title: Stereological assessment of sexual dimorphism in the rat liver reveals differences in hepatocytes and Kupffer cells but not hepatic stellate cells.
abstract: There is long-standing evidence that male and female rat livers differ in enzyme activity. More recently, differences in gene expression profiling have also been found to exist; however, it is still unclear whether there is morphological expression of male/female differences in the normal liver. Such differences could help to explain features seen at the pathological level, such as the greater regenerative potential generally attributed to the female liver. In this paper, hepatocytes (HEP), Kupffer cells (KC) and hepatic stellate cells (HSC) of male and female rats were examined to investigate hypothesised differences in number, volume and spatial co-localisation of these cell types. Immunohistochemistry and design-based stereology were used to estimate total numbers, numbers per gram and mean cell volumes. The position of HSC within lobules (periportal vs. centrilobular) and their spatial proximity to KC was also assessed. In addition, flow cytometry was used to investigate the liver ploidy. In the case of HEP and KC, differences in the measured cell parameters were observed between male and female specimens; however, no such differences were detected for HSC. Female samples contained a higher number of HEP per gram, with more binucleate cells. The HEP nuclei were smaller in females, which was coincident with more abundant diploid particles in these animals. The female liver also had a greater number of KC per gram, with a lower percentage of KC in the vicinity of HSC compared with males. In this study, we document hitherto unknown morphological sexual dimorphism in the rat liver, namely in HEP and KC. These differences may account for the higher regenerative potential of the female liver and lend weight to the argument for considering the rat liver as a sexually dimorphic organ.
authors.affiliation: Laboratory of Histology and Embryology, Department of Microscopy, ICBAS - Institute of Biomedical Sciences Abel Salazar, U.Porto - University of Porto, Porto, Portugal.|Histomorphology, Physiopathology and Applied Toxicology Group, CIIMAR - Interdisciplinary Centre of Marine and Environmental Research, U.Porto - University of Porto, Porto, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Marcos
authors.affiliation: Laboratory of Histology and Embryology, Department of Microscopy, ICBAS - Institute of Biomedical Sciences Abel Salazar, U.Porto - University of Porto, Porto, Portugal.|Histomorphology, Physiopathology and Applied Toxicology Group, CIIMAR - Interdisciplinary Centre of Marine and Environmental Research, U.Porto - University of Porto, Porto, Portugal.
authors.forename: Célia
authors.initials: C
authors.lastname: Lopes
authors.affiliation: Laboratory of Histology and Embryology, Department of Microscopy, ICBAS - Institute of Biomedical Sciences Abel Salazar, U.Porto - University of Porto, Porto, Portugal.|Histomorphology, Physiopathology and Applied Toxicology Group, CIIMAR - Interdisciplinary Centre of Marine and Environmental Research, U.Porto - University of Porto, Porto, Portugal.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Malhão
authors.affiliation: Scotland's Rural College, Epidemiology Research Unit - Future Farming Systems Group, Inverness, UK.
authors.forename: Carla
authors.initials: C
authors.lastname: Correia-Gomes
authors.affiliation: Laboratory of Cytometry, Department of Hematology, UMIB - Unit for Multidisciplinary Research in Biomedicine, CHP - Centro Hospitalar do Porto, ICBAS - Institute of Biomedical Sciences Abel Salazar, HSA - Hospital de Santo António, U.Porto - University of Porto, Porto, Portugal.
authors.forename: Sónia
authors.initials: S
authors.lastname: Fonseca
authors.affiliation: Laboratory of Cytometry, Department of Hematology, UMIB - Unit for Multidisciplinary Research in Biomedicine, CHP - Centro Hospitalar do Porto, ICBAS - Institute of Biomedical Sciences Abel Salazar, HSA - Hospital de Santo António, U.Porto - University of Porto, Porto, Portugal.
authors.forename: Margarida
authors.initials: M
authors.lastname: Lima
authors.affiliation: Institute of Biochemistry, Faculty of Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Gebhardt
authors.affiliation: Laboratory of Histology and Embryology, Department of Microscopy, ICBAS - Institute of Biomedical Sciences Abel Salazar, U.Porto - University of Porto, Porto, Portugal.|Histomorphology, Physiopathology and Applied Toxicology Group, CIIMAR - Interdisciplinary Centre of Marine and Environmental Research, U.Porto - University of Porto, Porto, Portugal.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Rocha
mesh_terms: D000818:Animals; D005260:Female; D005434:Flow Cytometry; D055166:Hepatic Stellate Cells; D022781:Hepatocytes; D007728:Kupffer Cells; D008099:Liver / Q000166:cytology*; D008297:Male; D017208:Rats, Wistar; D012727:Sex Characteristics
keywords: Kupffer cells; dimorphism; hepatic stellate cells; hepatocytes; liver; stereology