GOTTARDO MarÍa Florencia
congresos y reuniones científicas
Mitochondrial-derived humanin peptides: New cytoprotective factors for ovarian cells?
MARVALDI CAROLINA; MARTIN DANIEL; GOTTARDO MF; PIDRE MATIAS; IMSEN M; ROMANOWSKI VICTOR; SEILICOVICH, ADRIANA; JAITA, GABRIELA
Congreso; 50th Annual Meeting of the Society for the Study of Reproduction; 2017
Along folliculogenesis, the fate of each follicle is controlled not only by endocrine but also by several paracrinefactors. Humanin (HN) and Rattin (rHN, rat homologous peptide) have cytoprotective action in several cell typessuch as neurons, spermatogonias and Leydig cells. Also, it was reported that HN could be secreted from cells. In theovary, HN mRNA was shown to be expressed in luteal cells. However, protein expression of HN peptides and theiraction in the ovary have not been described yet. We aimed to explore the expression and function of HN peptides inthe ovary from prepuberal rats, cycling adult rats and in a human granulosa-like tumor cell line (KGN). Weinvestigated the expression of rHN in ovarian sections from untreated prepuberal rats (rich in preantral follicles), ortreated either with DES (rich in early antral follicles) or PMSG (rich in preovulatory follicles). Immunohistochemical(IHC) staining showed rHN expression in granulose and theca cells, and also in oocytes. In PMSG-treated rats, rHNwas mainly expressed in theca cells. In ovarian sections from cycling rats the pattern of rHN expression was similarto that of treated prepuberal rats but rHN was also expressed in luteal cells. In addition, KGN cells expressed HN.Also, we analyzed the effect of HN on the viability of KGN cells by MTT assay. HN increased the viability of KGNcells (C: 0.24 ± 0.02, HN 0.25 µM: 0.40 ± 0.02, HN 0.5 µM: 0.36 ± 0.02, HN 1µM: 0.41 ± 0.01, means ± SEM ofquintuplicate samples from one experiment representative of two. p < 0.01 vs control. ANOVA). In addition, westudied the effect of endogenous HN inhibition using a shRNA plasmid on the apoptosis of KGN cells. HNr shRNAplasmid increased the percentage of apoptotic cells (plcontrol: 42%; plshRNA: 81%. p < 0.01, n=750-800, 2).Our results show that HNr is present in all follicular cells, including oocytes and luteal cells. Considering that theinhibition of endogenous HN increases the apoptosis and exogenous HN increases the viability of KGN cells, ourresults suggest that HN peptides may play a cytoprotective role in ovarian cells.