Endotoxin exposure and puberty in female rats: the role of nitric oxide and caspase-1 inhibition in neonates

Bacterial toxins are widespread in the environment as well as in the digestive system of humans and animals. Toxin from Gram-negative bacteria (endotoxin or lipopolysaccharide; LPS) has a life-long programming effect on reproduction in rats, but the mediators have not been well-documented, so we investigated the effects of LPS on the timing of puberty in female rats. Because the levels of nitric oxide (NO) and interleukin 1β (IL-10) increase following injection of LPS, we injected neonates (post-natal day (pnd) 7) with LPS, with or without NO or IL-1β inhibitors. Half of the prepubescent (pnd 30) animals received an additional LPS injection. Vaginal opening, number of ovarian follicles, and serum anti-LPS antibodies were determined. A single LPS injection was sufficient to reduce the primordial follicle pool, but puberty was delayed when rats received 2 LPS injections (at pnd 7 and 30). NO or IL-1β inhibitors improved both of these parameters, suggesting that the early detrimental effects of LPS on puberty and primordial follicle pool are mediated by NO and IL-1β. Key words: lipopolysaccharide, puberty, ovarian function, IL-1β, nitric oxide, female rats. Les toxines bacteriennes sont repandues dans l'environnement et dans le systeme digestif des humains et des animaux. On sait que la toxine des bacteries negatives a Gram (endotoxine ou lipopolysaccharide; LPS) exerce un effet de programmation sur la reproduction des rats qui dure toute la vie, mais ses mediateurs ne sont pas bien documentes. Puisque les niveaux d'oxyde nitrique (NO) et d'interleukine 1β (IL-10) augmentent a la suite d'une injection de LPS, les auteurs ont examine les effets d'une injection neonatale de LPS (jour 7 postnatal) en presence ou non d'inhibiteurs de NO ou d'IL-1β, sur la maturation pubertaire de rats femelles. La moitie des animaux a recu une injection supplementaire de LPS en periode pre-pubertaire (jour 30 postnatal). L'ouverture vaginale, le nombre de follicules ovariens et la presence d'anticorps anti-LPS dans le serum ont ete determines. Une injection unique de LPS suffisait a reduire le pool de follicules primordiaux mais la puberte n'etait retardee que chez les rates ayant recu deux injections de LPS, aux jours 7 et 30 postnataux. Les inhibiteurs amelioraient les deux parametres, suggerant que les effets nocifs precoces du LPS sur la puberte et le pool de follicules primordiaux passent par l'intermediaire du NO et de l'IL-1β. [Traduit par la Redaction] Mots-cles: lipopolysaccharide, puberte, fonction ovarienne, IL-1β, oxyde nitrique, rats femelles.
Introduction The environmental chemicals that have an impact on human health are not only man-made or man-introduced agents (Rylander 2002); humans are continuously exposed to toxins originating from microorganism-associated molecular [...]