Development and fate of transferred rabbit ova or blastocyst in relation to the ovulation time of recipients

Atherosclerosis is a chronic inflammatory vascular disease and the predominant cause of heart attack and ischemic stroke. Despite the well-known sexual dimorphism in the incidence and complications of atherosclerosis, there are relatively limited data in the clinical and preclinical literature to rigorously address mechanisms underlying sex as a biological variable in atherosclerosis. In multiple histological and imaging studies, overall plaque burden and markers of inflammation appear to be greater in men than women and are predictive of cardiovascular events. However, while younger women are relatively protected from cardiovascular disease, by the seventh decade, the incidence of myocardial infarction in women ultimately surpasses that of men, suggesting an interaction between sex and age. Most preclinical studies in animal atherosclerosis models do not examine both sexes, and even in those that do, well-powered direct statistical comparisons for sex as an independent variable remain rare. This article reviews the available data. Overall, male animals appear to have more inflamed yet smaller plaques compared to female animals. Plaque inflammation is often used as a surrogate end point for plaque vulnerability in animals. The available data support the notion that rather than plaque size, plaque inflammation may be more relevant in assessing sex-specific mechanisms since the findings correlate with the sex difference in ischemic events and mortality and thus may be more reflective of the human condition. Overall, the number of preclinical studies directly comparing plaque inflammation between the sexes is extremely limited relative to the vast literature exploring atherosclerosis mechanisms. Failure to include both sexes and to address age in mechanistic atherosclerosis studies are missed opportunities to uncover underlying sex-specific mechanisms. Understanding the mechanisms driving sex as a biological variable in atherosclerotic disease is critical to future precision medicine strategies to mitigate what is still the leading cause of death of men and women worldwide.

Sex as a Biological Variable in Atherosclerosis.

In an attempt to study the involvement of an adrenergic mechanism in the control of ovarian function at puberty, the presence of β-adrenergic receptors wets demonstrated, and the receptors were characterized in pre- and peripubertal ovaries. Using [125I]iodohydroxybenzylpindolol (IHBP) as a ligand, a single class of high affinity, low capacity β-adrenergic sites was found in both granulosa cells and residual ovary. Analysis of Scatchard plots derived from saturation curves or kinetic analysis of association curves provided identical equilibrium dissociation constant (Kd) values for the ligand-receptor binding. Dissociation experiments showed that the ligand binding to the receptor had the presence of both loosely bound, easily displaceable and tight, nondisplaceable components. IHBP binding was inhibited by L-propranolol [inhibition constant (Ki) = 10.5 nM], isoproterenol (Ki = 696 nM), and zinterol, a β2-adrenergic agonist (Ki = 187 nM). Metoprolol, a β1-antagonist, exhibited a much higher Ki (5.3 μM). C...

Ovarian β-adrenergic receptors during the onset of puberty: Characterization, distribution, and coupling to steroidogenic responses

New Zealand virgin rabbits were used in this study. Normal males and castrated, thyroidectomized and recently mated females formed the control groups. Correlation with the light microscopical appearance using the method of alternate thin and thick sections, correlation with the control glands, and comparison with the descriptions in the rat, were used as criteria for the identification of five different types of secretory cells in the pars distalis. Two types of “acidophiles” were found, the more numerous and conspicuous having secretory granules of a maximum diameter of 380–400 mm (growth hormone-producing cell), and a second type with granules of 600–800 mm, very seldom seen in the virgin rabbit but increasing in number and granulation after mating (Prolactin-producing cell). Two types of “basophiles” that correspond to the “thyrotrophes” (angular shape, granules of 150 mm in diameter) and “gonadotrophes” (rounded shape, granules of 280–300 mμ), were also identified. In addition, a peculiar large cell with characteristic mottled cytoplasm and very few granules was tentatively identified as a “basophile” in the process of regranulation. Its functional significance was discussed. A stellate cell having fibrillar material and no secretory granules within its cytoplasmic processes, found between parenchymal cells and approaching basement membranes, was tentatively identified as a supporting element. In addition to the description of the fine structure and possible functional significance of the different cell types, some features as cilia, desmosomes, intranuclear fibrillar material, as well as vacuolization of cells in normal glands were also discussed.

The pars distalis of the female rabbit hypophysis: an electron microscopic study.

Of the many suggested tests for pregnancy none is entirely satisfactory. A new pregnancy test, apparently highly accurate, is presented. It is inexpensive and simple to perform in the office without the use of animals or the aid of an outside laboratory. In suitably selected patients, and nearly all can qualify, three injections of estrone in oil, 1 mg. each, are given over a period of five days. If the patient fails to have vaginal bleeding within twenty-four hours after the third dose of estrone, she may be presumed to be pregnant. The test has been 100 per cent accurate in over 250 cases. Fifty cases are presented, with controls.

New pregnancy test; use of three injections of estrone in oil.

Mechanism of ovulation in the rabbit

STUDIES ON THE UTERUS: III. The Activity of the Uterine Fistula in Unanesthetized Rabbits Following Coitus and During Pseudopregnancy

THE MECHANISM OF OVULATION IN THE RABBIT: I. The Demonstration of a Humoral Mechanism

STUDIES ON THE UTERUS: IV. The Response of the Uterine Fistula of the Unanesthetised Rabbit to the Injection of Urine from Pregnant Women

1. The post-partum rabbit responds with great regularity to the injection of one minimal effective dose of an extract of urine of pregnancy.\n\n2. Because of this regularity, and the rapidity and ease with which the results may be determined, it is recommended that the post-partum rabbit be given a trial in the bioassay of gonad-stimulating extracts.\n\n3. Follicles discharged by one m.e.d. of an extract of urine of pregnancy undergo a process of luteinisation similar in rate and magnitude to that seen in pseudopregnancy. The lutein tissue produced in such artificially discharged follicles sensitizes the uterus for the production of decidual tumours.\n\n4. In face of the data obtained from the experiments with repeated subminimal doses, it is impossible to explain the luteinisation of artificially discharged follicles solely on the basis of the storage and subsequent utilisation of some of the injected material.\n\n5. It is possible to luteinise unruptured follicles in the rabbit ovary by the administration of an extract of urine of pregnancy at rate below that which is required to provoke ovulation.

Maurice Harold Friedman

Papers

Mechanism of ovulation in the rabbit

STUDIES ON THE UTERUS: III. The Activity of the Uterine Fistula in Unanesthetized Rabbits Following Coitus and During Pseudopregnancy

THE MECHANISM OF OVULATION IN THE RABBIT: I. The Demonstration of a Humoral Mechanism

STUDIES ON THE UTERUS: IV. The Response of the Uterine Fistula of the Unanesthetised Rabbit to the Injection of Urine from Pregnant Women

On the mechanism of ovulation in the rabbit