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Cellular expression of monocarboxylate transporters in the female reproductive organ of mice: implications for the genital lactate shuttle

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Abstract

The present study examined the cellular localization of monocarboxylate transporters (MCTs), glucose transporters (GLUTs), and some glycolysis-related molecules in the murine female genital tract to demonstrate existence of lactate/pyruvate-dependent energy systems. MCT1, a major MCT subtype, was localized selectively in the ovarian granulosa, oviductal-ciliated cells, and vaginal epithelium; all localizations were associated with intense expressions of glycolytic enzymes. MCT1 was localized in the cell membrane of granulosa cells, including fine processes extending from cumulus cells toward oocytes. The cumulus cells and oocytes showed intense signals for lactate dehydrogenase (LDH)-A and -B, respectively. The basolateral membrane of oviductal-ciliated cells expressed MCT4 as well as MCT1, while adjacent non-ciliated cells contained an intense immunoreactivity for aldolase-C, a glycolytic enzyme. The expression of GLUTs in the ovary was generally weak with an intense expression of GLUT1 only in some vascular endothelia. The oviductal epithelium expressed GLUT1 and GLUT3, respectively, in the basolateral and apical membrane of non-ciliated cells. In the vagina, the basal layers of epithelium were immunolabeled for MCT1 with the entire length of cell membrane, and expressed abundantly both GLUT1 and LDH-A. The findings correspond well with the rich existence of lactate in the genital fluids and strongly suggest the active transport of lactate/pyruvate in the female reproductive tract, which provides favorable conditions for oocytes, sperms, and zygotes.

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Acknowledgments

This study is supported by grants from the Ministry of Education, Science, Sport, and Culture, Japan (No. 22590184 to T. I.) and The Uehara Memorial Foundation (to T. I.).

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Authors and Affiliations

  1. Laboratory of Histology and Cytology, Graduate School of Medicine, Hokkaido University, Kita 15-Nishi 7, Sapporo, 060-8638, Japan

    Takuya Kuchiiwa, Junko Nio-Kobayashi, Hiromi Takahashi-Iwanaga & Toshihiko Iwanaga

  2. Meiji Dairies Research Chair, Creative Research Initiative “Sousei” (CRIS), Hokkaido University, Kita 21-Nishi 10, Sapporo, 001-0021, Japan

    Takaji Yajima

Authors
  1. Takuya Kuchiiwa
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  2. Junko Nio-Kobayashi
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  3. Hiromi Takahashi-Iwanaga
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  5. Toshihiko Iwanaga
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Corresponding author

Correspondence to Toshihiko Iwanaga.

Electronic supplementary material

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418_2011_794_MOESM1_ESM.tif

Supplemental information-1. In situ hybridization analysis for mRNA expressions of GLUT1–GLUT5. Two sections (a, b) from the same mouse are hybridized for GLUT1 and GLUT3 (c and d are dark-field images of a and b). GLUT 1 and GLUT3 are expressed mainly in the proximal (ampulla, Amp) and distal (isthmus, Isth) regions, respectively. No significant signals are visible in the ovary. Bar 200 μm. Figures e–h show X-ray film images for GLUT2–GLUT5 mRNAs. The ovary, oviduct, and uterus are mounted on the glass slides together with tissues for positive control (K: kidney, L: liver, B: brain, M: muscle, I: intestine). Intense signals in the oviduct (indicated by arrows) are found only for GLUT3, with faint signals for GLUT4 in the oviduct. Each glass slide contains four sections serially cut from the female reproductive organ. (TIFF 1384 kb)

418_2011_794_MOESM2_ESM.tif

Supplemental information-2. Immunohistochemistry for GLUT1 in the ovary and oviduct. The GLUT1 immunoreactivity in the ovary is restricted to some vascular endothelia (arrows in a). In the oviduct (b), the GLUT1 immunoreactivity is found in the distal region of the ampulla (arrow) but not the proximal part of the ampulla (Amp), including the infundibulum (Inf). (TIFF 561 kb)

418_2011_794_MOESM3_ESM.tif

Supplemental information-3. In situ hybridization on a single section for LDH-A mRNA in the oviduct. Bright field (a) and dark field (b) images show an intense expression of LDH-A in the isthmus of oviduct and the luminal epithelium of uterus. Inf: infundibulum (TIFF 728 kb)

418_2011_794_MOESM4_ESM.tif

Supplemental information-4. Three serial paraffin sections from the vagina at different estrus stages are stained for periodic acid-Schiff (PAS) reaction (a–c), MCT1 (d–f), and GLUT1 (g–i). The immunoreactivity for MCT1 is more intense at met-estrus to di-estrus while the GLUT1 immunoreactivity increases in intensity at pro-estrus to estrus. (TIFF 1054 kb)

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Kuchiiwa, T., Nio-Kobayashi, J., Takahashi-Iwanaga, H. et al. Cellular expression of monocarboxylate transporters in the female reproductive organ of mice: implications for the genital lactate shuttle. Histochem Cell Biol 135, 351–360 (2011). https://doi.org/10.1007/s00418-011-0794-2

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