Follicular Development and Ovulation in Macrophage Colony-Stimulating Factor-Deficient Mice Homozygous for the Osteopetrosis (Op) Mutation1

Abstract

To clarify the role of macrophages and macrophage colony-stimulating factor (M-CSF) in follicular development and ovulation, the processes of folliculogenesis and ovulation, numerical changes in macrophages, and proliferative capacity of granulosa cells were examined in op/op mice before or after daily M-CSF administration. The natural estrous cycle was determined daily by means of vaginal smears. The number of ovulated ova in both fallopian tubes was significantly smaller in op/op mice than in normal littermates. Such ova markedly increased in number after daily M-CSF administration. The numbers of both antral and mature follicles in the proestrous ovary were markedly lower in op/op mice than in the controls and increased after daily M-CSF administration. Flash-labeling with [3H]thymidine showed that the proliferative capacity of granulosa cells in antral follicles was reduced in op/op mice but elevated after daily M-CSF administration. Numbers of granulosa cells and macrophages in the antral follicles were significantly decreased in op/op mice but were increased after M-CSF treatment. All these data provide evidence that macrophages are implicated in the process of folliculogenesis and ovulation.

The Role of Interleukin-6 in the Regulation of Granulosa Cell Apoptosis During Follicular Atresia in Pig Ovaries

“…Cytokines produced by immune cells such as macrophages are involved in various physiological events, such as follicular development, atresia, ovulation, and luteolysis in ovaries [33,34]. Macrophages are present in the ovaries of many animal species, but it has not been clear whether they are located in the theca layer, granulosa layer, or follicular antrum [35][36][37]. In the present study, we clearly demonstrated that macrophages are located only in theca external and internal layers of healthy follicles, and that they are not in the granulosa layer or follicular antrum.…”

Endometriosis and Infertility: A Multi‐cytokine Imbalance Versus Ovulation, Fertilization and Early Embryo Development

“…Among these cytokines, IL-10, IL-3 and GM-CSF facilitate embryo growth (Athanassakis et al 1987) whereas IL-6 is involved in the inflammatory reaction during implantation. During the preparative stage of embryo implantation, GM-CSF and IL-3 are present in the endometrium, IL-10 in the endometrium/ myometrium, IL-1 and CSF-1 are produced by the mesometrium, uterine epithelium and endometrium, TNF-a and IFN-g are present in the mesometrium and IL-6 is found to be also produced by endometrium and is present in the endometrium/myometrium during implantation (Adashi 1998, Araki et al 1996.…”

Analysis of the Mouse CSF-1 Gene Promoter in a Transgenic Mouse Model1

“…Stimulation of resident macrophages in multiple tissues contributes to the diverse biological effects of CSF-1 on male and female fertility, trophoblast implantation, mammary gland development during pregnancy, dermal thickness, and neural function (Araki et al 1996;Cohen et al 1996;Pollard and Henninghausen 1996;Pollard and Stanley 1996;Pollard 1997). CSF-1 mRNA is expressed in multiple tissues in a tissue-specific manner in rodents and humans (Rajavashisth et al 1987;Roth and Stanley 1995).…”