title: Concanavalin-A induces granulosa cell death and inhibits FSH-mediated follicular growth and ovarian maturation in female rats.
abstract: Reproductive success stems from a finely regulated balance between follicular maturation and atresia, in which the role of carbohydrate structure is poorly understood. Here, we describe for the first time a fraction of purified recombinant human FSH that is capable of bringing about the cell death of granulosa cells and preventing follicular maturation in a rat model. Further analysis by mass spectrometry revealed the presence of the lectin Concanavalin-A (Con-A) within this fraction of recombinant FSH. Using both the fractionated FSH and Con-A, the observed cell death was predominantly located to the granulosa cells. Ex vivo culture of rat follicles demonstrated that follicle degeneration occurred and resulted in the release of a denuded and deteriorated oocyte. Moreover, in vivo experiments confirmed an increase in atresia and a corresponding reduction confined to follicle in early antral stage. As a mechanism of action, Con-A reduces ovarian proliferation, Von Willebrand staining, and angiogenesis. Based on the observation that Con-A may induce granulosa cell death followed by follicle death, our results further demonstrate that follicular carbohydrate moiety is changing under the influence of FSH, which may allow a carbohydrate-binding lectin to increase granulosa cell death. The physiological consequences of circulating lectin-like molecules remain to be determined. However, our results suggest a potential exploitation of carbohydrate binding in fertility and ovarian cancer treatment. This work may shed light on a key role of carbohydrates in the still obscure physiological process of follicular selection and atresia.
authors.affiliation: Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile. evelasquez@bio.puc.cl
authors.forename: Ethel V
authors.initials: EV
authors.lastname: Velasquez
authors.forename: Mariana
authors.initials: M
authors.lastname: Ríos
authors.forename: María Elena
authors.initials: ME
authors.lastname: Ortiz
authors.forename: Carlos
authors.initials: C
authors.lastname: Lizama
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Nuñez
authors.forename: Dalhia
authors.initials: D
authors.lastname: Abramovich
authors.forename: Felipe
authors.initials: F
authors.lastname: Orge
authors.forename: Barbara
authors.initials: B
authors.lastname: Oliva
authors.forename: Renán
authors.initials: R
authors.lastname: Orellana
authors.forename: Manuel
authors.initials: M
authors.lastname: Villalon
authors.forename: Ricardo D
authors.initials: RD
authors.lastname: Moreno
authors.forename: Marta
authors.initials: M
authors.lastname: Tesone
authors.forename: Anne
authors.initials: A
authors.lastname: Rokka
authors.forename: Garry
authors.initials: G
authors.lastname: Corthals
authors.forename: Horacio B
authors.initials: HB
authors.lastname: Croxatto
authors.forename: Fernanda
authors.initials: F
authors.lastname: Parborell
authors.forename: Gareth I
authors.initials: GI
authors.lastname: Owen
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects* / Q000502:physiology; D008934:Mitogens / Q000494:pharmacology; D006080:Ovarian Follicle / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D010053:Ovary / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation / Q000187:drug effects*
chemical_list: D008934:Mitogens; D003208:Concanavalin A; D005640:Follicle Stimulating Hormone