Polycystic ovary syndrome: Long-term effects on fertility and uterine lesions

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. In this study, we aimed to investigate the long-term effects of PCOS. We assessed fertility at 3 months of age and uterine histomorphology along with endocrine status at 6 and 24 months of age in an experimental model. PCOS was induced in female Wistar rats from 21 to 40 days of age by subcutaneous injection of dehydroepiandrosterone (6 mg/100 g bw). After treatment, rats were separated into groups and euthanized on gestational day 18 (GD18), 6 months and 24 months of age. Fertility test was performed on GD18 and no changes were observed in the PCOS rats. At 6 months of age, PCOS rats showed uterine lesions associated with a higher serum 17-β estradiol (E2)/progesterone (P4) ratio. At 24 months of age, PCOS rats had a higher incidence of luminal hyperplasia and a greater number of glands with metaplasia and conglomerates of glands. This was associated with increased serum E2/P4 ratio, uterine steroidogenic enzymes (steroid sulfatase, 5α-reductase type I) and estrogen receptor alpha expression. In addition, an increased infiltration of eosinophils in the uterus was observed, suggesting an estrogenic effect. These results show that PCOS induced early in life alters the uterine endocrine status in the long term, suggesting increased uterine exposure and sensitivity to estrogens. Taken together, these findings may explain the increased incidence/multiplicity of uterine lesions observed in the PCOS group.