The PGF2α agonists luprostiol and d-cloprostenol reliably induce luteolysis in luteal phase mares without evoking clinical side effects or a stress response

• We evaluated the stress response to PGF2α analogs in luteal phase mares.
• Luprostiol and d-cloprostenol injection increased cortisol release.
• No other signs of physiological stress response occurred.
• Luteal function after estrous induction was not impaired.

In the present study we have evaluated a possible stress reaction in response to two different PGF2α analogs—luprostiol and d-cloprostenol—and their effects on estrous cycle characteristics. In a cross-over-design eight mares received in alternating order either luprostiol (Treatment LUP; 3.75 mg im), d-cloprostenol (Treatment CLO; 22.5 μg im) or saline (Treatment CON; NaCl 0.9% 0.5 ml im) on day 8 after ovulation. Injection of either LUP or CLO, but not of CON resulted in a significant decline of progesterone concentration in plasma to baseline concentrations within two days (time: p < 0.001, treatment: p < 0.01, time × treatment: p < 0.05). The treatment to ovulation interval was significantly shorter in LUP and CLO than in CON cycles (LUP: 9.4 ± 0.4 d; CLO: 9.4 ± 1.3 d; CON: 16.1 ± 0.8 d; p < 0.001). Injection of either LUP or CLO, but not of CON significantly increased salivary cortisol concentration (immediately before injection: CON 1.3 ± 0.2, LUP 1.4 ± 0.3, CLO 1.4 ± 0.3 ng/ml; 60 min after injection: CON 1.0 ± 0.3, LUP 8.0 ± 1.4, CLO 4.2 ± 0.7 ng/ml; time: p < 0.01, treatment: p < 0.001, time × treatment: p < 0.001). Heart rate decreased over time (p < 0.05) independent of treatment and no changes in heart rate variability were detected. Injection of the PGF2α analogs CLO and LUP reliably induced luteolysis and apart from a transient increase in salivary cortisol concentration no signs of a physiological stress response or apparent side effects occurred.