Use of fluorogestone acetate after breeding to reduce the effect of premature luteal regression in dairy goats when superovulation is induced with FSH

The aim of the present study was to determine the effect of fluorogestone acetate (FGA) administered after mating, on embryo production in the dairy goat subjected to conventional superovulatory and embryo recovery protocols. Adult does, most of them of the French Alpine breed, were randomly assigned after a FSH-superovulatory estrus and fertile matings to a control group (n=20) or to a treated group (n=20) in which intravaginal sponges impregnated with FGA were inserted after mating and remove before embryo collection (day 6). Blood samples were collected every 12h from days 1 to 7 post-estrus and serum progesterone concentrations were determined. The FGA-group had a lesser percentage of does with normal corpora lutea (CL) and a greater percentage of animals with CL in regression or mixed (normal and in regression) when compared with the control group (13.3 and 64.7%, 53.3 and 23.5%, and 33.3 and 11.8%, respectively; P<0.05). Mean number of normal CL per doe was less and mean number of regressed CL greater in FGA as compared with the control group (4.2 compared with 10.7 and 8.5 compared with 3.6, respectively; P<0.05). There were no differences (P>0.05) in recovery rate, total number of CL, total recovered structures, oocytes and transferable and non-transferable embryos between groups. Serum progesterone concentrations from day 5 to 7 post-estrus were lower (P<0.05) in FGA as compared with the control group. Percentage of does with luteal failure on day 6 post-estrus was greater in FGA as compared with the control group (86.6 compared with 33.3%; P<0.01). When considering only does with luteal failure on day 6 post-estrus, mean total recovered structures, transferable embryos and percentage of does rendering > or =3 transferable embryos were greater in the FGA compared with the control group (6.3 and 1.3 structures, 4.5 and 1.2 embryos, 67 and 17%, respectively; P<0.05). In does not having luteal failure, FGA administration did not appear to affect embryo production or embryo survival. These results indicate that FGA administration after mating improves embryo recovery in dairy goats with luteal failure after superovulatory treatment. However, it also increases the incidence of luteal regression when administered early in the estrous cycle.     

The effects of oral micronized progesterone on smoked cocaine self-administration in women

There are currently no FDA-approved pharmacotherapies for cocaine abuse. Converging preclinical and clinical evidence indicates that progesterone may have potential as a treatment for cocaine-abusing women, who represent a growing portion of cocaine users. We have previously shown that oral progesterone reduced the positive subjective effects of cocaine in female cocaine users during the follicular phase of the menstrual cycle, when endogenous progesterone levels were low. To extend these findings, the present study assessed the effects of oral progesterone (150 mg BID) administered during the follicular phase on smoked cocaine self-administration in women relative to the normal follicular and luteal phases. Healthy, non-treatment seeking female cocaine smokers (N = 10) underwent three 4-day inpatient stays, during: 1) a normal follicular phase; 2) a normal luteal phase; and 3) a follicular phase when oral progesterone was administered. During each stay, participants completed 4 self-administration sessions in which they first smoked a “sample” dose of cocaine (0, 12, 25 or 50 mg) and then had 5 opportunities at 14-minute intervals to self-administer that dose at a cost of $5 per dose. Expected cocaine dose effects on self-administration, subjective effects, and cardiovascular effects were observed. However, there was no effect of oral progesterone administration or menstrual cycle phase on cocaine self-administration. Thus, oral progesterone was not effective in reducing cocaine use in women under the current conditions. However, based on previous literature, further research assessing the role of oral progesterone for the treatment of cocaine dependence in women is warranted.     

Reproductive performance of Coopworth ewes following oral doses of zearalenone before and after mating

The reproductive performance of Coopworth ewes after administration of zearalenone was determined in two trials. In Trial I, zearalenone was administered to groups of 33 ewes at rates of 0, 1.5, 3.0, 6.0, 12.0 and 24.0 mg/ewe/day for 10 days, starting on Day 7 of the oestrous cycle before mating. There was a linear decline (P less than 0.001) in ovulation rate with dose of zearalenone; also cycle length decreased and duration of oestrous increased with increasing dose levels. Reductions in the incidence of ovulation and in fertilization were seen only at doses of 12 and 24 mg. In Trial 2, groups of 50 ewes were given the same range of doses of zearalenone for 10 days, starting 5 days after mating to entire rams. There was no effect of zearalenone treatment after mating on pregnancy rate or embryonic loss. These results indicate that the effects of zearalenone, administered orally, on ewe reproduction, at the dose levels examined, were restricted to ewes exposed before mating. Intakes of zearalenone of 3 mg/ewe/day or more during this period would be reflected as depressed ovulation rates and lower lambing percentages.     

Effects of selenium toxicity on oestrous cyclicity, ovarian follicles, ovulation and foetal survival in rats

Effects of intraperitoneal injections of sodium selenite (2.0 and 4.0 mg/kg body weight) to normally cycling female albino Wistar rats daily for 30 days, and of single injection either during proestrous or oestrous and at each stage of the 4-day oestrous cycle were determined on oestrous cyclicity, ovarian follicles, ovulation, implantation and pregnancy outcome on day 14 of gestation. Administration of selenite for 30 days had no effect on the duration of first two oestrous cycles but afterwards the rats remained at the dioestrus stage. Their ovaries developed cystic follicles. Selenite treatments during the oestrous cycle preceding mating affects the implantation and pregnancy outcome in a dose-related manner. Its single dose containing 2.0 mg/kg body weight administered either at proestrous or oestrous, though had no effect on different reproductive parameters investigated in this study but its daily dose during the 4 day oestrous cycle reduced the number of corpora lutea and implantations as compared to saline injected control female rats. Similar effects of a single dose of selenite (4.0 mg/kg body weight) when injected at proestrous were recorded. Higher dose of selenite at oestrous or throughout the cycle decreased the number of implantations, but in addition, also increased the resorption rate/litter on day 14 of gestation. The present studies clearly show that high selenium levels in the body during the oestrous cycle preceding mating affects the number of ovulations, implantations and live embryos depending upon its dose and stage of administration.     

Factors affecting the yield of viable embryos by superovulated Holstein-Friesian cows

GnRH treatment (250 ug) 48 h after prostaglandin F(2alpha) in 40 superovulated cows induced a release of LH (increment > 5 ng/ml) in only 13 of the older cows. Eleven of these cows did not yield viable embryos. Thirty-two of 75 cows had preovulatory surge levels of LH 48 h after prostaglandin treatment. Plasma progesterone concentrations were determined in 140 cows at the time that superovulation was initiated. Eighty-four of these donors were superovulated with 40 mg of FSH and 56 donors with 48 mg of FSH. There was no relationship (P > 0.05) between the concentration of progesterone at the start of superovulation with either ovulation rate determined by palpation per rectum or the number of viable embryos per flush. These parameters were also unaffected (P > 0.05) by age of the donor or the dose of FSH. In another group of donors, treatment with 40 mg FSH was compared over a 3-d (n = 28) and a 4-d (n = 18) interval. The donors treated with FSH over a 3-d period had similar ovulation rates but yielded less viable embryos (1.5 v 5.8, P < 0.05). The fertility rate of 33 cows, inseminated 60 and 72 h after prostaglandin, was comparable to the fertility rate of 18 cows inseminated at 60, 72 and 84 h after prostaglandin treatment.     

Effect of RMI 12,936, an antiprogestational steroid on decidual cell reaction and embryos in rat.

Subcutaneous administration of RMI 12,936 at a dose level of 2 mg/rat on day 5 of unilaterally pregnant rat having trauma-induced decidual cell reaction (DCR) in the contralateral uterine horn, suppresses DCR, induces resorption of implanted embryos and leads to decrease in the plasma level of progesterone. Progesterone replacement (D 5-8) in this situation reverses DCR suppressive effect of RMI 12,936 but fails to prevent resorption of implanted embryos. It is concluded that possibly the drug simultaneously exerts embryotoxic as well as luteolytic effects, but these effects are independent.     

Induction of luteal activity and progesterone secretion in the nonpregnant one-humped camel (Camelus dromedarius)

Corpora lutea (n = 20) were detected in 5 one-humped female camels studied during a period of 4 months. Complete mating by a vasectomized male, male introduction into the pen of females without mating, or a progesterone decrease from a previous corpus luteum were followed by a similar progesterone pattern. A maximal plasma concentration of 4.5 +/- 1.5 ng progesterone/ml (2.7-8.8 ng/ml) occurred 8.55 +/- 1.32 days (6-11 days) after the inducing stimulus. Luteal regression, beginning 8.65 +/- 1.18 days after the stimulus, was completed at Day 11.55 +/- 1.05. Morphological development of ovarian structures, detected by rectal palpation, was in synchrony with the progesterone increase, but there was a prolonged period of regression. Females accepted mating up to 7 days after the ovulatory stimulus, when progesterone levels were as high as 3.5 ng/ml. This study establishes the absence of pseudopregnancy in the one-humped female camel, and offers opportunities for improving the management of reproduction. It also shows that ovulatory stimuli other than mating can be effective in these animals.     

Effects of clomiphene citrate on early pregnancy in guinea-pigs

Clomiphene citrate (2 mg/kg body wt) given on the day of mating can block or interrupt pregnancy in guinea-pigs. Corpus luteum function, uterine histology, implantation and embryo development were studied in clomiphene-treated and control animals on Days 5, 9 and 20 of pregnancy. Following treatment, only 25% of the females were regularly pregnant, presenting large and healthy foetuses. The other females examined showed either pregnancy with embryos undergoing resorption or no sign of pregnancy. In these females, corpus luteum size was reduced, progesterone concentrations were very low and the endometrial glands and the epithelium were often altered. It is concluded that clomiphene causes a reduction in fertility by altering the uterus and, by directly or indirectly inducing luteolysis, causes later pregnancy loss.     

Effect of progesterone and medroxyprogesterone acetate on pregnancy length and litter size in mink

The objective of these studies was to determine the effect of progesterone and medroxyprogesterone injected at varying times post coitum on gestation length and litter size. During a 3-year period mink females of "Standard" strain were given progesterone at a dose 5 mg at 15 and 20 days in the first year and at 17-20 days in the second year, after the last mating. The respective control groups were given the vehicle. Medroxyprogesterone acetate was given in the second year at a dose of 4 mg at 14-19 days following the last mating and in the third year at a dose of 2 mg at 8 days after the last mating. The results on pregnancy length and litter size after progesterone injections in the experimental and respective control groups were as follows: 52.7 days and 4.3 kits, 51.3 days and 4.3 kits, 52.2 days and 5.8 kits, 50.2 days and 4.8 kits, 44.7 days and 5.6 kits, 46.0 days and 6.1 kits. A dose of 4 mg MPA resulted in the blockage of parturition in pregnant females. After administration of MPA at doses of 2 mg at 8 days following the last mating, the pregnancy length and litter size in the experimental group were: 48.0 days and 6.1 kits and in the control: 52.2 days and 4.8 kits.     

Prevention of tilorone developmental toxicity with progesterone.

The immunomodulator tilorone hydrochloride was administered (gastric intubation) once to time-pregnant Upj:TUC(SD)spf (Sprague-Dawley) rats in four experiments. In experiment 1, tilorone (250 or 500 mg/kg) was administered on day 10 of gestation. The dams were killed 4 or 72 hr after dosing. Interferon-like activity and drug levels were determined in maternal blood, spleen, and thymus, as well as in the embryos. In experiment 2, the test groups received progesterone (2 mg/kg), or tilorone (200 or 400 mg/kg), or progesterone and tilorone. The dams from each group were killed 24 or 48 hr after receiving tilorone. Experiment 3 was similar to experiment 2, except that the dams were killed on gestation day 20. In experiment 4, tilorone (400 mg/kg) was administered on gestation day 17, 18, or 19, and the dams were killed 24 hr after dosing or on gestation day 20. In all four experiments, tilorone-related maternal toxicity (regardless of whether progesterone also was administered) was observed, as characterized by marked decreases in weight gain, the occurrence of clinical signs, and in experiment 1 by decreased thymus weights, 72 hr post-dosing. Dose-related increases in the mean number of dead embryos and in serum interferon titers occurred 72 hr postdosing. In experiment 2, there was an increase in the number of dams in the 400-mg/kg (tilorone only) group with dead embryos only, 24 hr postdosing; similar results occurred in both the 200- and 400-mg/kg groups, 48 hr postdosing. However, in the groups that also received progesterone, a partial prevention of such embryolethality was evident. In experiment 3, embryotoxicity again was observed in both tilorone-treated groups, whereas several of the dams that were also given progesterone through day 19 of gestation experienced at least a partial prevention of the embryolethal effects of tilorone. In experiment 4, no fetotoxicity was observed despite the severe maternal toxicity evident.     

Metabolic,Hormonal, and Vascular Changes after Synthetic Oestrogen Therapy in Oophorectomized Women

Mestranol, the three-methyl ether form of ethinyloestradiol and one of the two oestrogens used in oral contraceptive steroids, was administered in a dose of 0·02 mg daily for 120 days to 25 oophorectomized women.Urinary oestriol and pregnanediol excretions were unaffected by the mestranol treatment but there was a shift of the maturation index of the vaginal smear to the right, indicating a correction of the pretreatment oestrogen deficiency. No significant change in the blood pressure or electrocardiograph recordings occurred during this relatively short period of administration. A significant rise in the serum protein-bound iodine, which might be regarded as an undesirable effect of mestranol on a long-term basis, occurred. Hepatic function as measured by bromsulphthalein was not impaired by the treatment. Mestranol had no effect on the total body water or on the total exchangeable potassium of the women. Its two most serious adverse effects were impairment of glucose tolerance and a high incidence (16%) of venous thrombo-embolic disease.The gravity of the adverse effects far outweighs any beneficial ones and precludes the use of mestranol alone for long-term hormone replacement therapy in postmenopausal women.     

Effect of indomethacin on egg transport and pregnancy in the rabbit.

Treatment of rabbits with indomethacin (10 mg/kg/day) 48 hr before mating, and with 20 mg/kg at 12 hr followed by 8 mg/kg at 48, 72 or 96 hr after mating did not affect the rate of egg transport through the oviduct. Indomethacin treatment at the time of implantation interfered with pregnancy and caused degeneration and resorption of embryos. These results suggest that inhibition of prostaglandin synthesis does not directly affect egg transport, but that prostaglandin appears to be required for the retention of implanted embryos.     

Abortifacient and endocrine effects of metergoline in beagle bitches during the second half of gestation

The purpose of this study was to investigate the abortifacient effects of high doses of metergoline when administered to pregnant beagle bitches during the second half of gestation and to define the endocrine effects of this treatment as represented by plasma progesterone and estradiol concentrations. Previously, metergoline had been shown to be incompletely luteolytic and induced abortion in only one of eight pregnant bitches when 0.4-0.5 mg/kg were administered twice daily for 5 days from Days 18 to 20 of diestrus. Nine pregnancies in six beagle bitches were used for the present study. Three bitches were treated in each of two consecutive pregnant cycles. Metergoline was administered at a dose of 0.6 mg/kg per os twice daily, starting on Day 28 after the cytological onset of diestrus. Abortion was induced in eight of the nine treated pregnancies and started after 3-23 days of treatment (mean 12.5 days, S.D. 6.4 days). The abortions were completed within 0.5-8 days (mean 2.2 days, S.D. 2.7 days). There were no side effects associated with metergoline treatment and none of the abortions was associated with complications that required intervention. In the single bitch that did not abort, an ovarian granulosa cell tumor was discovered when the single fetus had to be removed surgically at term. Plasma progesterone concentrations declined after the start of metergoline administration in all pregnancies but levels below 4.8 nmol/l were required for successful abortions. Plasma estradiol concentrations showed a tendency to decline and fluctuate concurrently with the plasma progesterone levels. However, suppression of plasma estradiol concentrations by metergoline was not as complete as the suppression of progesterone and did not seem a prerequisite for abortion. The hormone profiles and treatment period required for abortion tended to be similar for both cycles of the three bitches that were treated during two consecutive pregnancies. This suggests a bitch effect on the factors that determine the efficacy of metergoline to induce abortion. The large variation and length of the treatment period that was required until abortion commenced was probably related to the relatively early start of treatment compared to other studies. The results of this investigation suggest that, similar to other prolactin suppressing ergot derivatives, metergoline causes complete luteolysis and can be used to reliably induce abortion only during the last 3 weeks of gestation.     

Using hormone-treated pregnant cows as a potential source of oocytes for in vitro fertilization

In vivo collection of oocytes during pregnancy may be alternative method of obtaining gametes for in vitro fertilization (IVF) from genetically superior gestating cattle. The objectives of this experiment were to induce follicular growth in mature beef cows during each trimester of pregnancy, and then to collect oocytes and verify oocyte competency by IVF and subsequent embryo culture in vitro. Cyclic beef cows in Treatment A and pregnant cows in Treatment B were administered a total dose of 40 mg of FSH in descending dose levels (6, 5, 4, 3 and 2 mg) twice daily for 5 consecutive days. Cows in Treatment A were administered 25 mg of PGF(2)alpha and in Treatment B an equal volume of 0.9% saline at the seventh FSH injection. Pregnant cows in Treatment C were administered neither FSH nor PGF(2)alpha and served as a control group. Following a gonadotropin treatment, the ovaries of each female were evaluated for follicular development by ultrasonography. Oocytes were collected by follicle aspiration from cows in the first trimester. Following IVF procedures, the embryos were co-cultured on caprine oviductal cells, or in the chicken embryo co-culture system, or were placed in goat oviducts in vivo. The mean number of follicles per ovary 12 hours after FSH treatment was not different for cows in Treatments A and B, (8.1 vs 7.7) and both numbers were greater (P<0.05) than the 1.1 follicles per ovary for the control cows in Treatment C. Oocytes collected in vivo and exposed to IVF, resulted in 20% cleaving, and of these embryos 50% developed to the morula stage in culture. In summary, stimulating supplemental follicular development with FSH treatment during pregnancy and collecting the oocytes for IVF may be an alternative method for obtaining supplemental gametes from valuable donor cattle.     

Invitro uptake of estradiol and progesterone in the hamster uterus relative to the time of embryo transfer and stage of development

The normal time for cleavage to the 2- and 8-cell stages of development of naturally ovulated hamster embryos is 25–27.5 and 59–61 h respectively, after ovulation and mating. The corresponding values for PMS-hCG treated hamsters were 33–35.5 and 62–64 h respectively. When 2-cell embryos, obtained by this timing method, were transferred to the oviductal bursa on Day 2 of the cycle, and when 8-cell embryos were transferred to the uterus on Day 3 of the cycle, implantation rates of 61.5 and 64.0% respectively, were obtained. The current study was conducted to determine the effects of transfer on estradiol and progesterone uptake by the uterine tissue on Day 14 after mating. A 2-fold increase in estradiol uptake was observed in superovulated, nonpregnant uteri when compared with nonsuperovulated animals. This level was also significantly higher than with nonsuperovulated pregnant animals and of animals receiving 2-cell embryo transfers. Estradiol uptake increases of 3.2 and 1.2-fold were noted for animals receiving 8-cell embryo transfers in naturally and superovulated groups respectively. Superovulation resulted in increased progesterone uptake. Transfer of 2- and 8-cell embryos resulted in a 15.8 and 109.9% increase in progesterone uptake respectively in naturally ovulated hamsters. Similar values for superovulated hamsters were 16.2 and 87.6% respectively. The 8-cell embryos, however, were transferred about four hrs prior to the time for normal 8-cell cleavage and this, coupled with increased estradiol uptake by the embryos themselves, resulted in an elevated estradiol and progesterone uptake in the uterine tissue even when measured on Day 14 of pregnancy. The degree of increase was less with superovulated animals receiving 8-cell embryos, reflecting higher levels of estradiol and progesterone uptake in control tissues. This could account for the slight delay in development of superovulated embryos.     

Studies on the effect of 5α-androstane-3α, 17α-diol in the canine prostate in vivo

Adult beagle dogs, castrated one month previously, were treated with 5α-androstane-3α, 17α-diol (total dose 300 mg) over a period of one month. Examination of the prostate after treatment showed no significant change in size, weight or histological appearance from the castrate dog prostate. Subsequent administration of 5α-androstane-3α, 17β-diol (300 mg) over the same period of time resulted in restoration of the prostate size, weight and histological appearance to that of the normal intact dog prostate. It is concluded that exogenously administered 5α-androstane-3α, 17α-diol does not promote prostatic growth in the castrate beagle dog.     

Failure to maintain interspecific pregnancy after transfer of Dall's sheep embryos to domestic ewes

Over a 3-year period, 32 Dall's sheep (Ovis dalli dalli) embryos were transferred into 24 domestic sheep (O. aries) recipients and 4 were transferred into 2 Dall's sheep recipients. In the first year, none of the 10 O. aries recipients was diagnosed pregnant. In the following 2 years, 9 (37%) of the domestic sheep recipients were pregnant on Day 18, 8 (33%) on Day 40, 6 (25%) on Day 90 and 4 (16%) on Day 120; 1 aborted at Day 125 and another at Day 145. Pregnancies were established only in ewes that had previously been recipients of Dall's sheep embryos. The 2 remaining pregnant sheep were treated with progesterone from Day 125 until the fetuses were determined to be dead at Day 145. Both of the Dall's sheep recipients (Year 2) established pregnancies; 1 live Dall's sheep lamb was born 174 days after mating. No differences in serum progesterone, oestrone, prostaglandin F-2 alpha metabolites or cortisol concentrations could be detected during pregnancy between recipients carrying Dall's sheep embryos, recipients receiving progesterone treatment or domestic ewes carrying domestic sheep pregnancies. Six fetuses were necropsied (1 at Day 125 and 5 at Day 145-146): all fetuses were premature and had various degrees of hydranencephaly. No significant differences were found when cotyledon numbers were compared among domestic ewes carrying Dall's sheep lambs. Dall's sheep ewes lambing naturally and domestic ewes lambing naturally. These results demonstrate that the transfer of Dall's sheep embryos to domestic ewes results in the establishment but subsequent loss of pregnancy and that these losses occur throughout gestation.     

Efficacy of a prostaglandin analogue in reproduction in the anestrous mare

A prostaglandin F analogue was studied in anestrous mares: a dose-response study; a study in mares presumed pregnant; and a field evaluation of effective doses in breeding establishments. A dose of 2.0mg given by single subcutaneous injection to mares with initial plasma progesterone levels greater than 1.0ng/ml, caused luteolysis on the basis of decline in plasma progesterone concentrations. Follicle maturation leading to ovulation, accompanied by estrus, was observed, and fertility at mating either by natural service or artificial insemination was satisfactory. A dose of 1.0mg was generally effective for luteolysis, but pregnancy rates were lower than after 2.0mg. A proportion of mares which had less than 1.0mg of plasma progesterone at the time of injection ovulated and became pregnant.     

The possible mode of action of iproniazid. I. Differential luteolytic effect of iproniazid before and after the establishment of placental adolescence.

Iproniazid, a very specific monoamine oxidase inhibitor, at a dose level of 200 mg/kg body weight induced luteolysis and caused lysis of deciduomata as well as resorption of the established embryos. Exogenous replacement of prolactin, a most consistent stimulant of the endocrine functioning of corpus luteum, or progesterone absolutely reversed the adversity developed following iproniazid injection. Moreover, failure of iproniazid even at a higher dose level in the deviation of the normal sequence of pregnancy after the establishment of placental adolescence strongly tempting to suggest that iproniazid could only show its luteolytic effect when the hypothalamic-pituitary complex is exclusively involved in the maintennance of pregnancy.     

Effects of aglépristone, a progesterone receptor antagonist, administered during the early luteal phase in non-pregnant bitches

Aglépristone, a progesterone receptor antagonist, was administered to six non-pregnant bitches in the early luteal phase in order to determine its effects on the duration of the luteal phase, the interestrous interval, and plasma concentrations of progesterone and prolactin. Aglépristone was administered subcutaneously once daily on two consecutive days in a dose of 10 mg/kg body weight, beginning 12 +/- 1 days after ovulation. Blood samples were collected before, during, and after administration of aglépristone for determination of plasma progesterone and prolactin concentrations. The differences in mean plasma concentration of progesterone and of prolactin before, during, and after treatment were not significant. Also, the duration of the luteal phase in the six treated bitches (72 +/- 6 days) did not differ significantly from that in untreated control dogs (74 +/- 4 days ). However, the intervals during which plasma progesterone concentration exceeded 64 and 32 nmol/l were significantly shorter in the six treated bitches than in untreated control dogs. The interestrous interval was significantly shorter in beagle bitches treated with aglépristone (158 +/- 16 days) than in the same group prior to treatment (200 +/- 5 days ). It is concluded that administration of aglépristone during the early luteal phase in the non-pregnant bitch affects progesterone secretion, but not sufficiently to shorten the luteal phase. The shortening of the interestrous interval suggests that aglépristone administered in the early luteal phase influences the hypothalamic-pituitary-ovarian axis.