Search Results

You are looking at 11 - 20 of 24 items for

  • Author: S. R. Milligan x
Clear All Modify Search
Free access

S. R. Milligan and C. Edwards

Summary. Changes in the extracellular and blood spaces of the uterus were assessed from the distribution volumes of 51Cr-EDTA and 51Cr-labelled red blood cells during the development and regression of the artificially induced decidual cell reaction in ovariectomized, steroid-treated mice. The normally high values for uterine extra cellular space (0·35–0·40 μl/mg) fell to less than 0·20 μl/mg in association with decidual growth. Uterine blood space increased from around 0·02 μl/mg to 0·03–0·05 μl/mg with decidual development. Induction of decidual regression by removal of s.c. progesterone implants caused a rapid decline in tissue blood volume to reach control values (0·01–0·02 μl/mg) within 24 h and preceded any reduction in uterine weight. Uterine vascular permeability, as determined from the tissue accumulation of 125I-labelled human serum albumin, fell with a similar time course. Tissue extracellular space returned to the higher control values within 48 h of initiating decidual regression.

Keywords: mouse; decidual cell reaction; tissue space

Free access

S. R. Milligan and L. Martin

Summary. The hydrostatic pressures generated during controlled flushing of the mouse uterus increased at implantation and under conditions of uterine closure. These pressures may be responsible for inducing tissue damage during flushing. The possibility that samples collected by flushing might be contaminated with interstitial fluid or plasma was studied using intravenously administered51 Cr-labelled EDTA and 125I-labelled human serum albumin as markers. The presence of both tracers was detected in all flushings and was greatest in flushings from uteri with luminal closure and early implantation sites. These observations raise serious doubts about the validity of the flushing technique for analysing uterine luminal constituents in mice.

Free access

C. Edwards and S. R. Milligan

Summary. A tissue-sampling paired-tracer method was used to investigate the effect of plasma proteins on uptake by the decidualized endometrium of [3H]progesterone, [3H]oestradiol and [3H]corticosterone. When injected arterially in protein-free Ringer, the extraction of progesterone and oestradiol was 100%, while that of corticosterone was only 60%. The addition of 4% albumin or injection in mouse plasma resulted in significant decreases in progesterone extraction to about 80% and 65% respectively. Injection in pregnant guinea-pig plasma reduced progesterone extraction further (to 33%). While neither 4% albumin nor mouse plasma had any significant effect on the uptake of oestradiol, neonatal rat plasma reduced oestradiol extraction to 40%. These results are consistent with high-affinity binding proteins having a limiting effect on the availability of steroids to target tissues.

Keywords: mouse; uterus; decidua; steroid-uptake; plasma proteins

Free access

S. R. Milligan and Florence M. Mirembe

Summary. Uterine vascular permeability and tissue blood volume during the development of the oil-induced decidual cell reaction (DCR) in ovariectomized steroid-treated rats were assessed by measuring the extravascular accumulation of 125I-labelled human serum albumin and the tissue content of 51Cr-labelled red cells 30 min after intravenous administration. Within 15 min of oil instillation into one uterine horn, the vascular permeability of the horn was significantly elevated. Permeability rose to a sharp peak (10 times control levels) 9 h after oil instillation, but dropped to 5 times control values by 12 h and continued a steady decline over the next 7 days. Although a marked increase in uterine weight was associated with the development of the DCR, there was no significant change in blood volume/g tissue until 4 days after oil instillation.

Free access

P. E. Cohen and S. R. Milligan

Silastic implants containing oestradiol were developed for delivering a range of physiological concentrations of oestradiol to mice over long periods. The implants consisted of discrete lengths of Silastic tubing containing oestradiol in arachis oil, with a small reservoir of the oestradiol solution at either end of the implant. Studies showed that the release of oestradiol in vitro was proportional to the concentration of steroid within the implant. Implants containing oestradiol at concentrations from 1 to 100 μg ml−1 could induce biological responses in ovariectomized mice, ranging from minimal effects on uterine weight and vaginal smears to supraphysiological increases in uterine weight and rapid vaginal cornification. Studies of uterine vascular permeability indicated that significant effects occurred within a few hours of initial placement of the implant. These results suggest that the design of the Silastic implants described in this study provides a useful method for delivering controlled and easily manipulated physiological doses of oestradiol to mice.

Free access

S. R. Milligan and C. A. Finn

Summary. The possible role of platelet-activating factor (PAF) in the uterine responses associated with implantation was investigated. Attempts to trigger a decidual cell response in the uteri of hormonally sensitized, ovariectomized mice by instilling PAF-acether (1–1000 ng) intraluminally were unsuccessful. The effect of PAF antagonists on implantation was investigated in females ovariectomized on Day 3 of pregnancy and treated with progesterone. Implantation was induced in these females by injection of 10 ng oestradiol-17β on Day 8. Hourly intraperitoneal injections of three PAF antagonists (WEB 2086, CV 3988 and BN 52021 at doses of 1·2–1·4 mg/kg) given over a 24-h period starting 1 h before the injection of oestradiol-17β had no significant effect on the occurrence of implantation sites. Intraluminal injection of WEB 2086 (15 μg) or BN 52021 (5 μg) either 3 h before or 6 h after the nidatory oestradiol also had no significant inhibitory effect on implantation. SRI 63-441 given once daily over the first 4 days of pregnancy at a dose of 40 μg/30 g body weight had no inhibitory effect on the establishment of pregnancy. These results are not consistent with a critical role for PAF in implantation in mice.

Keywords: PAF; implantation; mouse; decidualization; PAF antagonists

Free access

S. R. Milligan and Pamela C. B. MacKinnon

Department of Agricultural Science and Department of Human Anatomy, University of Oxford, Oxford, U.K.

Ovulation in the vole (Microtus agrestis) occurs about 9-12 hr after mating (Austin, 1957; Breed & Clarke, 1970). Following ovulation, the CL may be `short-lived' and start to degenerate within 48 hr of their formation, or become fully functional when the animal becomes pregnant or pseudopregnant (Milligan, 1974, 1975a). The fate of the CL is determined by whether mating activates a reflex mechanism separate from that controlling ovulation; limited amounts of mating, e.g. a single intromission, often give rise to only short-lived CL and greater amounts of mating stimulate luteal function more consistently (Milligan, 1975a). The hormonal basis of such observations was investigated in the present study by relating the plasma levels of LH and prolactin after mating with the fate of the resulting CL.

Laboratory-bred voles (see Breed, 1969) were used ; females were mature virgins

Free access

S. R. Milligan and Florence M. Mirembe

Summary. After suitable sensitization of ovariectomized mice with progesterone and oestradiol, the intrauterine instillation of oil produces a massive decidual cell reaction. Vascular permeability, as reflected by the extra-vascular accumulation of 125I-labelled human serum albumin, increased after oil instillation and was maintained at 2–3 times control values for at least the next 3 days. Although oil instillation did not produce a decidual response in females treated with progesterone alone, an increase in vascular permeability (about 2 times control levels) still occurred. This response peaked 8 h after oil instillation and was not maintained. These results indicate that the progesterone-dominated uterus which has not been sensitized with oestradiol cannot be viewed as completely unresponsive to the stimulus of oil and demonstrate that a marked increase in vascular permeability is not itself sufficient to induce decidualization of progesterone-dominated uterine stromal cells. The uterine extravascular accumulation of 125I-labelled albumin was increased both in association with tribromoethanol anaesthesia and after oestradiol treatment of progesterone-primed animals. In pregnant mice, the appearance of Pontamine Sky Blue spots provided an earlier indication of implantation than did determination of total uterine extravascular 125I-labelled albumin accumulation.

Free access

S. R. Milligan and Fiona D. C. Lytton

Summary. Intrauterine instillation of oil, but not saline, induced both a decidual cell reaction and a marked elevation in the uterine PGF-α content of suitably sensitized ovariectomized mice. Uterine PGF-α concentrations were elevated within 5 min of the oil instillation, reached maximal levels within 30–60 min and then declined to near baseline levels again by 3 h. A similar increase in uterine PGF-α content in response to oil instillation was seen in non-sensitized females, although no decidual cell reaction developed. No significant changes in PGE or 6-oxo-PGF-1 content were observed. These results suggest that although the increase in uterine PGF-α content is not solely due to the distension of the uterus after intrauterine injection, the increase is not necessarily sufficient to induce a decidual cell reaction.

Free access

S. R. Milligan, H. M. Charlton and E. Versi

Summary. The development of luteal function in the vole is dependent on a neuroendocrine reflex which is initially activated by mating. Bromocriptine was used to destroy the CL initially induced by mating and fresh CL were induced by hormone treatment. The fate of such newly formed CL suggested that the luteotrophic effect of mating continued for about 10 days after mating, despite the destruction of the original mating-induced CL. The luteotrophic effect of mating therefore seems to be 'remembered'. A study of the fate of hormonally induced CL in females in which pregnancy had been blocked by exposure to a strange male suggested that the strange male may cause pregnancy failure by inhibiting or suppressing the luteotrophic 'mnemonic' activated by the stud mating.