Second trimester levels of maternal serum total activin A and placental inhibin/activin a and bA subunit messenger ribonucleic acids in Down syndrome pregnancy Geralyn M Lambert-Messerlian, Stefano Luisi 1 , Pasquale Florio 1 , Vincenzo Mazza 2 , Jacob A Canick and Felice Petraglia 3 Department of Pathology and Laboratory Medicine, Brown University School of Medicine, Women and Infants Hospital, 101 Dudley Street, Providence, Rhode Island 02905, USA, 1 Department of Obstetrics and Gynecology, University of Pisa, 56100, Italy, 2 Department of Gynecology, Obstetrics and Pediatric Sciences, University of Modena, 41100, Italy and 3 Department of Surgical Sciences, Chair of Obstetrics and Gynecology, University of Udine, Udine, Italy (Correspondence should be addressed to G Lambert-Messerlian) Abstract Objectives: Previous data have shown that inhibin A (a/bA) is increased about twofold in maternal serum samples from Down syndrome pregnancy. Our objectives were to determine whether activin A (bA/bA) 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 a and bA 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 ¼ 0.36, Mann–Whitney U analysis) from those in unaffected pregnancies. The inhibin a subunit/GAPDH mRNA ratio, but not that of bA 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 a, but not bA, subunit. European Journal of Endocrinology 138 425–429 Introduction Down syndrome, trisomy 21, is the leading cause of severe mental retardation in industrialized countries. During the second trimester of pregnancy, fetal Down syndrome is associated with increased maternal serum levels of a variety of secretory products of the placenta, including progesterone, human placental lactogen, schwangerschaftsprotein 1, human chorionic gonado- tropin (hCG), and the free a and b subunits of hCG (1). hCG and free b-hCG are now commonly used in screening serum for fetal Down syndrome and their levels in Down syndrome are, on average, about double those in unaffected pregnancies (2). Recently, the amounts of another placental protein, inhibin A were also shown to be about twice as great in maternal serum from Down syndrome than in serum from unaffected pregnancies (3–8). This increase in serum inhibin A is important clinically: inhibin A increases the prenatal detection of Down syndrome by 7–22% when used as a serum marker in conjunction with hCG and alpha fetoprotein, with or without unconjugated estriol (uE3). Inhibin A is a dimeric protein consisting of an a and a bA subunit. In addition to the inhibin A heterodimer, free a subunits (8, 9) and a bA subunit homodimer (10–12), called activin A, circulate in maternal serum. As activin A is another placental protein (12) with a putative role in fetal development, an objective of the present study was to determine whether activin A was also increased in maternal serum of pregnancies affected with fetal Down syndrome. The mechanisms leading to increased inhibin A in Down syndrome are unknown, but could include increased gene expression of one or both subunits, increased protein translation or a lower rate of protein degradation. Each inhibin subunit is translated from a separate gene (13), but as is true of other placental European Journal of Endocrinology (1998) 138 425–429 ISSN 0804-4643  1998 Society of the European Journal of Endocrinology