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C. A. FINN

Summary.

Groups of old and young mice were ovariectomized and injected with hormones on a schedule to mimic the endocrine conditions of pregnancy. An artificial decidual stimulus, either trauma or the intraluminal injection of arachis oil, was applied to the left horn of the uterus and the decidual response assessed.

Following trauma, the uteri of the old mice produced significantly smaller deciduomata than those produced in the young mice. After the injection of oil there was no decidual response in the old mice, whereas in the young mice there was a good reaction in seven out of eleven animals.

It is concluded that the ability to form decidual tissue is considerably reduced in old mice, and it is suggested that this may be a significant factor in the senile reduction of litter size.

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C. A. FINN

Summary.

When unilaterally ovariectomized mice were mated, the horn containing blastocysts increased in length during the early stages of implantation, at the same time as the onset of the Pontamine Sky Blue reaction and before implantation swellings were visible macroscopically. Similarly, the horns of pseudopregnant entire mice injected with oil to induce a decidual cell reaction were longer than the uninjected horns when the response had reached the stage at which a Pontamine Sky Blue reaction could be elicited. It is concluded that growth in length of the uterus occurs during the implantation reaction and this may assist in the accommodation of blastocysts along the length of the uterus.

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C. A. FINN

Summary.

Various factors concerned in the regulation of litter size and total reproductive output in mice have been investigated. Length of daylight did not significantly affect litter size. The decline of litter size as the animals aged was associated with a high level of embryonic loss after implantation. Ligature of the Fallopian tube on one side or unilateral ovariectomy caused total reproductive output to be about halved. In the latter case, initial litter size was about three-quarters of control but decline of litter size started earlier and reproductive life-span was shorter, whereas in the former case, litter size was approximately half control level throughout but reproductive life-span was approximately equal to that of the controls. Reproductive performance of mothers that had been kept virgin or continuously pseudopregnant for the first 9 months and then paired with fertile males did not differ significantly from the performance over an equivalent period of mothers bred continuously from puberty.

The cause of the decline of reproductive capacity with age is discussed. It is suggested that it is due to the declining ability of the uterus to maintain pregnancy, associated primarily with chronological ageing.

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C. A. FINN

Summary.

The size of litters sired by male mice throughout their entire life has been followed. Each male was paired with a new young female approximately every 5 months so as to avoid any effect of ageing of the dam. There were three groups of males (1) entire, (2) unilaterally castrated and (3) 9 months younger than the first two groups. The results indicated that the individual male, regardless of treatment, had a significant influence on the size of litter sired. Unilateral castration, however, did not significantly affect litter size, nor did the age of the male.

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C. A. FINN and ANNE McLAREN

Summary.

In order to study the changes taking place in the blastocyst and locally in the uterus at the site of the blastocyst attachment, pregnant mice were killed at intervals between 3 days 21 hr and 4 days 16 hr post coitum. The uteri were tested for the presence of Pontamine Blue areas (indicating increased permeability of capillaries) and histochemically for alkaline phosphatase in the stroma, and also examined histologically. By classifying each female for the various features studied, the following order of appearance was established : Pontamine Blue reactivity, ` W-bodies' emerging from blastocyst, local oedema of the uterine stroma, alkaline phosphatase in the uterine stroma, histological decidualization. Giant cell transformation of the trophoblast occurred at about the same time as the emergence of W-bodies from the blastocyst. Blastocyst elongation began after the appearance of Pontamine Blue reactivity and before histological decidualization, but was not sequentially related to the other features studied.

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C. A. FINN and L. MARTIN

Summary.

A single injection of 15 μg actinomycin D on Day 5 after mating interrupted pregnancy in five/five mice. To obtain information about the mode of action of the drug, its effect on the progress of the artificial decidual cell reaction was studied.

Ovariectomized mice were prepared for decidualization with exogenous hormones and decidualization induced by the intrauterine injection of arachis oil. Intraperitoneal injection of actinomycin D 7½ or 1½ hr before the decidual stimulus did not prevent the early stages of the decidual reaction but delayed by 24 to 30 hr the onset of decidual transformation of the stromal cells. It appears that the drug blocks the chain of reactions leading to decidual morphogenesis after the initiation of the reaction but that once the effect of the drug wears off, development of the decidua resumes provided the hormone conditions are adequate.

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C. A. FINN and L. MARTIN

The uterus of the aged mouse does not respond to a decidual stimulus as efficiently as that of a young mouse (Finn, 1966a; Talbert & Krohn, 1966) and it is suggested that this may contribute to the decline of litter size in old mice. In young mice, closure of the uterine lumen (Potts, 1966; Finn & McLaren, 1967) and stromal cell proliferation (Finn & Martin, 1967) occur just before implantation, and are probably important in the preparation of the uterus for implantation and decidual cell formation. Both changes can be induced in ovariectomized mice; stromal proliferation by the administration of a small dose of oestrogen following several days' treatment with progesterone (Martin & Finn, 1968) ; luminal closure by progesterone alone (Martin, Finn &
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C. A. FINN and L. MARTIN

In a recent paper, it was postulated that the secretion of progesterone from the ovary during early pregnancy in the mouse does not start until the 3rd day after the finding of the copulation plug (Finn & Martin, 1969). This was based on the observation that, if pregnant mice were ovariectomized a few hours after mating and given progesterone before Day 3, the mitosis which normally occurs in the uterine glands and to a lesser extent in the luminal epithelium on Day 3 (Finn & Martin, 1967) is suppressed.

The object of the present work was to see whether exogenous progesterone given to entire pregnant mice before Day 3 would cause a similar change in the pattern of uterine mitosis on Day 3

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C. A. FINN and L. MARTIN

The control mechanisms involved in implantation can be divided into those operating from outside the uterus and intracellular controls within the organ. The hormones of the ovary ensure that uterine preparation is synchronized with the presence of a mature blastocyst in the uterine lumen, whilst the intracellular controls regulate and integrate the changes which take place within the organ and between it and the blastocyst. A prominent feature of these changes in many species is the transformation of the connective tissue stromal cells into specialized decidual cells in which the blastocyst comes to lie, either by passing through the uterine epithelium or by degeneration of the epithelium around it. This transformation will be referred to as the decidual cell reaction (DCR).

HORMONAL CONTROL

In the majority of animals implantation takes

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L. Martin and C. A. Finn

Summary. Chronically implanted IUDs consisting of silk suture threads induced decidualization in regions of the uterus remote from the suture site in ovariectomized mice treated with a regimen of progesterone and oestrogen which sensitizes the uterus to a decidual stimulus. In these conditions the IUDs did not inhibit decidualization induced by instilled oil, although they did so in pregnant animals of the same strain. Varying the dose of progesterone and oestrogen did not produce conditions in which IUDs inhibited oil-induced decidualization in ovariectomized mice and progesterone treatment did not prevent IUDs inhibiting decidualization in pregnant animals. However, when ovariectomized mice, sensitized as before, were primed repeatedly with oestrogen to simulate continuing oestrous cycles after IUD insertion, the IUDs inhibited oil-induced decidualization. This involved the premature loss of instilled oil from the uterine lumen and was associated with heavy infiltration of leucocytes into the luminal epithelium. Numbers of leucocytes free in the uterine lumen did not appear to be critical. It appears that contact between the oil and the luminal epithelial surface must be sustained for some length of time to induce a decidual reaction; brief contact is not sufficient to trigger the response.