Active immunization of ewes against prostaglandin F2αto control ovarian function

The hypothesis that pregnancy success could be improved in early postpartumewes by prolonging the lifespan of the corpus luteum via active immunization against prostaglandin F2α(PGF2α) was tested. Further experiments in ewes immunized against PGF2αinvestigated the effects of exogenous PGF2αon the preovulatory follicle and the effects of PGF2αand oestradiol benzoate on corpus luteum function. Four weeks prepartum, 39 ewes bred to lamb during seasonal anoestrus received either 5 mg PGF2α–ovalbumin conjugate (n= 20; immunized) or ovalbumin (n= 19; control) in Freund's complete adjuvant. Treatments were repeated on day 5 post partumwith reagents emulsified in Freund's incomplete adjuvant. On day 17 post partum, ewes received 500 iu pregnant mares' serum gonadotrophin (PMSG) and 48 h later 50 μg gonadotrophin-releasing hormone (GnRH). Laparoscopy was performed 36 h after GnRH to assess ovarian activity and ewes with recent ovulations were inseminated into the uterus. No immunized ewes had ovulated, but ten had follicles that luteinized and secreted progesterone during the 8 weeks studied. Eighteen of 19 control ewes ovulated and 15 of 18 had increased progesterone concentration for at least 21 days. By day 70 post partum, progesterone had returned to basal values in all control ewes. In a second study, 24 immunized ewes bearing persistent corpora lutea, and for which the interval from the previous parturition was greater than 90 days, received 15 mg PGF2αand 500 iu PMSG followed 48 h later by 50 μg GnRH. PGF2αinduced corpus luteum regression in all ewes. PMSG and GnRH treatments resulted in oestrus in 21 of 24 ewes. Sixteen hours after GnRH, 10 ewes received a second injection of 15 mg PGF2α. PGF2αinduced follicular rupture in eight of ten immunized ewes, whereas only two of 14 ewes not receiving PGF2αovulated (P< 0.01). All anovular ewes had large cystic follicles that luteinized. In a third study, 22 ewes immunized against PGF2α, and having persistent corpora lutea, received, on two consecutive days, either oestradiol benzoate (750 μg; n= 11) in oil or oil (n= 11). Laparoscopy was performed on all ewes immediately before injections and four of the 11 ewes in each group possessed uterine horns that were filled with fluid. No fluid was judged to be in the horns of the remaining seven ewes in each group. On the basis of serum concentrations of progesterone and laparoscopies, oestradiol benzoate induced luteal regression in those ewes with uterine fluid and failed to induce luteal regression in those ewes lacking uterine fluid. Luteal function was unaffected in ewes that received the oil vehicle. These data suggest that premature luteal regression was not the reason for failure of occurrence of pregnancy. Immunization against PGF2αwas effective in blocking ovulation, but not in inhibiting oestrous behaviour or the formation of persistent luteal tissue. Treatment of immunized ewes with exogenous PGF2αrestored the ability of ewes to ovulate, providing further evidence for the involvement of PGF2αin ovulation. The ability of oestradiol to induce luteolysis in immunized ewes was associated with the presence of uterine fluid.