The acute effect of propanil on reproductive hormones, ovarian gene expression and splenic cells in C57Bl/6 female mice

Abstract

The acute effect of propanil on reproductive hormones, ovarian gene expression and splenic cells in C57Bl/6 female mice Malia Danielle Berg Earlier evidence indicates exposure to propanil, a post-emergent herbicide used on rice and wheat fields, increases the number of antibody-secreting cells (ASC) in the spleen of mice after immunization with heat-killed Streptococcus pneumoniae (HKSP, 2x108 CFU). Interestingly, an intact hypothalamic-pituitary-gonadal (HPG) axis is required for this immune response assessed on day 7-10 after immunization in female mice. Hence, an overarching premise is that propanil arbitrates the connection between the reproductive and immune system by altering the concentration of hormones involved in the HPG axis, which may then affect the populations of splenic cells. Hypotheses were tested with C57Bl/6 female mice vaccinated with HKSP and assigned among four treatment groups (6 mice each) in a 2x2 factorial arrangement. The first factor represented propanil treatment (propanil, control), and the second factor represented two periods (24h, 72h) of collection for blood, spleen, ovaries, and oviducts after immunization. At 24h, propanil decreased the number of splenocytes contrary to increased cell populations at day 7-10 observed in earlier experiments. Also, propanil increased serum concentrations of prolactin and progesterone but decreased estradiol, corroborated by corresponding changes in mRNA for steroid synthesis in ovaries. To determine if these effects depend on gonadotropin-releasing hormone (GnRH) receptor binding, we utilized the GnRH antagonist (antide; 60 μg s.q.), given to C57Bl/6 female mice before the same immunization with HKSP. In ovaries, antide increased gene expression of inflammatory and anti-inflammatory cytokines and markers (Csf1, Cxcl1, Cxcl10, Il-10, Irf-1, Tlr2), interacted with propanil effect in HKSP-challenged mice on the expression of serum amyloid A by reducing propanil’s effects. In the spleen, antide decreased the number of T-cells, and in the presence of HKSP decreased the number of B-cells and the percentage of monocytes and macrophages. Thus, GnRH receptors may be necessary for the acute responses (24 hours) to propanil and support a hypothesis that immune and reproductive systems interact in female mice challenged with the bacterial vaccine.