Clin Exp Reprod Med.  2021 Sep;48(3):245-254. 10.5653/cerm.2020.04112.

Alteration of TGFB1, GDF9, and BMPR2 gene expression in preantral follicles of an estradiol valerate-induced polycystic ovary mouse model can lead to anovulation, polycystic morphology, obesity, and absence of hyperandrogenism

• Asghari R
• Shokri-Asl V
• Rezaei H
• Tavallaie M
• Khafaei M
• Abdolmaleki A
• Majdi Seghinsara A

• KMID: 2520001
• DOI: http://doi.org/10.5653/cerm.2020.04112

Abstract

Objective
In humans, polycystic ovary syndrome (PCOS) is an androgen-dependent ovarian disorder. Aberrant gene expression in folliculogenesis can arrest the transition of preantral to antral follicles, leading to PCOS. We explored the possible role of altered gene expression in preantral follicles of estradiol valerate (EV) induced polycystic ovaries (PCO) in a mouse model.
Methods
Twenty female balb/c mice (8 weeks, 20.0±1.5 g) were grouped into control and PCO groups. PCO was induced by intramuscular EV injection. After 8 weeks, the animals were killed by cervical dislocation. Blood serum (for hormonal assessments using the enzyme-linked immunosorbent assay technique) was aspirated, and ovaries (the right ovary for histological examinations and the left for quantitative real-time polymerase) were dissected.
Results
Compared to the control group, the PCO group showed significantly lower values for the mean body weight, number of preantral and antral follicles, serum levels of estradiol, luteinizing hormone, testosterone, and follicle-stimulating hormone, and gene expression of TGFB1, GDF-9 and BMPR2 (p<0.05). Serum progesterone levels were significantly higher in the PCO animals than in the control group (p<0.05). No significant between-group differences (p>0.05) were found in BMP6 or BMP15 expression.
Conclusions
In animals with EV-induced PCO, the preantral follicles did not develop into antral follicles. In this mouse model, the gene expression of TGFB1, GDF9, and BMPR2 was lower in preantral follicles, which is probably related to the pathologic conditions of PCO. Hypoandrogenism was also detected in this EV-induced murine PCO model.

Keyword

Polycystic ovary syndrome; Multicystic morphology of ovary; Transforming growth factor-β1; Bone morphogenetic protein 6; Bone morphogenetic protein 15; Growth differentiation factor 9; BMPRII; Estradiol valerate; Folliculogenesis; Preantral follicles