Decidualized Endometrial Stromal Cells Promote Mitochondrial Beta-Oxidation to Produce the Octanoic Acid Required for Implantation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Tissue Collection and Primary Culture of HESCs
2.2. Decidualization of HESCs
2.3. LC/FT-MS
2.4. Beta-Oxidation Assay
2.5. RNA Extraction and Expression
2.6. Invasion Assay
3. Results
3.1. Effects of Decidualizing Stimuli Using 8-br-cAMP and MPA in HESCs
3.2. Promoted Production of Octanoic Acid in the Culture Medium of Decidualized HESCs Revealed by Free Fatty Acid Profile Analysis
3.3. Fatty Acid Beta-Oxidation Activity Increased in Decidualized HESCs
3.4. Expression of Genes Related to Fatty Acid Metabolism in Decidualized HESCs
3.5. Tendency to Promote Invasion by Octanoic Acid in a Trophoblast Cell Line
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Winship, A.; Cuman, C.; Rainczuk, K.; Dimitriadis, E. Fibulin-5 is upregulated in decidualized human endometrial stromal cells and promotes primary human extravillous trophoblast outgrowth. Placenta 2015, 36, 1405–1411. [Google Scholar] [CrossRef] [PubMed]
- Brosens, J.J.; Pijnenborg, R.; Brosens, I.A. The myometrial junctional zone spiral arteries in normal and abnormal pregnancies: A review of the literature. Am. J. Obstet. Gynecol. 2002, 187, 1416–1423. [Google Scholar] [CrossRef] [PubMed]
- Gellersen, B.; Brosens, I.A.; Brosens, J.J. Decidualization of the human endometrium: Mechanisms, functions, and clinical perspectives. Semin. Reprod. Med. 2007, 25, 445–453. [Google Scholar] [CrossRef] [PubMed]
- Gellersen, B.; Brosens, J.J. Cyclic decidualization of the human endometrium in reproductive health and failure. Endocr. Rev. 2014, 35, 851–905. [Google Scholar] [CrossRef] [PubMed]
- Kajihara, T.; Tanaka, K.; Oguro, T.; Tochigi, H.; Prechapanich, J.; Uchino, S.; Itakura, A.; Sućurović, S.; Murakami, K.; Brosens, J.J.; et al. Androgens modulate the morphological characteristics of human endometrial stromal cells decidualized in vitro. Reprod. Sci. 2014, 21, 372–380. [Google Scholar] [CrossRef] [PubMed]
- Gellersen, B.; Wolf, A.; Kruse, M.; Schwenke, M.; Bamberger, A.M. Human endometrial stromal cell-trophoblast interactions: Mutual stimulation of chemotactic migration and promigratory roles of cell surface molecules CD82 and CEACAM1. Biol. Reprod. 2013, 88, 80. [Google Scholar] [CrossRef] [PubMed]
- Quenby, S.; Brosens, J.J. Human implantation: A tale of mutual maternal and fetal attraction. Biol. Reprod. 2013, 88, 81. [Google Scholar] [CrossRef] [PubMed]
- Frolova, A.; Flessner, L.; Chi, M.; Kim, S.T.; Foyouzi-Yousefi, N.; Moley, K.H. Facilitative glucose transporter type 1 is differentially regulated by progesterone and estrogen in murine and human endometrial stromal cells. Endocrinology 2009, 150, 1512–1520. [Google Scholar] [CrossRef]
- Frolova, A.I.; Moley, K.H. Quantitative analysis of glucose transporter mRNAs in endometrial stromal cells reveals critical role of GLUT1 in uterine receptivity. Endocrinology 2011, 152, 2123–2128. [Google Scholar] [CrossRef]
- von Wolff, M.; Ursel, S.; Hahn, U.; Steldinger, R.; Strowitzki, T. Glucose transporter proteins (GLUT) in human endometrium: Expression, regulation, and function throughout the menstrual cycle and in early pregnancy. J. Clin. Endocrinol. Metab. 2003, 88, 3885–3892. [Google Scholar] [CrossRef]
- Stubbs, C.D.; Smith, A.D. The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function. Biochim. Biophys. Acta 1984, 779, 89–137. [Google Scholar] [CrossRef] [PubMed]
- Killeen, A.P.; Diskin, M.G.; Morris, D.G.; Kenny, D.A.; Waters, S.M. Endometrial gene expression in high- and low-fertility heifers in the late luteal phase of the estrous cycle and a comparison with midluteal gene expression. Physiol. Genom. 2016, 48, 306–319. [Google Scholar] [CrossRef] [PubMed]
- Killeen, A.P.; Morris, D.G.; Kenny, D.A.; Mullen, M.P.; Diskin, M.G.; Waters, S.M. Global gene expression in endometrium of high and low fertility heifers during the mid-luteal phase of the estrous cycle. BMC. Genom. 2014, 15, 234. [Google Scholar] [CrossRef]
- Ruiz-Alonso, M.; Blesa, D.; Simón, C. The genomics of the human endometrium. Biochim. Biophys. Acta 2012, 1822, 1931–1942. [Google Scholar] [CrossRef]
- Tsai, J.H.; Chi, M.M.; Schulte, M.B.; Moley, K.H. The fatty acid beta-oxidation pathway is important for decidualization of endometrial stromal cells in both humans and mice. Biol. Reprod. 2014, 90, 34. [Google Scholar] [CrossRef]
- Yamada, M.; Takanashi, K.; Hamatani, T.; Hirayama, A.; Akutsu, H.; Fukunaga, T.; Ogawa, S.; Sugawara, K.; Shinoda, K.; Soga, T.; et al. A medium-chain fatty acid as an alternative energy source in mouse preimplantation development. Sci. Rep. 2012, 2, 930. [Google Scholar] [CrossRef] [PubMed]
- Kajihara, T.; Jones, M.; Fusi, L.; Takano, M.; Feroze-Zaidi, F.; Pirianov, G.; Mehmet, H.; Ishihara, O.; Higham, J.M.; Lam, E.W.; et al. Differential expression of FOXO1 and FOXO3a confers resistance to oxidative cell death upon endometrial decidualization. Mol. Endocrinol. 2006, 20, 2444–2455. [Google Scholar] [CrossRef] [PubMed]
- Christian, M.; Zhang, X.; Schneider-Merck, T.; Unterman, T.G.; Gellersen, B.; White, J.O.; Brosens, J.J. Cyclic AMP-induced forkhead transcription factor, FKHR, cooperates with CCAAT/enhancer-binding protein beta in differentiating human endometrial stromal cells. J. Biol. Chem. 2002, 277, 20825–20832. [Google Scholar] [CrossRef]
- Leitao, B.; Jones, M.C.; Fusi, L.; Higham, J.; Lee, Y.; Takano, M.; Goto, T.; Christian, M.; Lam, E.W.; Brosens, J.J. Silencing of the JNK pathway maintains progesterone receptor activity in decidualizing human endometrial stromal cells exposed to oxidative stress signals. FASEB J. 2010, 24, 1541–1551. [Google Scholar] [CrossRef]
- Ozaki, H.; Nakano, Y.; Sakamaki, H.; Yamanaka, H.; Nakai, M. Basic eluent for rapid and comprehensive analysis of fatty acid isomers using reversed-phase high performance liquid chromatography/Fourier transform mass spectrometry. J. Chromatogr. A 2019, 1585, 113–120. [Google Scholar] [CrossRef]
- Mizuno, Y.; Ninomiya, Y.; Nakachi, Y.; Iseki, M.; Iwasa, H.; Akita, M.; Tsukui, T.; Shimozawa, N.; Ito, C.; Toshimori, K.; et al. Tysnd1 deficiency in mice interferes with the peroxisomal localization of PTS2 enzymes, causing lipid metabolic abnormalities and male infertility. PLOS Genet. 2013, 9, e1003286. [Google Scholar] [CrossRef] [PubMed]
- Graham, C.H.; Hawley, T.S.; Hawley, R.G.; MacDougall, J.R.; Kerbel, R.S.; Nelson, K.; Lala, P.K. Establishment and characterization of first trimester human trophoblast cells with extended lifespan. Exp. Cell Res. 1993, 206, 204–211. [Google Scholar] [CrossRef] [PubMed]
- Eaton, S.; Bartlett, K.; Pourfarzam, M. Mammalian mitochondrial beta-oxidation. Biochem. J. 1996, 320, 345–357. [Google Scholar] [CrossRef] [PubMed]
- Leonard, P.H.; Charlesworth, M.C.; Benson, L.; Walker, D.L.; Fredrickson, J.R.; Morbeck, D.E. Variability in protein quality used for embryo culture: Embryotoxicity of the stabilizer octanoic acid. Fertil. Steril. 2013, 100, 544–549. [Google Scholar] [CrossRef] [PubMed]
- Fredrickson, J.; Krisher, R.; Morbeck, D.E. The impact of the protein stabilizer octanoic acid on embryonic development and fetal growth in a murine model. J. Assist. Reprod. Genet. 2015, 32, 1517–1524. [Google Scholar] [CrossRef] [PubMed]
- Menkhorst, E.M.; Lane, N.; Winship, A.L.; Li, P.; Yap, J.; Meehan, K.; Rainczuk, A.; Stephens, A.; Dimitriadis, E. Decidual-secreted factors alter invasive trophoblast membrane and secreted proteins implying a role for decidual cell regulation of placentation. PLoS ONE 2012, 7, e31418. [Google Scholar] [CrossRef] [PubMed]
- Wathes, D.C.; Abayasekara, D.R.; Aitken, R.J. Polyunsaturated fatty acids in male and female reproduction. Biol. Reprod. 2007, 77, 190–201. [Google Scholar] [CrossRef]
- Sturmey, R.G.; Reis, A.; Leese, H.J.; McEvoy, T.G. Role of fatty acids in energy provision during oocyte maturation and early embryo development. Reprod. Domest. Anim. 2009, 44, 50–58. [Google Scholar] [CrossRef]
- Norwitz, E.R.; Schust, D.J.; Fisher, S.J. Implantation and the survival of early pregnancy. N. Engl. J. Med. 2001, 345, 1400–1408. [Google Scholar] [CrossRef]
- Ye, Q.; Cai, S.; Wang, S.; Zeng, X.; Ye, C.; Chen, M.; Zeng, X.; Qiao, S. Maternal short and medium chain fatty acids supply during early pregnancy improves embryo survival through enhancing progesterone synthesis in rats. J. Nutr. Biochem. 2019, 69, 98–107. [Google Scholar] [CrossRef]
- Wang, C.; Wang, J.; Chen, K.; Pang, H.; Li, X.; Zhu, J.; Ma, Y.; Qiu, T.; Li, W.; Xie, J.; et al. Caprylic acid (C8:0) promotes bone metastasis of prostate cancer by dysregulated adipo-osteogenic balance in bone marrow. Cancer Sci. 2020, 111, 3600–3612. [Google Scholar] [CrossRef] [PubMed]
- Vilella, F.; Ramirez, L.B.; Simón, C. Lipidomics as an emerging tool to predict endometrial receptivity. Fertil. Steril. 2013, 99, 1100–1106. [Google Scholar] [CrossRef] [PubMed]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Mizuno, Y.; Tamaru, S.; Tochigi, H.; Sato, T.; Kishi, M.; Ohtake, A.; Ishihara, O.; Kajihara, T. Decidualized Endometrial Stromal Cells Promote Mitochondrial Beta-Oxidation to Produce the Octanoic Acid Required for Implantation. Biomolecules 2024, 14, 1014. https://doi.org/10.3390/biom14081014
Mizuno Y, Tamaru S, Tochigi H, Sato T, Kishi M, Ohtake A, Ishihara O, Kajihara T. Decidualized Endometrial Stromal Cells Promote Mitochondrial Beta-Oxidation to Produce the Octanoic Acid Required for Implantation. Biomolecules. 2024; 14(8):1014. https://doi.org/10.3390/biom14081014
Chicago/Turabian StyleMizuno, Yumi, Shunsuke Tamaru, Hideno Tochigi, Tomomi Sato, Miyuko Kishi, Akira Ohtake, Osamu Ishihara, and Takeshi Kajihara. 2024. "Decidualized Endometrial Stromal Cells Promote Mitochondrial Beta-Oxidation to Produce the Octanoic Acid Required for Implantation" Biomolecules 14, no. 8: 1014. https://doi.org/10.3390/biom14081014