Low concentrations of zearalenone in diets of mature gilts.

Four groups of sixteen gilts were each individually fed diets containing 0, 3, 6 or 9 ppm pure zearalenone starting the day after they exhibited puberal estrus. They were artificially inseminated twice at subsequent heat periods. Fifteen of the 30 gilts not exhibiting estrus within 80 d of the start of the experiment were slaughtered and their reproductive tracts examined. The remaining 15 gilts that did not return to estrus were fed the control diet after 80 d to determine the effect on return to estrus. Eighty-eight percent of the gilts fed 6 or 9 ppm zearalenone became pseudopregnant as confirmed by plasma progesterone levels and(or) examination of their reproductive tracts. However, three animals fed the two higher levels of zearalenone conceived and farrowed. No conclusions can be made regarding the effect of zearalenone on litter size due to the relatively few numbers of gilts fed the higher levels of zearalenone that farrowed. Gilts fed diets containing 6 or 9 ppm zearalenone returned to estrus spontaneously (n = 7) or following injection of cloprostenol (n = 8) approximately 45 d after the removal of zearalenone from their diet.

Dopamine blockade reverses the inhibition of prolactin which results from intrahypothalamic pituitary grafts.

When mated with fertile bucks, rats with anterior pituitary (AP) tissue grafted into the hypothalamus did not exhibit prolongation of the diestrous cycle. Treatment of these rats with alpha-methyl-p-tyrosine, reserpine, or haloperidol for 1 or 2 days after mating increased the interestrous interval by a few days in all rats and to more than 8 days (leading to pseudopregnancy or pregnancy) in 20% of the cases. The same treatment in unmated normals resulted in 80% becoming pseudopregnant. To get more than 70% of rats with hypothalamic AP grafts pregnant or pseudopregnant required dopamine-blocking drugs for 3 or 4 consecutive days. Pregnancy was prolonged in 50% and lactation was impaired in 78% of the grafted rats which littered. Both impairments, like the original failure of the luteotrophic response, are attributed to the effects of PRL autofeedback from the hypothalamic AP grafts. These experiments provide further evidence that the mechanism whereby PRL in the hypothalamus inhibits PRL secretion involves elevation of dopamine.

Effects of opiate antagonists on early pregnancy and pseudopregnancy in mice.

Administration of naltrexone or the long-acting morphine antagonist chlornaltrexamine before infertile mating had no effect on the length of the resulting pseudopregnancy in mice. Naltrexone in doses of 10 to 200 mg/kg s.c. given on Days 2 or 3 of pregnancy showed no consistent effects on the maintenance of pregnancy. Multiple doses or intracerebroventricular administration of naltrexone also had no effect. Chronic infusion of naltrexone, provided by mini-osmotic pumps, from Day 1 of pregnancy had no effect on the incidence of pregnancy or the number of embryos implanted. These results suggest that endogenous opioids do not play a critical role in this prolactin-dependent physiological process.

Delayed pseudopregnancy in the mouse.

Treatment of female mice with bromocriptine on Day 1 or 3 of pregnancy induced many of the females to return to oestrus. The incidence of extended cycles (7--10 days) and pseudopregnancies following this return to oestrus was significantly higher than in unmated control females. These observations are consistent with the existence of a 'mnemonic' component of the luteotrophic system in the mouse.

Maintenance of pseudopregnancy by prolactin in indomethacin treated rats.

1. The effects of bromocriptine and indomethacin on prolactin-induced pseudopregnancy were studied in pituitary grafted rats. 2.Administration of bromocriptine (a prolactin suppressant drug) at a total dose of 3 mg/kg body weight, given in 3 divided doses on day 5 of pseudopregnancy, effectively terminated it within 3 days. However, injection of indomethacin (a prostaglandin inhibitor) at a total dose of 6 mg/kg body weight, given in 3 divided doses, on the same day of pseudopregnancy had no significant effect on its duration. 3. It appears unlikely that the luteotrophic effect of prolactin on the corpus luteum is mediated by the stimulation of prostaglandin synthesis.

Indomethacin and uterine evacuation of conceptus in rats: possible mode of action.

Indomethacin at a dose of 2.5 mg/kg from day 18 through day 20 of pregnancy was found to extend the duration of gestation for 2-3 days over the control value. Conversely, prostaglandin F2 alpha (PGF2 alpha) at a dose of 2.0 mg/kg on day 18 of pregnancy induced premature parturition. PGF2 alpha given concurrently with indomethacin resulted in neutralisation of the drug action and the animals delivered viable pups as identically recorded in controls. Failure of indomethacin to extend the length of pseudopregnancy in either bilaterally hysterectomized or bilaterally decidualized pseudopregnant rats revealed that the lengthening of the duration of pregnancy caused by indomethacin is not due to an extension of luteal span, but results from relaxation of the uterine smooth musculature.

Pregnancy blockage and the memory of the stud male in the vole (Microtus agrestis).

When female voles were allowed contact with the stud male for only 1 h at the time of mating, 55% exhibited pregnancy failure when exposed to a strange male 48 h later. When females were made psuedopregnant by hormone treatment and vaginal stimulation (i.e. no stud male involved), 87% exhibited luteal failure when exposed to a strange male. It is suggested that the characteristics of the stud male are rapidly imprinted upon the female at the time of mating and that this imprinting is important in preventing the female showing a blocking response to this male upon any subsequent exposure.

Termination of pseudopregnancy in rats by silastic-PVP-PGF2 alpha tube.

The efficacy of a one-end or both-end open Silastic-polyvinyl-pyrrolidone (Silastic-PVP) tube containing 600 microgram prostaglandin-F2 alpha (PGF2 alpha) and placed subcutaneously on day-6 of pseudopregnancy (PSP) in the induction of premature termination of PSP was compared. A both-end open Silastic-PVP-PGF2 alpha tube was more efficacious in inducing an early termination of PSP with a mean duration of 7.8 days. By contrast, PSP females receiving a one-end open Silastic-PVP-PGF2 alpha tube showed a mean duration of PSP of 9.9 days. The shortened duration of PSP in both these treatment groups was significantly different from the control value of 13.1 days. The significant drop in progesterone (delta 4P) but rise in 20 alpha-dihydroprogesterone (20 alpha-DHP) occurred 24 hr after treatment in PSP rats treated with both-end open Silastic-PVP-PGF2 alpha tube, whereas similar changes in delta 4P and 20 alpha-DHP took place 48-72 hr after the deposition of a one-end open Silastic-PVP PGF2 alpha tube. It is concluded than an initial larger amount of circulating PGF2 alpha is needed to induce an early premature termination of PSP. The exposure of corpus luteum to a more sustained but lower level of PGF2 alpha leads to a slower response.

RMI 12,936 and pseudopregnancy in rats.

RMI 12,936, when injected subcutaneously at a dose of 2 mg, either on Day 6 of psuedopregnancy (PSP-6) or on PSP-6,7 and 8, shortened the duration of PSP from 12.3 +/- 0.3 (control) to 8.3 +/- 0.1 or 8.7 +/- 0.2 days, respectively. During PSP, plasma progesterone (delta 4P) levels in the peripheral plasma showed a trend of decrease by PSP-9 (52.0 +/- 4.6 on PSP-8 to 42.3 +/- 3.1 ng/ml on PSP-9). Administration of RMI 12,936 on PSP-6 resulted in a significant decrease in delta 4P and pregnenolone (delta 5P) within 24 hr after treatment but caused no apparent changes in 20 alpha-dihydroprogesterone (20 alpha-DHP) levels. However, a significant decrease of delta 4P/20 alpha DHP ratio was encountered 24 hr after RMI 12,936 treatment. The persistent occurrence of proestrous smear after PSP termination, but absence of estrous vaginal cytology, might be attributed to the slight estrogenicity of RMI 12,936. After the premature termination of pseudopregnancy induced by RMI 12,936, the female rats were sexually receptive for at least 3 weeks but failed to conceive, suggesting that this compound has a prolonged contraceptive effect.

Interruption of pregnancy in rats by azastene, an inhibitor of ovarian and adrenal steroidogenesis.

Azastene (4,4,17alpha-trimethylandrost-5-eno[2,3-d]isoxazol-17-ol), when given orally to rats at a dose of 12 mg/kg once on day 10 of pregnancy, induced resorption of all fetuses and a precipitous decline of circulating progesterone levels in all test animals. The disruption of pregnancy was prevented by a single, concurrent, subcutaneous injection of progesterone (4 mg/rat). Thus, the interruption of pregnancy occurs via an acute, short-term, reversible progesterone withdrawal. The reduction of progesterone levels is brought about by competitive inhibition of ovarian 3beta-hydroxysteroid dehydrogenase activity. Despite its potency as an interceptive agent, azastene exhibited only moderate endocrine-related effects if given daily for 2 weeks to female rats at doses as high as 1000 mg/kg. Those effects were an increase in the number of vaginal estrous days and a dose-related increase in adrenal weight. The latter effect is consistent with the known adrenal inhibitory properties of this drug.