Polycystic Ovary Syndrome (PCOS) Models
Polycystic Ovary Syndrome (PCOS) is a highly heterogeneous disease, and its complex clinical manifestations can be divided into reproductive and metabolic aspects. Reproductive manifestations include follicular developmental disorders, oligoovulation or anovulation, hyperandrogenemia and associated acne and hirsutism, as well as abnormal secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Metabolic manifestations primarily include obesity, hyperinsulinemia, insulin resistance, adipocyte hypertrophy, dyslipidemia, and fatty liver disease. Additionally, patients have a significantly increased risk of cardiovascular diseases, type 2 diabetes, and metabolic syndrome.
BKS-Lepr-/- (BKS-db, Strain NO. T002407) and B6-Lep-/- (ob/ob, Strain NO. T001461) mice develop spontaneous obesity and hyperglycemia, making them commonly used diabetic models that align with the metabolic phenotype of PCOS. To validate the reproductive phenotype in these mice, female B6-Lepr-/-, female BKS-Lepr-/-, and female B6-Lep-/- mice were subjected to vaginal smear for 10 consecutive days at 8 weeks of age to collect their estrous cycles, which were then compared with those of healthy B6 mice. At 12 and 16 weeks of age, the ovaries and uteri were harvested and weighed, and the ovaries were subjected to H&E staining to count the number of corpora lutea.
1. Study design
Figure 1. Study designs
2. BKS-Lepr-/- and B6-Lep-/- display disrupted estrous cycles
Figure 2. Estrous Cycles and vaginal smear. (A) At 8 weeks of age, estrous cycles were monitored continuously for 10 days. P: Proestrus Stage; E: Estrus Stage; M: Metestrus Stage; D: Diestrus Stage. (B) The representative H&E staining images of different estrous cycles. (Data presented as Mean±SD, n = 5 per group).
3. BKS-Lepr-/- and B6-Lep-/- exhibit abnormal ovarian structures
Figure 3. Tissue weight and ovary H&E staining. (A) Ovary weight and uterus weight at 12 and 16 weeks of age. (B) B6: Corpora lutea (CL) and follicles at various stages can be observed.
B6-Lep-/-: No corpora lutea, presence of cystic follicles (*, 7/11). BKS-Lepr-/-: No corpora lutea, a large number of atretic follicles (black arrow), and presence of cystic follicles (*, 1/5). (Data presented as Mean±SD, n = 5-11 per group, ***denoted p<0.001).
BKS-Lepr-/- mice show persistent diestrus, absence of a complete estrous cycle, and no corpora lutea in the ovaries, but with a large number of atretic follicles observed. B6-Lep-/- mice also exhibit persistent diestrus, absence of a complete estrous cycle, and no corpora lutea in the ovaries, with the presence of cystic follicles.