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

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.

Single intratesticular injection of blood‐serum‐derived exosomes can potentially alleviate testopathy following testicular torsion

“…no. 108666) was employed to measure the Tes levels in blood serum using the routine procedure of Asghari et al 13 …”

Cocktails of NSAIDs and 17α Ethinylestradiol at Environmentally Relevant Doses in Drinking Water Alter Puberty Onset in Mice Intergenerationally

“…Moreover, BMPR2 and its ligand BMP15 are associated with or are the cause of POI [ 144 ]. Similarly, alteration of BMPR2 gene expression can lead to a polycystic ovary in mice without hyperandrogenism [ 145 ].…”

Follicular development and ovary aging: single-cell studies

“…Reduced progesterone levels in FF in the PCOS group may be attributable to the suppression of luteinizing hormone synthesis in GC and TC by GDF9 and BMP15, which are powerful inhibitors of luteinizing hormone in follicular cells and prevent premature luteinization through BMPR2 in PCOS follicular cells [145]. In mice with estradiol valerate-induced polycystic ovaries (PCO), preantral follicle development was found to have ceased, and gene expression of TGFB1, GDF9, and BMPR2 was lower in preantral follicles, which may be relevant to the pathologic conditions of PCO [146]. Interestingly, the expression of GDF-9 in PCOS GC was found to decrease in cases where ovulation induction treatment was received.…”