Macrophages: important accessory cells for reproductive function

Macrophages are found throughout reproductive tissues. To determine their role(s), we have studied mice homozygous for a null mutation (Csfm op ) in the gene encoding the major macrophage growth factor, colony‐stimulating factor‐1 (CSF‐1). Both male and female Csfm op /Csfm op mice have fertility defects. Males have low sperm number and libido as a consequence of dramatically reduced circulating testosterone. Females have extended estrous cycles and poor ovulation rates. CSF‐1 is the principal growth factor regulating macrophage populations in the testis, male accessory glands, ovary, and uterus. However, analyses of CSF‐1 nullizygous mice suggest that the primary reproductive defect is in the development of feedback regulation of the hypothalamic‐pituitary axis. Although not correlating with deficiencies of microglia populations, electrophysiological investigations indicate an impairment of neuronal responses. This suggests that microglia, under the influence of CSF‐1, act to organize neuronal connectivity during development and that the absence of this function results in a perturbation of the hypothalamicpituitary‐gonadal axis. Macrophages also appear to have functions in the differentiated tissues of the reproductive system, including having a positive influence on steroidogenic cells. These data suggest that macrophages, through their trophic functions, can be considered as essential accessory cells for normal reproductive functioning. J. Leukoc. Biol. 66:765–772; 1999.