Effect of LPS-induced inflammatory state on reproductive function in rabbit doe

Microbial infections, localized as well as systemic and the subsequent inflammation, are know to cause transitive or permanent infertility. Infectious agents as bacteria, fungi, viruses and parasites can impair human and animal reproduction. However, the mechanisms by which a status of infection/inflammation induce infertility are widely unknown. The objectives of this study were (1) to provide an adequate animal model of a systemic inflammatory status by intra-peritoneal injection of bacterial lipopolysaccharide (LPS) (2), to create a suitable animal model of sub-acute inflammation using local intra-cervical deposition of LPS and (3) to assess the effects of systemic and local inflammation on the uterine tissue and on the transport of spermatozoa in the genital tract of rabbit does. In experiment 1, 15 healthy New Zealand White rabbit does were divided into five homogeneous groups (n=3), receiving by intra-peritoneal injection 25, 50, 100 and 150 µg/kg body weight (b.w.) of E. coli LPS dissolved in 2 ml of sterile saline or only saline (control). White blood cells (WBC), rectal temperature and feed intake were observed for 3 consecutive days following the treatment. Inoculation of 100 µg/kg b.w. produces a reversible inflammation-like status that lasts for about 3 days, with minimal distress for the animals. The major symptoms were fever, anorexia, changes in WBC count and therefore it was used in other experiment. In experiment 2, ten New Zealand White does were divided in two groups (n=5) and inoculated close to the cervix region with 500 µg of E. coli LPS diluted in 2 ml of saline or only saline (control). Following with the same scheme of the precedent experiment, rectal temperature WBC and feed intake were observed for 3 consecutive days after the treatment. The intra-cervical inoculation of LPS not showed any systemic effects, as confirmed by the lack of changes in the parameters considered. In experiment 3, three groups (n=6) of New Zealand White does were inoculated intra-peritonally with 100 µg, close to the cervix region with 500 µg of E. coli LPS diluted in 2 ml of saline or only saline (control), 60 h before artificial insemination (AI). In intra-peritonally treated does and control were also determined the interleukine-1ß (IL-1ß) plasma concentrations. After 12 hours from AI, does were sacrificed and the reproductive tract was excised. The number of spermatozoa in uterine horns and oviducts was counted and histological evaluation in uterine tissues were performed. Histological examination showed an endometritis-like inflammation status in LPS-treated does and in these animals, the recovery of spermatozoa from uterine horns and oviducts were lower than control (P=0.05). IL-1ß plasma levels increased rapidly in LPS treated does respect to the control (P=0.01). These results suggest that a sub-acute or acute inflammation may cause infertility by compromising the uterine environment and/or impairing the sperm transport. In addition, the rabbit could be a useful LPS animal model for further studies of mechanisms involved in reproductive dysfunction mediated by infection and/or inflammation.