The pathophysiology underlying follicular cysts appears to be lack of an estradiol (E2)-induced GnRH/LH surge due to hypothalamic insensitivity to E2. In addition, progesterone (P4) can cause animals with follicular cysts to resume normal cyclicity and normal hypothalamic responsiveness to E2. We postulated that follicular cysts may be a pathological manifestation of a physiological state that cows, and possibly other species, go through during the normal estrous cycle but the rise in P4 following ovulation induces them back to normal hypothalamic responsiveness to E2. Based on this hypothesis, we expected that removal of the ovary containing the corpus hemorrhagicum would prevent the normal rise in P4 following ovulation and induce development of follicular cysts. Cows (n = 24) on day 7 of the estrous cycle were treated with prostaglandin F2agr; (PGF2agr;) and time of ovulation was detected by ovarian ultrasonography every 8 h. Immediately following detection of ovulation, cows were randomly but unequally assigned to have the ovary containing the corpus hemorrhagicum removed (TRT; n = 16) or the ovary opposite to the corpus hemorrhagicum removed (CON; n = 8). Cows were subsequently evaluated by daily ultrasound and blood sampling to determine follicular dynamics. Ovulation was detected at 93.7 ± 4.5 h after PGF2agr; injection. All CON cows had a normal estrous cycle length (22.0 ± 0.6 days) after ovariectomy (OVX). Half of the TRT cows became anovular (TRT-ANO; n = 8) after OVX with large anovular follicles developing on the ovary (maximal size, 25.4 ± 1.4 mm; range, 20–32 mm). However, eight TRT cows ovulated (TRT-OV; n = 8) 7.3 ± 0.6 days after OVX. Control cows had a normal P4 rise after ovulation. Removal of the newly formed corpus hemorrhagicum prevented the rise in circulating serum P4 in TRT-ANO cows throughout the 25-day experimental period. The TRT-OV cows had a delayed increase in circulating P4 but it was normal in relation to time of ovulation. Serum E2 concentrations were similar among groups (TRT-OV, TRT-ANO and CON cows) until 7 days after OVX. Serum E2 concentrations then decreased in TRT-OV and CON cows but remained elevated (>5 pg/ml) in TRT-ANO cows. Thus, the endogenous increase in circulating E2 that induces the GnRH/LH surge and estrus is sufficient to induce cows into a physiological state that resembles follicular cysts if it is not followed by increased circulating P4.
Ahmet Gümen and Milo C Wiltbank
Victor E Gomez-León, O J Ginther, Rafael R Domingues, José D Guimarães and Milo C Wiltbank
Previous research demonstrated that acute treatment with GnRH antagonist, Acyline, allowed follicle growth until ~8.5 mm and no dominant follicle was selected. This study evaluated whether deficient LH was the underlying mechanism for Acyline effects by replacing LH action, using human chorionic gonadotropin (hCG), during Acyline treatment. Holstein heifers (n = 24) during first follicular wave were evaluated by ultrasound and randomized into one of three treatments: Control (saline treatments), Acyline (5 µg/kg Acyline), or Acyline+hCG (Acyline plus 50 IU of hCG at start then 100 IU every 12 h). Pulses of LH were present in Control heifers (9 Pulses/10 h) but not during Acyline treatment. Data were normalized to the transition to diameter deviation (day 0; F1 ~7.5 mm). Diameter deviation of the largest (F1) and the second largest (F2) follicle was not observed in Acyline-treated heifers, whereas control heifers had decreased growth of F2 at F1 ~7.5 mm, indicating deviation. Selection of a single dominant follicle was restored by providing LH activity in Acyline+hCG heifers, as evidenced by F1 and F2 deviation, continued growth of F1, and elevated circulating estradiol. Separation of F1 and F2 occurred 12 h (~7.0 mm) earlier in Acyline+hCG heifers than Controls. Circulating FSH was greater in Acyline than Controls, but lower in Acyline+hCG than Controls after day 1.5. In conclusion, dominant follicle selection and growth after follicle deviation is due to LH action as shown by inhibition of this process during ablation of GnRH-stimulated LH pulses with Acyline and restoration of it after replacement of LH action by hCG treatment.