Concanavalin-A Induces Granulosa Cell Death and Inhibits FSH-Mediated Follicular Growth and Ovarian Maturation in Female Rats

Velasquez EV; Rios M.; Ortiz ME; Lizama C.; Núñez E.; Abramovich, D; Orge, F; Oliva, B.; Orellana, R; Villalón M.; Moreno, RD; Tesone, M; Rokka, A; Corthals, G; Croxatto HB; et. al.

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. (Endocrinology 154: 1885-1896, 2013)

Más información

Título según WOS: Concanavalin-A Induces Granulosa Cell Death and Inhibits FSH-Mediated Follicular Growth and Ovarian Maturation in Female Rats
Título según SCOPUS: Concanavalin-A induces granulosa cell death and inhibits fsh-mediated follicular growth and ovarian maturation in female rats
Título de la Revista: ENDOCRINOLOGY
Volumen: 154
Número: 5
Editorial: ENDOCRINE SOC
Fecha de publicación: 2013
Página de inicio: 1885
Página final: 1896
Idioma: English
URL: http://press.endocrine.org/doi/abs/10.1210/en.2012-1945
DOI:

10.1210/en.2012-1945

Notas: ISI, SCOPUS