The Quaternary cold periods in Europe are thought to have heavily influenced the amount and distribution of intraspecific genetic variation in both animals and plants. The phylogeographies of 10 taxa, including mammals (Ursus arctos, Sorex spp., Crocidura suaveolens, Arvicola spp.), amphibians (Triturus spp.), arthropods (Chorthippus parallelus), and plants (Abies alba, Picea abies, Fagus sylvatica, Quercus spp.), were analysed to elucidate general trends across Europe. Only a small degree of congruence was found amongst the phylogeographies of the 10 taxa, but the likely postglacial colonization routes exhibit some similarities. A Brooks parsimony analysis produced an unrooted area phylogram, showing that: (i) the northern regions were colonized generally from the Iberic and Balkanic refugia; and (ii) the Italian lineages were often isolated due to the presence of the Alpine barrier. The comparison of colonization routes highlighted four main suture-zones where lineages from the different refugia meet. Some of the intraspecific genetic distances among lineages indicated a prequaternary divergence that cannot be connected to any particular cold period, but are probably related mainly to the date of arrival of each taxon in the European continent. As a consequence, molecular genetics so far appears to be of limited use in dating Quaternary events.

Comparative phylogeography and postglacial colonization routes in Europe

Uterine leiomyomata: etiology, symptomatology, and management

1. The in vivo alkaline comet (single cell gel electrophoresis) assay (hereafter called simply the comet assay) is used for the detection of DNA strand breaks in cells or nuclei isolated from multiple tissues of animals, usually rodents, that have been exposed to potentially genotoxic material(s). The comet assay has been reviewed and recommendations have been published by various expert groups (1) (2) (3) (4) (5) (6) (7) (8) (9) (10). This Test Guideline is part of a series of Test Guidelines on genetic toxicology. A document presented as an Introduction to the Test Guidelines on genotoxicity (11) can also be referred to and provides succinct and useful guidance to users of these Test Guidelines.

Oecd guideline for testing of chemicals

While an evaluation of the estrous cycle in laboratory rodents can be a useful measure of the integrity of the hypothalamic-pituitary-ovarian reproductive axis, it can also serve as a way of insuring that animals exhibiting abnormal cycling patterns are disincluded from a study prior to exposure to a test compound. Assessment of vaginal cytology in regularly cycling animals also provides a means to establish a comparable endocrine milieu for animals at necropsy. The procedure for obtaining a vaginal smear is relatively non-invasive and is one to which animals can become readily accustomed. It requires few supplies, and with some experience the assessments can be easily performed in fresh, unstained smears, or in fixed, stained ones. When incorporated as an adjunct to other endpoint measures, a determination of a female's cycling status can contribute important information about the nature of a toxicant insult to the reproductive system. In doing so, it can help to integrate the data into a more comprehensive mechanistic portrait of the effect, and in terms of risk assessment, may provide some indication of a toxicant's impact on human reproductive physiology.

The rodent estrous cycle: characterization of vaginal cytology and its utility in toxicological studies

I.C.I. 46,474, the trans-isomer of 1-(p-\g=b\-dimethylaminoeth\x=req-\ oxyphenyl-1,2-diphenylbut-1-ene, is very effective in terminating early pregnancy by preventing implantation when given during the first 4 days after insemination to female rats. In this species, the compound is weakly and atypically oestrogenic and is also anti-oestrogenic, as indicated by its inhibitory effect on the response to exogenous oestrogens of the vaginal epithelium (cornification) and uterus (weight-increase). It is suggested that it can prevent implantation in rats by virtue of its anti-oestrogenic activity, i.e. by counteracting the oestrogen-release from the ovaries which is believed to occur on the 4th day and upon which implantation appears to depend. The corresponding cis-isomer (I.C.I. 47,699) is very different in its properties and behaves in all respects like a conventional oestrogen (orally active\p=m-\e.g.dienoestrol). In rats it is very much more potent as

/pdf/a-new-derivative-of-triphenylethylene-effect-on-implantation-znyxi33k08.pdf

A new derivative of triphenylethylene: effect on implantation and mode of action in rats

The effects of various steroids on the vaginal histology in the rat.

A Biological Classification of Progestational Agents

Potencies of oral contraceptives.

Removal of the right ovary from normal adult rats is followed by progressive hypertrophy of the left ovary that is not accompanied by measurable alteration in pituitary or serum gonadotrophins. "Total" pituitary gonadotrophin and pituitary and serum FSH and LH have been assayed during the first 12 to 16 days after hemicastration, a period of accelerated ovarian growth. Since unilateral ovariectomy does not appear to sensitize the remaining ovary to the effects of exogenous gonadotrophins, we believe that ovarian compensatory hypertrophy results from increases of gonadotrophins too subtle to be determined by the techniques employed. (Endocrinology 76: 97, 1965) R of one ovary from an animal is followed by hypertrophy of the remaining gonad, which appears to function at a level not markedly different from that of the two ovaries of the intact animal (1). The mechanism of this ovarian compensation has had little study. An attractive hypothesis would be that removal of the one ovary partially releases the hypothalamic-pituitary system from gonadal control, with subsequent increase in synthesis and release of pituitary gonadotrophins. This mechanism was assumed by Heller, Heller and Sevringhaus (2) and was the initial assumption in the use of unilaterally ovariectomized rats for the assay of the antigonadotrophic action of steroidal materials (3-5). McLaren (6) has recently cast doubt upon these interpretations by showing that, in mice at least, there is no significant increase in total pituitary gonadotrophin at five days or three weeks after operation. McLaren stated that, five days after removal of one gonad, the remaining ovary was shedding almost twice the normal numReceived June 30, 1964. ber of eggs, and that by this time there was a significant increase in gonadotrophin content of full castrates. We have carried out similar studies in rats, which will be detailed in this communication. Materials and Methods Adult female rats weighing 160-180 g were obtained from Charles River Breeding Laboratories. In each of 2 experiments a group was sacrificed on the first day of the study (day 1) and half the remaining rats were hemicastrated by removal of the right ovary. At predetermined intervals after operation, animals were selected at random from the operated and intact groups for sacrifice. In the first experiment, ovarian and whole pituitary weights were taken at autopsy; the pituitaries were fixed in acetone immediately after weighing and were air-dried. These pituitaries were subsequently ground with saline in a glass tissue grinder, and the homogenates were administered once daily for 3 days to immature female Charles River mice at a total dose of 1 pituitary/mouse; autopsy was performed on day 4. In the second study, autopsies were performed as above; however, adrenal and uterine weights and blood samples also were taken, and the neurohypophysis was dissected from the adenohypophysis. Half the 97 98 EDGREN, PARLOW, PETERSON AND JONES Volume 76

On the Mechanism of Ovarian Hypertrophy Following Hemicastration in Rats

A series of 29 compounds related to 19-nortestosterone has been studied for ability to restrict the uterine growth stimulated by 0.3 5g. of estrone. Potency (relative to progesterone) in the 19-nortestosterone series is related to the length of the side chain at 17, increasing in straight-chain forms to a peak at the ethyl (1,250% of progesterone), and then decreasing to the inactive butyl. Branching, ethyl to isopropyl (2,200%) and allyl (160%) to 1-methallyl (400%) and 2-methallyl (680%), is accompanied by a rough doubling of potency. Unsaturation affects potency: the vinyl (460%) and allyl are less potent than the ethyl and propyl (100–400%), whereas the ethynyl (800%) and propynyl derivatives (550%) are more active than their monounsaturated forms. The 5(10) dehydro isomers (estreneolones), as well as the dihydro-19-nortestosterones are much less active than the first series. 17α-Ethyl-17-hydroxy-5(10)- estren-3-one (20%) and the proply derivative (15%) are active. 17β-Hydroxy- 5(lO)-estren-3-one and ...

Richard A. Edgren

Papers

The effects of various steroids on the vaginal histology in the rat.

A Biological Classification of Progestational Agents

Potencies of oral contraceptives.

On the Mechanism of Ovarian Hypertrophy Following Hemicastration in Rats

Estrogen antagonisms: the effects of a series of relatives of 19-nortestosterone on estrone-induced uterine growth.