PMID- 23077169 OWN - NLM STAT- MEDLINE DCOM- 20130514 LR - 20151119 IS - 1529-7268 (Electronic) IS - 0006-3363 (Linking) VI - 87 IP - 6 DP - 2012 Jun TI - Hepatocyte growth factor is a mouse fetal Leydig cell terminal differentiation factor. PG - 146 LID - 10.1095/biolreprod.112.104638 [doi] AB - The hepatocyte growth factor (HGF) is a pleiotropic cytokine and a well-known regulator of mouse embryonic organogenesis. In previous papers, we have shown the expression pattern of HGF and its receptor, C-MET, during the different stages of testis prenatal development. We demonstrated that C-MET is expressed in fetal Leydig cells (FLCs) and that HGF stimulates testosterone secretion in organ culture of late fetal testes. In the present study, we analyzed the proliferation rate, apoptotic index, and differentiation of FLCs in testicular organ culture of 17.5 days postcoitum (17.5 dpc) embryos to clarify the physiological role of HGF in late testis organogenesis. Based on our data, we conclude the following: 1) HGF acts as an antiapoptotic factor that is able to reduce the number of apoptotic FLCs and testicular caspase-3 active fragment; 2) HGF does not affect FLC proliferation; 3) HGF significantly increases expression of insulin-like 3 (INSL3), a marker of Leydig cell terminal differentiation, without affecting 3beta-hydroxysteroid dehydrogenase (3betaHSD) expression; 4) HGF significantly decreases the expression of nestin, a marker of Leydig cell progenitors; and 5) HGF significantly increases the number of fully developed FLCs. Taken together, these observations demonstrate that HGF is able to act in vitro as a survival and differentiation factor in FLC population. FAU - Ricci, Giulia AU - Ricci G AD - Department of Experimental Medicine, Histology and Embryology Laboratory, School of Medicine, Second University of Naples, Naples, Italy. giulia.ricci@unina2.it FAU - Guglielmo, Maria Cristina AU - Guglielmo MC FAU - Caruso, Maria AU - Caruso M FAU - Ferranti, Francesca AU - Ferranti F FAU - Canipari, Rita AU - Canipari R FAU - Galdieri, Michela AU - Galdieri M FAU - Catizone, Angela AU - Catizone A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121221 PL - United States TA - Biol Reprod JT - Biology of reproduction JID - 0207224 RN - 0 (Biomarkers) RN - 0 (HGF protein, mouse) RN - 0 (Intermediate Filament Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Nes protein, mouse) RN - 0 (Nestin) RN - 0 (Peptide Fragments) RN - 0 (RNA, Messenger) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - EC 3.4.22.- (Casp3 protein, mouse) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Animals MH - Apoptosis MH - Biomarkers/metabolism MH - Caspase 3/metabolism MH - *Cell Differentiation MH - Cell Proliferation MH - Cell Survival MH - Hepatocyte Growth Factor/genetics/*metabolism MH - Intermediate Filament Proteins/metabolism MH - Leydig Cells/*cytology/enzymology/metabolism MH - Male MH - Mice MH - Mice, Inbred Strains MH - Nerve Tissue Proteins/metabolism MH - Nestin MH - Organ Culture Techniques MH - *Organogenesis MH - Peptide Fragments/metabolism MH - Proto-Oncogene Proteins c-met/genetics/*metabolism MH - RNA, Messenger/metabolism MH - *Signal Transduction MH - Testis/cytology/*embryology/metabolism EDAT- 2012/10/19 06:00 MHDA- 2013/05/15 06:00 CRDT- 2012/10/19 06:00 PHST- 2012/10/19 06:00 [entrez] PHST- 2012/10/19 06:00 [pubmed] PHST- 2013/05/15 06:00 [medline] AID - biolreprod.112.104638 [pii] AID - 10.1095/biolreprod.112.104638 [doi] PST - epublish SO - Biol Reprod. 2012 Dec 21;87(6):146. doi: 10.1095/biolreprod.112.104638. Print 2012 Jun.