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Phagocytosis mechanism of apoptotic granulosa cells regulated by milk-fat globule-EGF factor 8

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Abstract

In the process of ovary sexual maturation, most immature ovarian follicles degrade into atretic follicles accompanied by apoptosis in granulosa cells. Macrophages can recognize apoptotic cells through specific binding with phosphatidylserine (PS), exposed on the surface of apoptotic cells, which is mediated by milk-fat globule-EGF factor 8 (MFG-E8). In the present research, we examined the involvement of the MFG-E8-dependent phagocytosis system in the atretic follicles of developing mouse ovaries. The number of atretic follicles and DNA-fragmented granulosa cells significantly increased in B6C3F1 mice during 2 to 6 weeks. Chromatin-condensed granulosa cells were engulfed by macrophages, which existed in the stroma or atretic follicles, or by neighboring normal granulosa cells. MFG-E8 mRNA increased in ovaries during 2 to 6 weeks, and immunoreactivity of MFG-E8 was detected at the surface of apoptotic cells existing around the antrum. Immunoelectron microscopic study revealed MFG-E8-positive signals on the membrane of apoptotic cells near macrophages, but apoptotic cells engulfed by neighboring granulosa cells showed few signals. Anti-Fas antibody elevated the annexin-V-positive reaction in isolated granulosa cells from 3-week-old mouse ovaries. MFG-E8 seems to act on the phagocytosis of apoptotic granulosa cells via macrophages and contribute to the regression process of atretic follicles.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Division of Life Sciences, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan

    Mayumi Naka, Yuko Ito, Masa-Aki Shibata & Yoshinori Otsuki

  2. Laboratory of Laboratory Animal Science, Division of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan

    Ken Kusakabe & Ai Takeshita

  3. Laboratory of Toxicology, Division of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan

    Hiroshi Nakagawa

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  1. Mayumi Naka
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  2. Ken Kusakabe
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  3. Ai Takeshita
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  4. Hiroshi Nakagawa
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  5. Yuko Ito
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  6. Masa-Aki Shibata
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  7. Yoshinori Otsuki
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Correspondence to Yoshinori Otsuki.

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Naka, M., Kusakabe, K., Takeshita, A. et al. Phagocytosis mechanism of apoptotic granulosa cells regulated by milk-fat globule-EGF factor 8. Med Mol Morphol 42, 143–149 (2009). https://doi.org/10.1007/s00795-009-0452-0

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  • DOI: https://doi.org/10.1007/s00795-009-0452-0

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