320 BASELINE AND SUPEROVULATION HYPERANDROGENISM AND FOLLICULAR DYNAMICS IN THE OSSABAW PIG SUGGEST AN ANIMAL MODEL FOR POLYCYSTIC OVARY SYNDROME

Abstract

The objective of this study was to validate the obese Ossabaw pig as a model of the obese polycystic ovary syndrome (PCOS) phenotype. Four sows were fed a high fat–high fructose diet to induce metabolic syndrome (MetS), and 5 sows were fed a control diet (Lean). Sows had twice-weekly blood collection and ovarian ultrasound; serum was assessed weekly for androstenedione (A) and twice weekly for progesterone (P). The follicular phase of the oestrous cycle was determined by absence of a corpus luteum on ultrasound and a nadir in P below 2.5 ng mL^–1. After baseline measurement collection, sows were down-regulated with a GnRH agonist and superovulated with subcutaneous FSH/LH injections administered every 8 h until large follicles (5–12.5 mm) were visible on the ultrasound (3–7 days), at which point hCG was administered. Oestrous cycle data were divided into follicular (F), early luteal (EL), mid-luteal (ML), late luteal (LL), and transition (T) phases. Superovulation data were subdivided by percentage of stimulation completion and number of days post-hCG. Non-normal data were transformed before analysis with PROC MIXED for repeated-measures in SAS. The MetS sows had a longer average oestrous cycle length than did Lean sows (MetS, 32.2 ± 1.3 days; Lean, 25.2 ± 1.0 days; P < 0.05). In each cycle phase, with the exception of T, MetS A (F: 1.95 ± 0.01 ng mL^–1, EL: 1.31 ± 0.07 ng mL^–1, ML: 1.14 ± 0.04 ng mL^–1, LL: 1.34 ± 0.04 ng mL^–1) was higher (P < 0.05) than Lean A (F: 1.11 ± 0.09 ng mL^–1, EL: 0.98 ± 0.07 ng mL^–1, ML: 0.98 ± 0.04 ng mL^–1, LL: 1.04 ± 0.04 ng mL^–1). Within the MetS sows, A was significantly higher in F compared with the entire luteal (L) phase (1.25 ± 0.05 ng mL^–1; P < 0.05). The MetS sows had similar numbers of large follicles in the F (3.0 ± 1.1 avg pig^–1) and L (3.6 ± 1.1 avg pig^–1) phases, whereas Lean sows had fewer large follicles during L (0.7 ± 1.1 avg pig^–1) compared with F (3.0 ± 1.1 avg pig^–1) phase (P < 0.05). The MetS sows had more large follicles than did Lean sows during the EL (MetS, 7.0 ± 1.1, Lean, 0.0 ± 0.0; P < 0.05) and T phases (MetS, 4.0 ± 1.1; Lean, 1.0 ± 1.1; P < 0.05). Lean sows did not form any cystic structures (CS; >12.5 mm). The MetS sows had significantly more CS than did Lean sows during the EL and ML phases (2.0 ± 0.5 avg pig^–1; P < 0.05). In response to superovulation, MetS sows had higher A than did Lean sows at completion of stimulation (MetS, 8.45 ± 1.75 ng mL^–1; Lean, 2.79 ± 1.36 ng mL^–1; P < 0.05) and tended to have higher A than did Lean sows one day post-hCG administration (MetS, 6.00 ± 1.75 ng mL^–1; Lean, 2.53 ± 1.36 ng mL^–1; P = 0.09). Although not significantly different, MetS sows produced higher numbers of large follicles (range: 9.0–58.6 avg pig^–1) than did Lean sows (range: 6.3–33.3 avg pig^–1). In conclusion, MetS sows have long oestrous cycles, are hyperandrogenemic, have increased numbers of large follicles in the luteal phase, form cystic structures, and may recruit abnormally high numbers of large follicles in response to superovulation. The obese Ossabaw sow is an excellent animal model in which to study PCOS because women with this disease similarly have oligomenorrhea, hyperandrogenism and ovarian cysts, and recruit high numbers of large follicles at superovulation.