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Pituitary and ovarian function in ewes immunized against the amino-terminal peptide (N) of the inhibin ₄₃-subunit

Immunization of ewes against the amino-terminal peptide (N) of the pro--subunit of inhibin has been shown to reduce fertility, thought to be due to disruption of ovulation. The aims of this study were to examine the effects of active immunization of ewes against N on circulating concentrations of FSH, LH and on ovarian inhibin and progesterone, and to relate these observations to number of corpora lutea and oocyte recovery rates. Ewes were immunized against one or both of two recombinant full length bovine-N immunogens (FP₁ and FP₂). Three experiments were performed in which jugular venous plasma was sampled from control and immunized ewes: (1) hourly across the oestrous surge of gonadotrophins (Expt 1); (2) daily for one entire oestrous cycle, and in the subsequent cycle, oviducts were flushed to recover ovulated eggs (Expt 2); and (3) samples were taken at 10 min intervals during the follicular and luteal phases (Expt 3). Binding of ¹²⁵I-labelled N_1–26 to serum was greater (P < 0.05) in immunized groups than in controls for all experiments. The number of eggs per corpus luteum recovered from the oviducts was lower (P < 0.05) in the N-immunized groups (39%) than in controls (88%). There were more (P < 0.05) corpora lutea per ewe in FP₂ immunized groups 4 (1.8 ± 0.45) and 5 (1.75 ± 0.5) than in the control group (1.13 ± 0.13), but no increase in group 3 (FP₁; 1.4 ± 0.24). The oestrous surge of LH, basal values across cycle and the frequency of LH pulses were similar in treated and control groups. Circulating FSH concentrations were higher (P < 0.05) than those of controls in all immunized groups that had binding greater than 10% at all stages of the cycle, except during the oestrous surge. A corresponding decrease (P < 0.05) in circulating inhibin concentrations was observed in most immunized groups, with a significant negative correlation between inhibin values and N-binding in the follicular phase of the cycle. The pattern of progesterone production during the cycle was similar, with a slight non-significant increase in immunized compared with control ewes. These data confirm the previous observation that ovulation is impaired in ewes immunized against the amino-terminal peptide of inhibin ₄₃ and also suggest that the mechanism of this effect does not involve disruption of pituitary function, implying a role for N in the intraovarian events of ovulation.