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Pioglitazone suppresses excessive follicular development in murine preantral follicles
Polycystic ovary syndrome (PCOS) is an endocrine disease that is common in women in their reproductive period. Patients with this disease suffer from anovulation and hyperandrogenism. Ovulation induction with exogenous gonadotropin often causes ovarian hyperstimulation syndrome because many small an...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717350/ https://www.ncbi.nlm.nih.gov/pubmed/31472696 http://dx.doi.org/10.1186/s13048-019-0556-7 |
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author | Nagao, Sachiko Baba, Tsuyoshi Fujibe, Yuya Adachi, Sayaka Ikeda, Keiko Morishita, Miyuki Kuno, Yoshika Honnma, Hiroyuki Endo, Toshiaki Kiya, Tamotsu Saito, Tsuyoshi |
author_facet | Nagao, Sachiko Baba, Tsuyoshi Fujibe, Yuya Adachi, Sayaka Ikeda, Keiko Morishita, Miyuki Kuno, Yoshika Honnma, Hiroyuki Endo, Toshiaki Kiya, Tamotsu Saito, Tsuyoshi |
author_sort | Nagao, Sachiko |
collection | PubMed |
description | Polycystic ovary syndrome (PCOS) is an endocrine disease that is common in women in their reproductive period. Patients with this disease suffer from anovulation and hyperandrogenism. Ovulation induction with exogenous gonadotropin often causes ovarian hyperstimulation syndrome because many small antral follicles pause in their growth. Treatment with insulin sensitizers is reportedly effective for both anovulation associated with PCOS, and suppression of excessive follicular growth; however, the underlying mechanism of action remains unknown. Although pioglitazone is known as an insulin sensitizer, it also has a potent modulator of cell growth and apoptosis irrespective of insulin resistance. To clarify the effect of pioglitazone on follicular growth, we performed in vitro culture of murine preantral follicles. Secondary follicles (100-160 μm in diameter) isolated from 6-week-old ICR mice were individually cultured for 13 days. Culture conditions were as follows: 1) follicle-stimulating hormone (FSH; 33 mIU/mL; control), 2) FSH plus dihydrotestosterone (DHT; 500 ng/mL), 3) FSH plus pioglitazone (5 ng/mL), and 4) FSH plus DHT/pioglitazone. Survival rate and follicle diameter were evaluated, and concentrations of estradiol (E2) and vascular endothelial growth factor (VEGF) in culture media were measured. mRNA expression of various growth-promoting factors and Vegf within follicles were also assessed. Although no significant differences were observed with regard to survival rate, follicle diameters on day 13 were significantly different. Compared with the control group, the DHT group showed enhanced growth, while groups administered pioglitazone showed stagnation of the accelerated growth induced by DHT. Although DHT treatment enhanced the expression of bone morphogenetic protein 2 (Bmp2) mRNA, pioglitazone exposure suppressed induction of Bmp2 mRNA by DHT. Vegf mRNA and protein expression were also significantly reduced when pioglitazone was added to culture media containing DHT. Administration of pioglitazone negatively affected follicular growth and VEGF levels, which may suppress excessive follicular growth and prevent ovarian hyperstimulation syndrome. |
format | Online Article Text |
id | pubmed-6717350 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-67173502019-09-06 Pioglitazone suppresses excessive follicular development in murine preantral follicles Nagao, Sachiko Baba, Tsuyoshi Fujibe, Yuya Adachi, Sayaka Ikeda, Keiko Morishita, Miyuki Kuno, Yoshika Honnma, Hiroyuki Endo, Toshiaki Kiya, Tamotsu Saito, Tsuyoshi J Ovarian Res Research Polycystic ovary syndrome (PCOS) is an endocrine disease that is common in women in their reproductive period. Patients with this disease suffer from anovulation and hyperandrogenism. Ovulation induction with exogenous gonadotropin often causes ovarian hyperstimulation syndrome because many small antral follicles pause in their growth. Treatment with insulin sensitizers is reportedly effective for both anovulation associated with PCOS, and suppression of excessive follicular growth; however, the underlying mechanism of action remains unknown. Although pioglitazone is known as an insulin sensitizer, it also has a potent modulator of cell growth and apoptosis irrespective of insulin resistance. To clarify the effect of pioglitazone on follicular growth, we performed in vitro culture of murine preantral follicles. Secondary follicles (100-160 μm in diameter) isolated from 6-week-old ICR mice were individually cultured for 13 days. Culture conditions were as follows: 1) follicle-stimulating hormone (FSH; 33 mIU/mL; control), 2) FSH plus dihydrotestosterone (DHT; 500 ng/mL), 3) FSH plus pioglitazone (5 ng/mL), and 4) FSH plus DHT/pioglitazone. Survival rate and follicle diameter were evaluated, and concentrations of estradiol (E2) and vascular endothelial growth factor (VEGF) in culture media were measured. mRNA expression of various growth-promoting factors and Vegf within follicles were also assessed. Although no significant differences were observed with regard to survival rate, follicle diameters on day 13 were significantly different. Compared with the control group, the DHT group showed enhanced growth, while groups administered pioglitazone showed stagnation of the accelerated growth induced by DHT. Although DHT treatment enhanced the expression of bone morphogenetic protein 2 (Bmp2) mRNA, pioglitazone exposure suppressed induction of Bmp2 mRNA by DHT. Vegf mRNA and protein expression were also significantly reduced when pioglitazone was added to culture media containing DHT. Administration of pioglitazone negatively affected follicular growth and VEGF levels, which may suppress excessive follicular growth and prevent ovarian hyperstimulation syndrome. BioMed Central 2019-08-31 /pmc/articles/PMC6717350/ /pubmed/31472696 http://dx.doi.org/10.1186/s13048-019-0556-7 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Nagao, Sachiko Baba, Tsuyoshi Fujibe, Yuya Adachi, Sayaka Ikeda, Keiko Morishita, Miyuki Kuno, Yoshika Honnma, Hiroyuki Endo, Toshiaki Kiya, Tamotsu Saito, Tsuyoshi Pioglitazone suppresses excessive follicular development in murine preantral follicles |
title | Pioglitazone suppresses excessive follicular development in murine preantral follicles |
title_full | Pioglitazone suppresses excessive follicular development in murine preantral follicles |
title_fullStr | Pioglitazone suppresses excessive follicular development in murine preantral follicles |
title_full_unstemmed | Pioglitazone suppresses excessive follicular development in murine preantral follicles |
title_short | Pioglitazone suppresses excessive follicular development in murine preantral follicles |
title_sort | pioglitazone suppresses excessive follicular development in murine preantral follicles |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717350/ https://www.ncbi.nlm.nih.gov/pubmed/31472696 http://dx.doi.org/10.1186/s13048-019-0556-7 |
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