Decidual Activin: Its Role In the Apoptotic Process and Its Regulation by Prolactin1

• Published in: Biology of reproduction 2003-05, Vol.68 (5), p.1687-1694
• Main Authors: Tessier, Christian, Prigent-Tessier, Anne, Bao, Lei, Telleria, Carlos M, Ferguson-Gottschall, Susan, Gibori, Gil B, Gu, Yan, Bowen-Shauver, Jennifer M, Horseman, Nelson D, Gibori, Geula
• Format: Article
• Language: English
• Subjects: activin; apoptosis; Contents; decidua; prolactin
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.102.011684

Successful pregnancy requires profound differentiation and reorganization of the uterine tissues including, as pregnancy progresses, extensive apoptosis of decidual tissue to accommodate the developing conceptus. We have previously shown a positive correlation between expression of activin A and apoptosis in the decidua and have also shown that expression of activin A occurs at the time when prolactin (PRL) receptors disappear from decidual cells. The goals of this study were to examine whether activin A plays a role in decidual apoptosis and whether expression of activin A in the decidua is regulated by PRL and placental lactogens. Studies were carried out using primary rat decidual cells, a decidual cell line (GG-AD), and PRL null mice. Treatment of decidual cells with activin A significantly increased DNA degradation, caspase 3 activity, and caspase 3 mRNA expression. However, this effect was observed only in the absence of endogenous activin production by these cells. Addition of follistatin to decidual cells that were producing activin A decreased both caspase 3 activity and mRNA expression. Similarly, addition of activin-blocking antibodies to cultures of GG-AD cells, which also produce activin A, caused a reduction in both DNA degradation and caspase 3 activity. PRL and placental lactogens caused an inhibition of activin A mRNA expression in primary decidual cells. Even more convincingly, decidua of PRL null mice expressed abundant activin A at a time when no expression of this hormone is detected in wild-type mice and treatment of PRL null mice with PRL caused a profound inhibition of activin A mRNA expression. In summary, our investigations into the role and regulation of decidual activin have revealed that activin A can induce cell death in the decidua and that its expression is under tight regulation by PRL and placental lactogens.