Tamoxifen inhibition of an in vitro oestradiol-induced surface coat change on mouse blastocysts.

1. Eighty-nine hour post-coitus mouse blastocysts cultured in the presence of oestradiol-17beta underwent a histochemically detectable surface coat change. 2. Tamoxifen was found to inhibit this in vitro-induced change. The role of Tamoxifen as an inhibitor of implantation is discussed.

A Canadian commercial ovum transfer unit.

Mr. Bloxham received support from the Harry Steele-Bodger Memorial Fund towards the expenses of working at the Medical School of the University of Calgary, Alberta, Canada, where he was able to continue his researches on early implantation of mammalian blastocysts. He also took the opportunity to visit the commercial ovum transfer unit near the University of Calgary and has provided the following impressions of that part of his stay in Canada.

Haemorrhagic syndrome of cattle associated with the feeding of sweet vernal (Anthoxanthum odoratum) hay containing dicoumarol.

An outbreak of a haemorrhagic diathesis in cattle fed home produced hay is described. A similar syndrome was reproduced experimentally in calves by feeding them the hay. The experimental disease was characterised by increased prothrombin and partial thromboplastin times while the leucocyte and erythrocyte counts remained normal until the terminal haemorrhage. The calves ate well and grew well until the rapid onset of progressive weakness, stiff gait, mucosal pallor, tachycardia, tachypnoea and haematomata ending in sudden death. The absence of blood coagulation was seen at necropsy while petechial, ecchymotic and free haemorrhages were found in most organs. Particularly striking were massive ecchymotic haemorrhages on the peritoneal surface of the rumen, a bloody, gelatinous mass enveloping each kidney and extensive bruising, haemorrhage and haematomata in the subcutis of the limbs. In a second feeding trial the effects of various preparations of vitamin K1 and vitamin K3 were investigated. Oral administration of large quantities of vitamin K1 reduced the elevated prothrombin time; vitamin K3 acted less consistently. Analysis of the hay for trichothecene mycotoxins was negative but floral analysis revealed that sweet vernal grass (Anthoxanthum odoratum) comprised about 80 per cent of the hay. Dicoumarol was detected in the hay and in the serum and ruminal contents of the experimental calves. The diagnosis, treatment, control and importance of this syndrome in the United Kingdom are discussed.

From ovulation to blastocyst attachment. A review of early embryonic life in the mouse.

The development of the blastocyst from ovulation to implantation is discussed with particular reference to control mechanisms that enable the embryo to attach to the uterine wall, using the mouse as a laboratory model. The physical and chemical changes in the uterus and within the blastocyst are seen as essential steps towards implantation. Evidence that the oestrogen plays a fundamental part in the overall control of these changes is demonstrated. The interrelationship between the hormones of early pregnancy and the uterine production of histamine and cycle AMP is viewed in conjunction with the development of the blastocyst and the decidual changes that occur in the uterus which are essential for nidation.

PIP: Knowledge of the hormonal, uterine, and embryonal changes that culminate in implantation in the mouse are reviewed. The major topics discussed are: 1) husbandry, 2) ovulation, 3) fertilization, 4) preimplantation: ovum development, 5) the attachment phase of implantation, 6) blastocyst collection and culture, 7) late preimplantation uterine changes, 8) delayed implantation, and 9) hormones of early pregnancy. The interrelationship between hormones of early pregnancy and the production of histamine and cyclic AMP is seen in the processes necessary for nidation. It is apparent that estrogen plays a significant role in implantation. The blastocyst is stimulated by estrogen thereby increasing its ability to attach to the endometrium and maybe helping it to escape maternal rejection. Estrogen also elicits the uterine stromal response that develops into the decidual reaction of early implantation.

An effect of Tamoxifen (I.C.I. 46,474) on the surface coat of the late preimplantation mouse blastocyst.

The oral adminitration of Tamoxifen on Days 2,3 and 4 after mating, or on Day 2 only, was found to prevent the oestrogen-dependent surface-coat change of the late preimplantation blastocyst in the mouse. It is suggested that his is an antioestrogenic manifestation and that ist is, at least in part, responsible for the drug's known antifertility effect.

Abolition of the pre-implantation surge of plasma oestrogens in mice with tamoxifen.

PIP: Tamoxifen is estrogenic in the mouse but can also prevent the estrogen-induced preimplantation surface coat change (PSCC) of the trophoblast in mice. Plasma estrogen concentrations were measured after the administration of tamoxifen on Day 2 of pregnancy. Virgin female mice were mated. Tamoxifen was given orally 40-41 hours after mating (postcoitum; pc) in a dose of 1 mg/kg of body weight. At intervals between 72-108 hours pc blood was obtained by cardiac puncture. Plasma samples of 500 microl were stored frozen until assayed for total estrogens. In an untreated group a short-lived surge of plasma estradiol occurred 84 hours pc. In this control group the mean concentration of estrogens at 82 hours pc differed significantly (p .005) from that at 84 hours. In the tamoxifen-treated group this 84-hour peak did not occur. It is concluded that tamoxifen's apparently antiestrogenic effect in preventing the trophoblasts's PSCC and implantation depends on its ability to abolish the Day 4 endogenous surge.^ieng