Differential effects of exogenous progesterone administration at different stages of the luteal phase on endogenous oestradiol concentration in cows.

We have investigated the effects administering exogenous progesterone, via insertion of a controlled internal drug release (CIDR) for 4 days, from either day 5 or day 12 of the oestrous cycle on plasma oestradiol concentrations. In study 1, in which progesterone was administered from day 5, measurement of plasma oestradiol in daily samples revealed a significant (p < 0.001) decrease in peripheral oestradiol concentration. In contrast, in study 2, similar administration of progesterone from day 12 had no effect on plasma oestradiol concentration. In study 3, collection of hourly samples following progesterone treatment on day 5 revealed peak progesterone concentrations within 1 h of CIDR insertion and nadir oestradiol concentrations within 4 h. The results demonstrate that treatment with progesterone early in the luteal phase causes a rapid inhibition of oestradiol secretion, while later treatment does not. While improvements in pregnancy rate following progesterone treatment at this time have traditionally been attributed to increases in progesterone, the potential involvement of decreased oestradiol secretion has often been overlooked.

Timing of follicular phase events and the postovulatory progesterone rise following synchronisation of oestrus in cows.

In cows the timing of both ovulation and the subsequent postovulatory progesterone rise are critical to successful fertilisation and early embryo development. The aim of this study was to determine the degree of variability in the timing of ovulation relative to other follicular phase events and to determine how variations in the timing of follicular phase events contribute to the timing of the postovulatory progesterone rise. Plasma concentrations of progesterone, oestradiol and luteinising hormone (LH) and the timing of oestrus and ovulation were determined following induction of luteolysis were determined in 18 mature, non-lactating Holstein-Friesian cows. Four cows were excluded on the basis of abnormal reproductive function. In the remaining 14 cows oestrus occurred at 57.4+/-4.3h and the LH surge at 54.6+/-4.0h following luteolysis (progesterone <1ngmL(-1)) followed by a fall in circulating oestradiol concentration at 64.6+/-4.4h. Cows ovulated at 88.0+/-4.7h with the postovulatory progesterone rise (to >1ngmL(-1)) occurring 159+/-7.2h after luteolysis. There was considerable variation in the timing of ovulation following luteolysis (range 64-136h) onset of oestrus (range 24-40h) and onset of the LH surge (range 24-44h). Cows were then split on the basis of interval from progesterone fall to progesterone rise giving groups (n=7 per group) with intervals of 180.6+/-6.7 and 138.3+/-5.7h (P<0.001). Between groups, both the intervals from luteolysis to ovulation (98.3+/-6.9 vs 77.7+/-3.4h; P<0.05) and ovulation to progesterone rise (82.3+/-4.2 vs. 60.6+/-5.5h; P<0.01) were longer in late rise cows. There was no difference between groups in the interval from oestrus or LH surge to ovulation. In conclusion the results of this study further highlight the high variability that exists in the timing and interrelationships of follicular phase events in the modern dairy cow, reemphasising the challenges that exist in optimising mating strategies. However, the data do suggest that in cows with poor post ovulatory progesterone secretion, the key problem appears to be poor post ovulatory development rather than a delay in ovulation.

Endometrial oxytocin receptor and uterine prostaglandin secretion in mares during the oestrous cycle and early pregnancy.

Circulating concentrations of 13,14-dihydro-15-ketoprostaglandin F2 alpha (PGFM) were measured before and after administration of oxytocin and after endometrial biopsy, with or without uterine flushing performed per vaginam, on days 10, 14 and 18 after ovulation in nine pregnant and nine cyclic mares. Concentrations of oxytocin receptor were measured in endometrial biopsy samples. Neither pregnancy status nor time after ovulation affected basal PGFM concentrations. PGFM concentrations were increased after oxytocin administration on each of the days studied in cyclic mares; on day 14 the mean response was 4.5 times higher than the mean response on days 10 and 18. In contrast, during pregnancy, responses to oxytocin administration occurred only on days 10 and 18. Marked increases in PGFM concentrations in response to endometrial biopsy occurred only on day 14 in cyclic mares and on day 18 in pregnant mares. Mean concentrations of oxytocin receptor were between 200 and 300 fmol mg-1 protein on day 10 in both pregnant and cyclic mares; in cyclic mares oxytocin receptor concentrations were increased approximately threefold on day 14 compared with days 10 and 18, but no such increase was evident during pregnancy. Total amounts of PGFM secreted after oxytocin treatment correlated with endometrial oxytocin receptor concentrations in cyclic (P < 0.001) but not in pregnant (P > 0.5) mares, and the same was true for PGFM release induced by endometrial biopsy (cyclic: P = 0.0025; pregnant: P > 0.5). The data support the hypothesis that endometrial concentrations of oxytocin receptor determine uterine prostaglandin F2 alpha secretion in cyclic mares and that endometrial oxytocin receptor concentrations are reduced in early pregnancy by a product of the conceptus. The increase in response of the pregnant uterus to oxytocin treatment or biopsy-flushing between days 14 and 18 was not due to an increase in the concentration of oxytocin receptors but presumably reflected increased receptor sensitivity.

Control of luteolysis in the one-humped camel (Camelus dromedarius).

Blood plasma concentrations of 13,14-dihydro-15-keto PGF2 alpha (PGFM) were measured in groups of mature non-pregnant and pregnant camels to study PGF2 alpha release patterns around the time of luteolysis and the timing of the signal for pregnancy recognition. Injection of each of four camels with 10 and 50 mg of PGF2 alpha showed clearly that five times the dose of exogenous hormone produced five times the amount of PGFM in peripheral plasma, thereby indicating that, as in other animal species, PGFM is the principal metabolite of PGF2 alpha in the camel. Serial sampling of three non-pregnant camels on each of days 8, 10 and 12, and three pregnant camels on day 10, after ovulation for 8 h showed a significant (P < 0.05) rise in mean plasma PGFM concentrations only on day 10 in the non-pregnant, but not the pregnant, animals. A single intravenous injection of 20, 50 or 100 iu oxytocin given to three groups of three non-pregnant camels on day 10 after ovulation did not increase their basal serum PGFM concentrations. However, daily treatment of six non-pregnant camels between days 6 and 15 (n = 3) or 20 (n = 3) after ovulation with 1-2 g of the prostaglandin synthetase inhibitor, meclofenamic acid, inhibited PGF2 alpha release and thereby resulted in continued progesterone secretion throughout the period of meclofenamic acid administration. These results showed that, as in other large domestic animal species, release of PGF2 alpha from, presumably, the endometrium controls luteolysis in the dromedary camel. Furthermore, reduction in the amount of PGF2 alpha released is associated with luteal maintenance and the embryonic signal for maternal recognition of pregnancy must be transmitted before day 10 after ovulation if luteostasis is to be achieved. However, the results also indicate that, in contrast to ruminants, the release of endometrial PGF2 alpha in the non-pregnant camel may not be controlled by the release of oxytocin.