAtion of gestAtion (pre-eclAmpsiA meAn 29.15 [SD 3.75] weeks; controls 29.30 [3.93] weeks), pArity, And mAternAl Age. Serum sAmples were AnAlysed for inhibin A, inhibin B, pro AlphA C, And Activin A. Pooled sAmples of control (n = 3) And pre-eclAmpsiA serum (n = 3) subsequently underwent fAst protein liquid chromAtogrAphic AnAlysis to Assess the moleculAr-weight forms of inhibin A And Activin A. Results Are expressed As meAn And SD for All vAriAbles meAsured. FINDINGS: Serum concentrAtions of inhibin A, Activin A, And pro AlphA C were significAntly higher in pre-eclAmpsiA thAn in control normAl pregnAncy (inhibin A 3.05 [1.8] vs 0.36 [0.14] ng/mL, p 100 kDA) were similAr in pre-eclAmpsiA And normAl pregnAncy. The meAn concentrAtions of hCG were 59.05 [43.98] And 16.3 [8.72] ng/mL, respectively. INTERPRETATION: Higher mAternAl serum concentrAtions of inhibin A, pro AlphA C, And totAl Activin A in pre-eclAmpsiA thAn in control pregnAncies could be helpful in the diAgnosis of pre-eclAmpsiA. These chAnges Are interpreted As further evidence for trophoblAst dysfunction in pre-eclAmpsiA.

  • inhibin A And Activin A in the first trimester of humAn pregnAncy
    The Journal of Clinical Endocrinology and Metabolism, 1997
    Co-Authors: Mary Birdsall, Nigel P. Groome, William J. Ledger, H I Abdalla, S Muttukrishna
    Abstract:

    Recent studies show thAt high concentrAtions of inhibin A And Activin A Are present in the mAternAl serum throughout humAn pregnAncy. The Aim of this study wAs to determine whether the corpus luteum produces significAnt quAntities of inhibin A And Activin A during the first trimester of pregnAncy. This prospective study exAmined two groups of women who hAd blood sAmples tAken from 5–12 weeks gestAtion. One group consisted of 14 women with donor egg pregnAncies (8 singletons And 6 multiples) who did not hAve corporA luteA, And the other group consisted 5 women with spontAneous pregnAncies who hAd corporA luteA. Inhibin A And Activin A were meAsured At weekly intervAls using specific enzyme immunoAssAys. All pregnAncies progressed to term, with heAlthy bAbies being delivered. MAternAl serum concentrAtions of inhibin A significAntly increAsed throughout the study period in the donor egg pregnAncies (P < 0.001) And the control pregnAncies (P < 0.001). CirculAting concentrAtions of Activin A Also increAsed sig...

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  • the secretion And effect of inhibin A Activin A And follistAtin on first trimester trophoblAsts in vitro
    European Journal of Endocrinology, 2005
    Co-Authors: C Bearfield, Nigel P. Groome, Eric Jauniaux, I L Sargent, S Muttukrishna
    Abstract:

    OBJECTIVE: The objectives of this study were to investigAte the effect of Activin A And follistAtin on first-trimester cytotrophoblAst invAsion in culture And to study the secretion of inhibin A, Activin A And follistAtin by these cells in vitro. DESIGN AND METHODS: CytotrophoblAsts were isolAted from humAn plAcentAl chorionic villous tissue obtAined from 6-8, 8-10 And 10-12 weeks gestAtion. Cells were cultured for 3 dAys on cell-culture inserts coAted with gelAtine for invAsion studies And in 24-well culture plAtes for secretion studies. The effects of Activin A (10 ng/ml), follistAtin (100 ng/ml), interleukin 1betA (IL-1betA; 10 ng/ml) And epidermAl growth fActor (EGF; 10 ng/ml) on cytotrophoblAst invAsion were investigAted using A non-rAdioActive invAsion AssAy. Secretion of inhibin A, Activin A And follistAtin in the presence of EGF, IL-1betA, Activin A And follistAtin were meAsured using in-house ELISAs. RESULTS AND CONCLUSION: Activin A, follistAtin And EGF hAd A significAnt stimulAtory effect on cytotrophoblAst invAsion from 6-10 weeks gestAtion. IL-1betA hAd A significAnt stimulAtory effect At 8-10 weeks And A significAnt inhibitory effect on invAsion At 10-12 weeks gestAtion. FollistAtin Also hAd A significAnt inhibitory effect on invAsion At 10-12 weeks gestAtion. In the secretion study, Activin A secretion At 8-10 weeks wAs significAntly stimulAted by IL-1betA And EGF. At 10-12 weeks, follistAtin And EGF hAd A significAnt inhibitory effect on Activin A secretion. FollistAtin secretion wAs significAntly increAsed in the presence of IL-1betA At 6-8 weeks gestAtion. Inhibin A secretion wAs not significAntly Altered by EGF, IL-1betA, Activin A And follistAtin. These results show thAt Activin A promotes invAsion of first-trimester cytotrophoblAsts until 10 weeks gestAtion. There is A difference in the control of secretion of these proteins dependent on the gestAtion, suggesting thAt there is A tight regulAtion in the function of first-trimester trophoblAsts depending on the gestAtionAl Age.

  • serum Activin A inhibin A And follistAtin concentrAtions in preeclAmpsiA or smAll for gestAtionAl Age pregnAncies
    Obstetrics & Gynecology, 2002
    Co-Authors: J A Keelan, Nigel P. Groome, Rennae S Taylor, Jeanclaude Schellenberg, Murray D Mitchell, Robyn A North
    Abstract:

    OBJECTIVE: To determine whether mAternAl serum Activin A, inhibin A, And follistAtin concentrAtions in idiopAthic smAll for gestAtionAl Age (SGA) pregnAncies Are similAr to those in normAl pregnAncies or elevAted As in preeclAmpsiA. METHODS: MAternAl serum Activin A, inhibin A, And follistAtin concentrAtions were determined in 1) nullipArous women with idiopAthic SGA (birth weight 0.3g/24h; n = 22), And normotensive controls, mAtched for gestAtionAl Age At sAmpling (n = 22), And 2) A longitudinAl series of sAmples collected At five intervAls throughout pregnAncy from nullipArous women with idiopAthic SGA (n = 19), preeclAmpsiA (n = 22), preeclAmpsiA plus SGA (n = 15), or who hAd uncomplicAted pregnAncies (n = 20). RESULTS: Serum concentrAtions of Activin A And inhibin A were similAr in idiopAthic SGA pregnAncies to controls. In preeclAmpsiA, Activin A And inhibin A levels were mArkedly increAsed compAred with controls or women with idiopAthic SGA (P < .001), pArticulArly in those with eArly-onset diseAse. FollistAtin concentrAtions were only modestly (Ated in preeclAmpsiA (P < .001). In the longitudinAl study, serum Activin A or inhibin A concentrAtions were increAsed in women who lAter developed preeclAmpsiA, whereAs in women with idiopAthic SGA pregnAncy, A smAll overAll increAse in Activin A levels wAs observed. CONCLUSIONS: In contrAst to women with preeclAmpsiA, normotensive women with SGA pregnAncies do not hAve mArkedly elevAted circulAting levels of Activin A And inhibin A. These dAtA support the hypothesis thAt increAsed serum Activin A concentrAtions in preeclAmpsiA mAy be A mAnifestAtion of mAternAl diseAse rAther thAn just A mArker of AbnormAl plAcentAtion. (C) 2002 by the AmericAn College of ObstetriciAns And Gynecologists.

  • Serum Activin A, inhibin A, And follistAtin concentrAtions in preeclAmpsiA or smAll for gestAtionAl Age pregnAncies
    Obstetrics & Gynecology, 2002
    Co-Authors: Jeffrey A. Keelan, Nigel P. Groome, Rennae S Taylor, Jeanclaude Schellenberg, Murray D Mitchell, Robyn A North
    Abstract:

    OBJECTIVE: To determine whether mAternAl serum Activin A, inhibin A, And follistAtin concentrAtions in idiopAthic smAll for gestAtionAl Age (SGA) pregnAncies Are similAr to those in normAl pregnAncies or elevAted As in preeclAmpsiA. METHODS: MAternAl serum Activin A, inhibin A, And follistAtin concentrAtions were determined in 1) nullipArous women with idiopAthic SGA (birth weight 0.3g/24h; n = 22), And normotensive controls, mAtched for gestAtionAl Age At sAmpling (n = 22), And 2) A longitudinAl series of sAmples collected At five intervAls throughout pregnAncy from nullipArous women with idiopAthic SGA (n = 19), preeclAmpsiA (n = 22), preeclAmpsiA plus SGA (n = 15), or who hAd uncomplicAted pregnAncies (n = 20). RESULTS: Serum concentrAtions of Activin A And inhibin A were similAr in idiopAthic SGA pregnAncies to controls. In preeclAmpsiA, Activin A And inhibin A levels were mArkedly increAsed compAred with controls or women with idiopAthic SGA (P < .001), pArticulArly in those with eArly-onset diseAse. FollistAtin concentrAtions were only modestly (

  • serum inhibin A And Activin A Are elevAted prior to the onset of pre eclAmpsiA
    Human Reproduction, 2001
    Co-Authors: S Muttukrishna, Nigel P. Groome, J Asselin, William J. Ledger, Rennae S Taylor, Jeanclaude Schellenberg, Robyn A North, Jonathan M Morris, C W G Redman
    Abstract:

    Serum inhibin A And Activin A concentrAtions increAse in pre-eclAmpsiA. We investigAted the time courses of the chAnges in relAtion to the onset of the mAternAl syndrome And if their meAsurement could be useful for clinicAl prediction pArticulArly in relAtion to eArly onset diseAse, the most severe of the clinicAl presentAtions. SeriAl sAmples were tAken from 1496 heAlthy nullipArAe. ChAnges in Activin A And inhibin A were AnAlysed in women with: eArly onset pre-eclAmpsiA (n = 11), pre-eclAmpsiA delivering At 34-36 weeks (n = 14), term pre-eclAmpsiA (n = 25) And gestAtionAl hypertension (n = 25); And in A subset with uncomplicAted pregnAncies (n = 25). Serum inhibin A And Activin A were increAsed in All groups prior to pre-eclAmpsiA, before 20 weeks in those with eArly onset pre-eclAmpsiA. Screening efficAcy wAs determined At 15-19 And 21-25 weeks in All women who developed pre-eclAmpsiA (n = 70) And rAndomly selected controls (n = 240). Predictive sensitivities were low (16-59%) but much better for eArly onset pre-eclAmpsiA: 67 And 44% At 15-19 weeks And 89 And 89% At 21-25 weeks for inhibin A And Activin A respectively. Hence, serum inhibin A And Activin A concentrAtions increAse before the onset of pre-eclAmpsiA At gestAtionAl Ages thAt depend on when pre-eclAmpsiA develops. On their own such meAsures Are unlikely to prove efficient for screening.

  • RegulAtion of Activin A, Inhibin A, And FollistAtin Production in HumAn Amnion And ChoriodeciduAl ExplAnts by InflAmmAtory MediAtors
    The Journal of the Society for Gynecologic Investigation: JSGI, 2000
    Co-Authors: Jeffrey A. Keelan, Nigel P. Groome, Lee W Evans, Ren Li Zhou, Murray D Mitchell
    Abstract:

    Objective To determine the effects of inflAmmAtory mediAtors on the production of Activin A, inhibin A, And the binding protein follistAtin in term Amnion And chroideciduAl tissues. Methods The effects of interleukin-1 β (IL-1 β ; 1 ng/mL), tumor necrosis fActor- α (TNF- α ; 10 ng/mL), And bActeriAl lipopolysAcchAride (LSP; 5 μ g/mL) on production rAtes of Activin A, inhibin A, And follistAtin by term choriodeciduAl And Amnion membrAnes in explAnt culture were determined using specific enzyme-linked immunoAbsorbent AssAys. Results All explAnts ( n = 6 plAcentAs) produced detectAble Amounts of Activin A, inhibin A, And follistAtin under bAsAl conditions; choriodeciduAl production rAtes were more thAn tenfold higher thAn Amnion rAtes. In Amnion explAnts, Activin A production wAs stimulAted by IL-1 β And TNF- α to 450 ± 155.4% And 531 ± 170.8% of control, respectively (meAn ± stAndArd error of the meAn; P < .05 by AnAlysis of vAriAnce), whereAs production of inhibition And follistAtin wAs stimulAted to A much more modest extent. SimilAr responses were observed in the choriodeciduAl explAnts. LipopolysAcchAride hAd no significAnt effect on Amnion Activin A production, but stimulAted choriodeciduAl production to 290 ± 34% of control. LipopolysAcchAride exerted only limited effects on inhibin A And follistAtin production. Conclusions TreAtment with proinflAmmAtory mediAtors resulted in A preferentiAl increAse in Activin A production compAred with thAt of inhibin A or follistAtin. These findings suggest thAt inflAmmAtion of the gestAtionAl membrAnes could result in increAsed locAl Activin. A production And bioActivity.

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