Neonatal LPS admınıstratıon and long-term programmıng of reproductıon: The role of NOS and Caspase-1 ınhıbıtıons

In this thesis, long-term programming effect of neonatally injected bacterial endotoxin lipopolysaccharide (LPS) on reproduction was assessed in female rats. Additionally, in order to estabilish the roles of mediators of LPS action, inhibitors of NOS (L-NAME) and caspase-1 inhibitor (Q-Vd-OPh) were injected together with LPS. For that purpose, on postnatal day 7, female pups were injected once with either saline (control), LPS(50µg/kg), LPS(50µg/kg)+ L-NAME (40mg/kg) or LPS(50µg/kg)+ Q-Vd-OPh (1mg/kg). On postnatal day 30, these rats were either injected with saline or LPS (50 µg/kg) to observe effects of prepubertal stress on timing of puberty (as vaginal opening), estrus cyclicity (by smear test), cytokine production (e.g. IL-1ß and TNF-?), folliculogenesis and on Escherichia coli spesific anti-LPS antibody levels. Approximately on day 75, right ovary and blood samples were taken under terminal anaesthesia and the experiment was ended.Puberty was delayed in rats receiving double LPS injections but was not affected in those which also received NOS and IL-1ß inhibitors. Although LPS injections reduced the size of primordial follicular pool, NOS inhibitor, but not IL-1ß intibitor, prevented this reduction. Groups receiving both LPS injections had higher anti-LPS spesific antibody response. Serum NO levels were found to be similar among all groups. Serum IL-1ß and TNF-? concentrations were found to be undetectably low.In conclusion, it has been found out (1) that LPS injections programms reproduction by delaying puberty, by reducing the number of primordial follicles in the ovary and by increasing the level of anti-LPS spesific antibodies in the blood and (2) that NO and IL-1 ß plays a crucial role in this programming.