Search Results

You are looking at 1 - 10 of 21 items for

  • Author: M. J. K. HARPER x
Clear All Modify Search
Free access

M. J. K. HARPER

Summary.

The amount and distribution of prenatal loss has been studied during the first pregnancy in albino rats of the random-bred, specific-pathogen-free colony maintained at Alderley Park.

Out of a total of 196 virgin female rats mated and found to have spermatozoa in the vaginal smear on the following day (Day 1 of pregnancy), fourteen (7·1%) failed to become pregnant. In 145 rats which became pregnant, the mean number of eggs shed was 12·2 ±0·19 and the mean number that implanted was 10·9 ±0·19. In eighty rats in which pregnancy was allowed to continue to the 18th to 20th day, the mean number of viable foetuses found at autopsy was 10·1 ±0·25. In various experimental groups, pre-implantation loss ranged from 9·8% to 13·9% of the eggs ovulated, the mean being 11·1% Post-implantation loss amounted to only 7·7% of the eggs ovulated, giving a total prenatal loss of 18·8%. It was found that the number of eggs ovulated was significantly related to body weight on the day of ovulation.

Out of 145 rats which became pregnant, seventy-nine (55%) showed some loss of eggs before implantation; 191 (10·8%) of the eggs were lost. Fifty-three per cent of this loss was found to be due to fertilization failure, and 43% was due to failure to develop into blastocysts. There was no correlation between the number of eggs ovulated and the number failing to develop into blastocysts, but there was a significant correlation between the number of eggs ovulated and the percentage lost before implantation. This effect, however, was confined to the individual uterine horn; the presence of large numbers of eggs in one horn did not influence the loss of eggs in the other.

In thirty-eight (55%) out of sixty-nine pregnancies some loss of embryos occurred after implantation and sixty-six (8·7%) embryos were lost. In no pregnancy in which implantation occurred were all the embryos lost. The number of eggs implanting in the uterus did not influence the percentage of embryos lost.

The mean diameter of implantation sites which survived to the end of pregnancy increased from 2·41 ±0·022 mm on Day 7 to 4·37 ±0·043 mm on Day 11 and 10·26 ±0·044 mm on Day 16. From examination of the remnants of implantation sites found in the uterus at autopsy an estimate could be made of the stages at which embryos died. Of the sixty-six lost after implantation, 73% died before Day 11, 20% between Days 11 and 13 and only 8% after Day 13. There was an indication, not reaching the level of statistical significance, that uterine crowding may have affected the amount of loss in the middle period, but it had no effect on loss in the early period.

Free access

M. J. K. HARPER

Summary.

Thirty-one virgin female rats in pro-oestrus were mated with fertile males (Day 0). Groups of four to six animals were dosed by mouth with Compound I.C.I. 33,828 (100 mg/kg) on 3 successive days starting, in different groups, on Days —1, 0, 1, 2, 3 and 4, respectively. Twelve control rats were given the vehicle only. In all groups treatment with I.C.I. 33,828 reduced the number of rats found pregnant at laparotomy, but in the treated animals found pregnant at laparotomy the mean number of implantation sites was not significantly different from that in the controls. In only one group, that dosed on Days 2 to 4, were no implantation swellings found in any animals.

The results at autopsy showed that treatment resulted in heavy mortality of foetuses after implantation in those rats in which implantation occurred. In the control rats, 6·6% of the eggs shed were lost before and 6·6% after implantation. The corresponding figures for all the treated animals were 63·7 and 30·2% respectively. Moreover, in the treated rats the development of the foetuses which survived to Day 19 was retarded, as judged by the size of the swellings on Day 8 or 11, and by the weight of the foetuses which at autopsy amounted on average to only two-thirds of that of the controls.

In an experiment in which pseudopregnant rats were dosed with I.C.I. 33,828 either before or before and after one horn of the uterus had been traumatized, it was found that the compound prevented the occurrence of a full deciduomal reaction. The effect was more marked when it was administered on Days 2 to 4 than on Days 4 to 6 of pseudopregnancy. From these results it was deduced that the compound might produce its antifertility effects by inhibiting pituitary function, thus upsetting the endocrine balance necessary for the maintenance of pregnancy.

Free access

M. J. K. HARPER

Shelesnyak was first to suggest an essential role for histamine in the process of implantation of the fertilized ovum in the rat uterus (for references see Shelesnyak, 1957). He showed (1954) that antihistaminic drugs, instilled into the uterine lumen in pseudopregnant rats, would suppress the decidual response to endometrial trauma, and demonstrated further (Shelesnyak, 1957) that pyrathiazine HCl (Pyrrolazote), which is very active in this sense, would prevent implantation in the injected uterine horns of pregnant rats if applied in the same way during the first few days post coitum. However, when given subcutaneously, Pyrrolazote® had little effect on implantation, the interference with pregnancy being greatest when the drug was administered on Days 8 to 10 after insemination (Shelesnyak & Davies, 1955). The relative inefficacy of the drug given systemically was attributed to its failure to
Free access

M. C. Snabes and M. J. K. Harper

Summary. Blastocysts recovered from oil- or indomethacin-treated donor rabbits between 5½ and 6 days after insemination and hCG injection were transferred to oil- or indomethacin-treated recipients between 135 and 147 h after hCG injection. Indomethacin treatment of donor rabbits (10 mg/kg s.c.) given every 6 h during the day before transfer had no effect on subsequent implantation of the blastocysts. However, indomethacin treatment of the recipients (10 mg/kg s.c. every 6 h from 120 to 168 h after hCG) prevented implantation of all transferred blastocysts, although 6 of the 8 rabbits died between Days 9 and 16 of (pseudo)pregnancy. Restriction of the indomethacin treatment of the recipients to only 3 injections of 10 mg/kg s.c. between 128 and 140 h after hCG injection had no effect on the implantation of the transferred blastocysts. It is concluded that indomethacin exerts its inhibitory influence on implantation via an action on the endometrium rather than on the blastocyst.

Free access

R. R. Bodkhe and M. J. K. Harper

Summary. Metabolism of PGE-2 and PGF-2α by cytosolic fractions (100 000 g supernatant) of rabbit uterus, oviduct and lung was measured in vitro. Metabolism of PGE-2 was greater than that of PGF-2α for oviduct and uterus. After an ovulating injection of hCG metabolism of both PGE-2 and PGF-2α by lung and uterus declined linearly up to 72 h (during the time of ovum transport). The amount of PG metabolism by the oviduct did not change significantly during this period, but the percentage changes of PGE-2 and PGF-2α metabolism from oestrous values did differ, and perhaps indicated a change in the ratio of intracellular PGs. No change of metabolism of either PG by lung, uterus or oviduct occurred at 24 or 72 h after an injection of 250 μg oestradiol cyclopentylpropionate given concomitantly with the hCG (a treatment regimen which causes 'tube-locking' of ova). However, progesterone treatment, in a regimen known to cause accelerated transport of ova through the oviduct, caused significantly enhanced metabolism of both PGE-2 and PGF-2α by uterus and oviduct, but not lung, 30 and 48 h later except for PGE-2 by uterus at 30 h. These results suggest that changes in metabolism of PGE-2 and PGF-2α by the oviduct may be involved in the mechanisms controlling ovum transport.

Free access

M. J. K. HARPER and A. L. WALPOLE

Summary.

I.C.I. 46,474, the trans-isomer of 1-(p-β-dimethylaminoeth-oxyphenyl-1,2-diphenylbut-1-ene, is very effective in terminating early pregnancy by preventing implantation when given during the first 4 days after insemination to female rats. In this species, the compound is weakly and atypically oestrogenic and is also anti-oestrogenic, as indicated by its inhibitory effect on the response to exogenous oestrogens of the vaginal epithelium (cornification) and uterus (weight-increase). It is suggested that it can prevent implantation in rats by virtue of its anti-oestrogenic activity, i.e. by counteracting the oestrogen-release from the ovaries which is believed to occur on the 4th day and upon which implantation appears to depend.

The corresponding cis-isomer (I.C.I. 47,699) is very different in its properties and behaves in all respects like a conventional oestrogen (orally active—e.g. dienoestrol). In rats it is very much more potent as an oestrogen than I.C.I. 46,474—by which its uterotrophic action is inhibited. On the other hand the trans-isomer is the more potent of the two in inducing vaginal cornification in ovariectomized mice.

Free access

P. Agrawal and M. J. K. Harper

Summary. Rats were treated with LH at 08:00 h on the first day of dioestrus or on Days 1 and 2 of dioestrus. Peroxidase activity increased within 3 h in females injected with LH on Day 1 and was associated with a depletion of ascorbate that lasted until the afternoon of Day 1. Values of both substances then returned to basal values by the morning of Day 2. A second LH injection on Day 2 produced effects similar to those seen after LH on Day 1. Females treated with LH did not display greater Δ5-3β-HSD activity than did controls on Day 1 after one LH injection, but did on Day 2 after two LH injections. Nonetheless, the changes were only modest by comparison with those of peroxidase. The peroxidase–ascorbate system appears to be involved in the mechanism responsible for the increased secretion of ovarian progesterone resulting from LH stimulation.

Free access

S. K. SAKSENA, R. STEELE and M. J. K. HARPER

Summary.

Groups of rats ovariectomized 5 weeks previously were injected daily for 6 days with oestradiol and/or progesterone. Although the dose of oestradiol used was adequate to suppress peripheral serum LH values, none of the treatments significantly altered the peripheral serum levels of prostaglandin F.

Free access

M. J. K. Harper, R. R. Bodkhe and W. E. Friedrichs

Summary. Metabolism of PGE-2 and PGF-2α by cytosolic fractions (100 000 g supernatant) of the uterus, oviduct and lung of rabbits treated with hCG and endotoxin (20 μg/kg) was measured. Endotoxin caused immediate decreases in metabolism of both PGs by uterus at 1 h, and these decreases became significant at 2 h for PGE-2 and 6 h for PGF-2α. The metabolism of both PGs remained depressed throughout the 24 h study. Metabolism by oviduct tissue differed in that at 1 h metabolism of both PGs increased but then remained depressed between 2 and 24 h. Metabolism of PGs by lung also showed a different pattern: that of PGE-2 was depressed only briefly (at 2 h), while that of PGF-2α was consistently depressed between 2 and 24 h. Pre-treatment with hCG did not affect the response: tissues from animals killed 6 h after endotoxin but not given hCG responded like those from animals treated with endotoxin 24 h after hCG and killed 6 h later. Much of the increased PG levels in venous drainage after endotoxin treatment can be explained by depressed ability of cells to metabolize PGs.

Free access

M. J. K. HARPER and L. E. A. ROWSON

Summary.

Sixty fertilized sheep ova were stored at 7° C in sterile sheep serum for either 72, 96 or 120 hr. Thirty of these ova were between two and six cells and after storage were transferred to the Fallopian tubes of fifteen recipient ewes. The remaining thirty ova were at the eight-cell stage or older and after storage were transferred to the uteri of fifteen recipient ewes. In each case two ova were transferred to each ewe. None of the ova survived these procedures and no lambs were born. It was observed that in the groups of ewes receiving ova which had been stored for the shorter periods, four ewes failed to return to oestrus within the normal cycle limits. It was suggested that this might indicate that some of the ova had `implanted' but failed to survive to term.

Data are also presented on the ovulatory response of Welsh mountain ewes to a standard dose of pregnant mares' serum gonadotrophin (pms) when given on the 12th or 13th day of the oestrous cycle. Some observations on the stage of development of the ova in relation to the time elapsing between the onset of oestrus and recovery are included.