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 hypothalamic-pituitary-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.
Cohen
P E
PE
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Nishimura
K
K
Zhu
L
L
Pollard
J W
JW
D000818:Animals; D005260:Female; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D010053:Ovary / Q000166:cytology; D012098:Reproduction / Q000502:physiology*; D013737:Testis / Q000166:cytology; D014599:Uterus / Q000166:cytology
D016173:Macrophage Colony-Stimulating Factor