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Evidence for existence of insulin-like factor 3 (INSL3) hormone-receptor system in the ovarian corpus luteum and extra-ovarian reproductive organs during pregnancy in goats

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Abstract

Insulin-like factor 3 (INSL3), initially described as a male hormone, is expressed in female reproductive organs during the estrous cycle and pregnancy but its function has not yet been established. This study explores the function of INSL3 in pregnant Saanen goats by characterizing the expression dynamics of INSL3 and its receptor, relaxin family peptide receptor 2 (RXFP2) and by demonstrating specific INSL3 binding in reproductive organs, using molecular and immunological approaches and ligand-receptor interaction assays. We demonstrate that the corpus luteum (CL) acts as both a source and target of INSL3 in pregnant goats, while extra-ovarian reproductive organs serve as additional INSL3 targets. The expression of INSL3 and RXFP2 in the CL reached maximum levels in middle pregnancy, followed by a decrease in late pregnancy; in contrast, RXFP2 expression levels in extra-ovarian reproductive organs were higher in the mammary glands but lower in the uterus, cervix and placenta and did not significantly change during pregnancy. The functional RXFP2 enabling INSL3 to bind was identified as an ~ 85 kDa protein in both the CL and mammary glands and localized in large and small luteal cells in the CL and in tubuloalveolar and ductal epithelial cells in the mammary glands. Additionally, INSL3 also bound to multiple cell types expressing RXFP2 in the uterus, cervix and placenta in a hormone-specific and saturable manner. These results provide evidence that an active intra- and extra-ovarian INSL3 hormone-receptor system operates during pregnancy in goats.

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Acknowledgments

The authors thank the staff at Tohoku University and Shinshu University for their help in caring and collecting tissue samples from goats. We also thank Ms Yoko Murata for her assistance with the qRT-PCR analysis.

Funding

This work was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (no. 18H02327 to T. Kohsaka).

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Authors and Affiliations

  1. Department of Applied Life Sciences, Faculty of Agriculture, Shizuoka University, Shizuoka, 422-8529, Japan

    Ali Mohammed Pitia, Itaru Minagawa & Tetsuya Kohsaka

  2. Department of Life Sciences, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Hiroshima, 727-0023, Japan

    Yasuyuki Abe

  3. Cooperative Department of Veterinary Medicine, Faculty of Agriculture, Iwate University, Iwate, 020-8550, Japan

    Keiichiro Kizaki & Kazuyoshi Hashizume

  4. Education and Research Center of Alpine Field Science, Faculty of Agriculture, Shinshu University, Nagano, 399-4598, Japan

    Koh-ichi Hamano

  5. Division of Animal Science, Kitasato University School of Veterinary Medicine, Aomori, 034-8628, Japan

    Hiroshi Sasada

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  1. Ali Mohammed Pitia
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  2. Itaru Minagawa
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  3. Yasuyuki Abe
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  4. Keiichiro Kizaki
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  5. Koh-ichi Hamano
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  6. Hiroshi Sasada
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  7. Kazuyoshi Hashizume
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  8. Tetsuya Kohsaka
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Correspondence to Tetsuya Kohsaka.

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Animal handling and all experimental procedures were performed according to the Health Guidelines for the Care and Use of Experimental Animals of Tohoku University, Shinshu University and Shizuoka University.

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Pitia, A.M., Minagawa, I., Abe, Y. et al. Evidence for existence of insulin-like factor 3 (INSL3) hormone-receptor system in the ovarian corpus luteum and extra-ovarian reproductive organs during pregnancy in goats. Cell Tissue Res 385, 173–189 (2021). https://doi.org/10.1007/s00441-021-03410-1

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