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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

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C. Edwards and S. R. Milligan

Summary. Uterine blood flow was assessed in mice by measuring organ uptake of intravenously injected [14C]butanol. In ovariectomized mice, injection of 100 ng oestradiol-17β increased blood flow 5-fold over that of untreated controls. The injection of oestradiol-17β in progesterone-treated mice also increased uterine blood flow at the time of maximal sensitivity to a decidual stimulus, but not 4 days later. Absolute values of blood flow increased during development of the decidual cell reaction in proportion to the increase in uterine weight, reaching maximal values 96 h after decidual induction. When progesterone injections were stopped 72 h after decidual induction, a rapid decrease in absolute and relative blood flow values preceded the decrease in uterine weight. This decrease in uterine blood flow occurred within 12 h of removing a subcutaneous implant containing progesterone. These results are consistent with the view that increased uterine blood flow during decidual development may be necessary to support the rapid increase in uterine weight at implantation and the subsequent decrease in both relative and absolute uterine blood flow on withdrawal of progesterone may promote decidual regression in the mouse.

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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

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R. G. EDWARDS, L. C. FERGUSON, and R. R. A. COOMBS

Summary.

Antigens on the membrane of human spermatozoa have been investigated using the mixed agglutination and mixed antiglobulin reactions. The spermatozoal membrane was shown to possess 'speciesspecific' antigens in common with red cells which probably correspond to antigens on other tissue cells of the body.

The A and B blood group iso-antigens have been shown on the spermatozoa of secretors but not on the spermatozoa of non-secretors. The presence of the iso-antigens M, N and Tja was established; however, the sex-linked antigen Xga could not be shown on the spermatozoa.

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H. E. Edwards, K. L. Jenkins, L. C. Mucklow, G. E. Erb, and K. E. Wynne-Edwards

Factors regulating maternal serum progesterone concentrations during pregnancy in the Djungarian hamster Phodopus campbelli were investigated through changes in (1) concentrations of progesterone and oestradiol in the serum and extracted corpus luteum, non-luteal ovary, and placenta during late pregnancy, (2) prolactin concentrations in the serum, and (3) mass of the fetus, placenta, corpus luteum and non-luteal ovary. Early pregnancy (days 1–4) was characterized by surges of prolactin, corpus luteum growth and increased corpus luteum activity as indicated by increases in luteal mass, progesterone content and serum progesterone concentration. During mid-pregnancy (days 8–11) there was a loss of prolactin surges and a halt in the growth of the corpus luteum, as indicated by stable luteal mass, progesterone content and serum progesterone concentrations that were comparable with those of day 4 of pregnancy. At the same time, the non-luteal ovary began to secrete oestradiol and, on day 12, preovulatory follicles of unknown function were found. During late pregnancy (days 14–17), the prolactin surge pattern was re-established, the non-luteal ovary and corpus luteum contained oestradiol, luteal cell growth caused an increase in corpus luteum size and mass, and serum progesterone concentrations doubled. As late-term pregnancies failed to survive bilateral ovariectomy and the placenta contained little extractable progesterone, it appears that the progesterone of Djungarian hamster pregnancy is synthesized by the corpus luteum throughout gestation.

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I C McMillen, L J Edwards, J Duffield, and B S Muhlhausler

A series of epidemiological, clinical and experimental studies have shown that there are associations between the fetal and neonatal nutritional environment and the amount and distribution of adipose tissue in adult life. This review considers the evidence for these relationships and discusses the potential impact of the prenatal nutritional experience on the development of the endocrine and neuroendocrine systems that regulate energy balance, with a particular emphasis on the role of the adipocyte-derived hormone, leptin. In the rodent, leptin derived from the mother may exert an important influence on the development of the appetite regulatory neural network and on the subsequent regulation of leptin synthesis and the risk for obesity in the offspring. In species such as the human and sheep, there is also recent evidence that the synthesis and secretion of adipocyte-derived hormones, such as leptin, are regulated in fetal life. Furthermore, the hypothalamic neuropeptides that regulate energy intake and expenditure in adult life are also present within the fetal brain and may be regulated by the prevailing level of maternal and hence fetal nutrient and hormonal signals, including leptin. This work is important in determining those initiating mechanisms within the ‘fat–brain’ axis in early life that precede the development of adult obesity.

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E M Ferguson, J Slevin, M G Hunter, S A Edwards, and C J Ashworth

The present study examined the effects of feeding gilts a high fibre diet from the third post-pubertal oestrus until either day 19 of the same cycle or insemination at the following oestrus on oocyte maturity, embryo survival and associated changes in reproductive hormone concentrations. Gilts fed with the high fibre diet had lower circulating oestradiol concentrations on days 17, 18 and 19 of the cycle and increased LH pulse frequency on day 18. More oocytes recovered on day 19 from gilts receiving the high fibre diet were at metaphase II after 46-h culture in medium containing 10% of their own follicular fluid, despite fewer large (>7 mm) follicles in these gilts when compared with control animals. There was no effect of diet on ovulation rate, corpora lutea size or progesterone concentrations on days 10–12 after insemination, but embryo survival on days 27–29 after insemination was higher in gilts that received the high fibre diet. This study demonstrates that a high fibre diet that increases embryo survival also improves oocyte maturity and provides information on endocrine correlates that may shed light on underlying mechanisms.

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Ruth E. Fowler, N. L. Fox, R. G. Edwards, and P. C. Steptoe

Summary. Granulosa cells were aspirated 3–4 h before the expected time of ovulation from 10 follicles of 4 patients treated with gonadotrophins: 4 of the follicles were immediately preovulatory. The granulosa cells were cultured for 10 h with 17α-hydroxypregnenolone or dehydroepiandrosterone and samples of medium removed at 3 and 10 h were assayed for 6 steroids.

Granulosa cells were unable to synthesize androgens from endogenous substrate or undertake conversions via the Δ5 pathway, but cells from all follicles were capable of aromatizing exogenous androgens to oestrogens although this capability was reduced in cells from follicles beginning to luteinize. Granulosa cells from preovulatory follicles synthesized more progesterone from endogenous substrate than cells from follicles which had not begun to luteinize. The results provide further support for the two-cell theory of oestrogen biosynthesis whereby granulosa cells aromatize androgens which are synthesized by the thecal cells in vivo.

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D. S. FALCONER, R. G. EDWARDS, R. E. FOWLER, and R. C. ROBERTS

Summary.

The variation in the number of eggs shed by the two ovaries of mice has been examined by statistical analyses of 697 egg counts and 390 corpora lutea counts, made on mice from a variety of outbred strains, both after natural oestrus and after oestrus induced in adults by pregnant mares' serum (pms) and human chorionic gonadotrophin (HCG). The numbers of eggs or corpora lutea were distributed between sides approximately at random, the variation conforming fairly closely to a binomial distribution. This was true even after superovulation. There was, however, a slight but significant excess of variation between sides over the random amount in the egg counts, particularly after natural ovulation. Corpora lutea counts differed from egg counts in showing a slight but significant reduction of the variation below the random amount. Several possible reasons for these small deviations from a random distribution are discussed.

The correlation between the numbers of eggs shed by the two ovaries was negative after natural ovulation but positive after superovulation. This difference can be fully accounted for by the random distribution between sides together with the differences of mean and variance between natural ovulation and superovulation. The variation of total egg number was proportional to the mean egg number after natural ovulation. The variation after superovulation was much higher than after natural ovulation, even when the difference of mean was taken into account, and the greater variation of total egg number caused the correlation between sides to be positive after superovulation.