Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2012) 29 P1034

ICEECE2012 Poster Presentations Male Reproduction (63 abstracts)

G protein-coupled estrogen receptor 1- and estrogen receptor α-dependent pathways regulate spermatocytes apoptosis

A. Chimento , R. Sirianni , I. Casaburi , C. Ruggiero , M. Maggiolini , S. Andò & V. Pezzi


1University of Calabria, Rende, Italy.


In mammals, spontaneous apoptosis is observed particularly in differentiating spermatogonia and spermatocytes. We have previously demonstrated that 17β-estradiol (E2) in primary rat pachytene spermatocytes (PS) binds ESR1 and GPER1 to activate EGFR/ERK/c-Jun pathway leading to up regulation of bax, a pro-apoptotic factor. Aim of this study was to clarify the effector pathway(s) controlling spermatocytes apoptosis using as model GC-2 cells, an immortalized mouse pachytene spermatocytes cell line, reproducing primary cells responses to E2. Like in primary PS, ESR1 and GPER1 activation in GC-2 cells caused rapid ERK and c-Jun phosphorylation, bax up-regulation associated with apoptosis. We further demonstrated that apoptosis is induced by E2, as well as by specific ESR1 and GPER1 agonists, through sustained ERK, c-Jun and P38 phosphorylation, cytochrome c release, caspases 3 and endogenous substrate poly (ADP-ribose) polymerase (PARP) activation and increased expression of cell cycle inhibitor P21. When ESR1 or GPER1 expression were individually silenced, E2 was still able to decrease cell proliferation, only the concomitant silencing abolished E2 effect. These results indicate that GC-2 cells are a valid cell model to investigate the effects of E2 on spermatocytes apoptosis and show that E2, activating both ESR1 and GPER1, is able to induce an ERK1/2-, c-Jun- and P38-dependent mitochondrion apoptotic pathway in this type of cells. The definition of the molecular components of germ cells apoptosis will help us to better understand the consequences of the exposure to environmental estrogens, to provide new potential targets for the development of a non-androgen male contraceptive or for the development of novel therapeutic regimens to control germ cell tumors.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.

Volume 29

15th International & 14th European Congress of Endocrinology

European Society of Endocrinology 

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