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.

Metabolic signatures in human follicular fluid identify lysophosphatidylcholine as a predictor of follicular development

“…In rats, FSH alters follicular carbohydrate moiety, which, in turn, promotes carbohydrate-lectin association, which increases granulosa cell death. Based on these evidences, carbohydrate is critical for follicular selection and atresia 17 . Studies revealed that metabolism in porcine atresia follicles is characterized by reduced lipids (particularly, phospholipids) content and elevated amino and bile acids.…”

Concanavalin A promotes angiogenesis and proliferation in endothelial cells through the Akt/ERK/Cyclin D1 axis

“… 2011 ; Velasquez et al. 2013 ). A specific concentration of Con A initiated apoptosis through cross-linking of Con A receptors on cortical neurons (Kulkarni and McCulloch 1995 ).…”

Effects of jacalin and follicle-stimulating hormone onin vitrogoat primordial follicle activation, survival and gene expression

“…Recently, several lectins have been speculated to possess pro-apoptotic, pro-autophagic, and anti-angiogenic properties in cancer cell lines (Fu et al ., 2011; Li et al ., 2011). In this context, Velasquez et al ., (2013) demonstrated that the lectin concanavalin A (Con A) inhibited the stimulatory effect of FSH and induces oocyte degeneration and death of rat granulosa cells. On the other hand, addition of 10 mg/ml phytohemagglutinin (PHA) during in vitro culture caprine secondary follicles stimulated antrum formation and expression of FSH-R and PCNA mRNAs, which helped to keep ultrastructural integrity of cultured follicles (Cunha et al ., 2013).…”