Pioglitazone suppresses excessive follicular development in murine preantral follicles.

Abstract

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.

• Authors: Sachiko Nagao, Tsuyoshi Baba, Yuya Fujibe, Sayaka Adachi, Keiko Ikeda, Miyuki Morishita, Yoshika Kuno, Hiroyuki Honnma, Toshiaki Endo, Tamotsu Kiya, Tsuyoshi Saito
• Journal: Journal of ovarian research (J Ovarian Res) Vol. 12 Issue 1 Pg. 82 (Aug 31 2019) ISSN: 1757-2215 [Electronic] England
• PMID: 31472696 (Publication Type: Journal Article)

Chemical References

• Androgens
• Bmp2 protein, mouse
• Bone Morphogenetic Protein 2
• Hypoglycemic Agents
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• Dihydrotestosterone
• Estradiol
• Pioglitazone

Topics

• Androgens (pharmacology)
• Animals
• Bone Morphogenetic Protein 2 (genetics)
• Dihydrotestosterone (pharmacology)
• Estradiol (metabolism)
• Female
• Hypoglycemic Agents (pharmacology)
• Mice, Inbred ICR
• Ovarian Follicle (drug effects, growth & development, metabolism)
• Pioglitazone (pharmacology)
• Vascular Endothelial Growth Factor A (genetics, metabolism)