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P. G. MANTLE

Summary.

Pregnant mice fed on a diet containing agroclavine (250 μg/day) during the 2 to 3 days before nidation failed to implant but returned to oestrus within a few days. Eight weeks of agroclavine treatment did not impair the subsequent fertility of virgin mice. Female mice fed on the agroclavine diet conceived normally, and alkaloid treatment during the first 2 days of pregnancy or after implantation did not affect the pregnancy. Agroclavine did not affect pregnancy when injected subcutaneously. Ergotoxine, ergosine and lysergic acid α-hydroxyethylamide were also found to interrupt pregnancy when administered in the diet.

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C. A. FINN and P. G. MANTLE

The naturally occurring ergot alkaloid, agroclavine, interrupts pregnancy when administered to mated female mice in the diet at a non-toxic dosage for 2 to 3 days before implantation (Mantle, 1969). A similar action in the rat has also been reported (Edwardson & Macgregor, 1969), and the reversibility of the agroclavine implantation block by daily injections of progesterone suggests that the alkaloid may act either at the hypothalamic or ovarian level. The investigation reported here was conducted to determine the effect of the alkaloid on the cellular changes in the uterus which precede implantation in the mouse. During early pregnancy in the mouse, there is an abrupt change in the pattern of cell division in the uterus between the 3rd and 4th days after mating. On the 3rd day, large numbers of the epithelial cells
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P. G. MANTLE and C. A. FINN

Pregnancy in the rat can be prevented by a single intragastric administration of d-6-methyl-8-cyanomethylergoline (CME), a new synthetic ergoline derivative, during the first 7 days after mating (Režabek, Semonský & Kucharczyk, 1969). This substance is structurally closely related to the naturally occurring alkaloid, agroclavine, which has been shown to prevent implantation in mice and rats (Mantle, 1969; Edwardson & MacGregor, 1969).

In a preliminary experiment, following the technique (Režabek et al., 1969) successfully used in rats, CME (250 μg in 250 μl of 1 % tartaric acid) was administered to five mice by a single intragastric injection on each of the first 7 days of pregnancy. Eighteen out of thirty-five treated mice remained pregnant in comparison with twenty-three out of thirty-five untreated control mice. Thus, as there was no consistent evidence that implantation

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J. C. GREATOREX and P. G. MANTLE

Summary.

Milled ergot (Claviceps purpurea) sclerotia containing ergotamine (0·25%), alkaloid-free ergot and alkaloid-free ergot to which ergotamine tartrate had been added were administered to pregnant sheep, either orally or through a ruminal cannula. The daily dosage (administered as three sub-doses) of ergot sclerotia was 0·4 g/kg body weight and, where alkaloid was involved, ergotamine was presented at 1 mg/kg. The milled ergot, irrespective of route of administration, produced severe illness. In some ewes, there was also uterine involvement. By contrast, alkaloid-free ergot had no effect even when the daily dosage was increased by 50%. When ergotamine tartrate was added to the alkaloidfree ergot tissue, however, the mixture elicited a marked clinical response with abortions. Dosage of animals under field conditions during the 11th week of pregnancy gave either an immediate or a delayed response which resulted in acute illness in the ewe but did not affect pregnancy. Dosage of animals under loose box conditions at later stages in pregnancy resulted in less acute illness in the ewe but caused fetal death in three out of four animals at or beyond the 3½-month stage of pregnancy.