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Endometrial Expression and Secretion of Activin A, But Not Follistatin, Increase in the Secretory Phase of the Menstrual Cycle

Filiberto M. Severi, MD

Stefano Luisi, MD

Pasquapina Ciarmela

Giulia Calonaci, MD

Luigi Cobellis, MD, PhD

Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy

Felice Petraglia, MD

Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Policlinico "Le Scotte," Viale Bracci, 53100 Siena, Italy petraglia{at}unisi.it

Objective: Activin A is a growth factor expressed by human endometrium, and its biologic effects are counteracted by follistatin. We evaluate whether activin A and follistatin 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 immunohistochemistry (IHC), respectively. Activin A and follistatin 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 and follistatin 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 ßA but not in follistatin was observed in glandular epithelium during the secretory phase. Activin A but not follistatin 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 was found between activin A, but not follistatin, and menstrual cycle days (P < .0001) or endometrial thickness (P < .0001).

Conclusion: Both activin A and follistatin mRNAs are expressed by human endometrium; however, activin A but not follistatin peptide expression and secretion were increased in the secretory phase of the menstrual cycle, suggesting an important role in human endometrium.

Key Words: Inhibin • follicular phase • luteal phase • ultrasound • endometrial thickness

Journal of the Society for Gynecologic Investigation, Vol. 10, No. 4, 237-243 (2003)
DOI: 10.1016/S1071-55760300045-5


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