The medial preoptic area of the adult sheep contains an ovine sexually dimorphic nucleus (oSDN) that is larger and has more neurons in males than in females. lamb fetus decreased during the last half of the 147-day gestation. The ratio of bcl-2/bax gene expression was highest at gestational day 85 but was equivalent between males and females. TUNEL staining in the MPNc was very low and although it decreased significantly with age it was not significantly different between sexes. These results using two different methods to assess cell death indicate that a sex difference in the incidence of cell death is not a primary mechanism leading to sexual differentiation of the oSDN. time course for elimination of apoptotic cells has been estimated to take about 72 h (Hu Yuri Ozawa Lu and Kawata 1997 so it is possible that our sampling schedule is insufficiently comprehensive to capture the critical period for apoptosis in females. It is also possible that sex differences in the incidence of Dienestrol cell death are regionally localized Dienestrol within the nucleus or exist within the migratory pathway for cells that populate it either of which would have been missed by the limits of the sampling procedure employed. For these reasons the current study cannot totally exclude the possibility that the modulation of cell death plays some role in the sexual differentiation of the oSDN. Thus future studies using more frequent sampling should be performed to fully assess the degree to which apoptosis is involved in oSDN formation. Other possible mechanisms for generating sex-related brain volume differences include: differential neurogenesis cell migration or differentiation of phenotype (Forger 2006 Neurons comprising the SDN-POA of rats originate from the subependymal lining of the 3 ventricle (Jacobson Davis and Gorski 1985 Studies that examined birthdate of SDN-POA neurons found similar numbers generated prenatally in male and female rats (Jacobson Davis and Gorski 1985 Kondo Usui and Sakuma 2010 Studies in rats and mice support the idea that migration plays a major role in the establishment of the SDN-POA (Hamada and Sakuma 2010 Kondo and Sakuma 2007 and Sakuma 2010 Migration into the SDN-POA is faster in male than in female mice suggesting a way that more cells could reach their final destination in males than in females and ultimately generate a larger nucleus (Tobet Knoll Hartshorn Aurand Stratton Kumar Searcy and McClellan 2009 Recent evidence indicates that stem cell activity in the rostral end of the 3rd ventricle may continue to play a role in the postnatal development and structural maintenance of the SDN-POA in rats (He Ferguson Cui Greenfield and Paule 2013 In ferrets a species like sheep in that a sexually dimorphic medial preoptic nucleus develops prior to birth (Cherry Basham Weaver Krohmer and Baum 1990 Park et al. (Park Baum Paredes and Tobet 1996 Tobet and Baum 1998 found no sex difference in neurogenesis migration or cell death and concluded that the specification of a distinctive neuronal phenotype i.e. soma size area of dendritic fields or capacity to produce a specific molecule may be responsible for establishing volumetric sex differences in brain. The role of cell death and migration has also been challenged by recent studies in mice (Gilmore Varnum and Forger 2012 which show that blocking bax-dependent developmental cell death through targeted deletion of the bax gene does not prevent sex differences from developing in the number of calbindin-immunoreactive neurons in the SDN. Mice overexpressing bcl-2 or carrying null mutation for bax also retained sex differences in the number of vasopressin and calbindin neurons in the bed n. of the stria terminalis and kisspeptin in the anteroventral periventricular preoptic nucleus while overall number of neurons expressing these neuropeptides was unchanged (De Vries Jardon Reza Rosen Immerman and Forger 2008 Varnum and Forger Dienestrol 2012 Murray Poling Dhamija Forger and Kauffman 2010 Together these studies suggest that the differentiation of cellular phenotypes may be a more likely mechanism for establishing brain sex differences than hormonal regulation of cell death. In summary we propose that Rabbit polyclonal to ACTN4. the volumetric sex difference found in the sheep MPNc may not rely Dienestrol on differences in the incidence cell death but may instead be the result of testosterone’s action on the differentiation of neuronal phenotype. The sheep model has not been as extensively studied as rodents and ferrets. However by extrapolating from these other models it seems unlikely that prenatal testosterone controls neurogenesis or migration to produce the.