Congenital malformations and transplacental cancers.

The development of the mammalian embryo can be impaired by physical and chemical exogenous agents, leading to congenital malformations or tumours. These accidents represent at present the main cause of perinatal mortality and postnatal morbidity. The principles of teratogenicity and of transplacental cancers are analysed and the therapeutical implications of the prenatal pathology are examined.

Identification and assessment of the effects of chemicals on reproduction and development (reproductive toxicology).

Most studies for determining the reproductive toxicity of a chemical have to be conducted with whole animals. Test procedures used to investigate parts or the whole of the reproductive cycle are described in current guidelines. Other techniques, such as in vitro methods, and those for investigating specific events in the cycle, are under development.

Oxetorone-induced hyperprogesteronemia and the development of uterine decidual lesions in rats.

Application of the deciduoma formation test showed that 3-benzofurol[3,2-c][1] benzoxepin-6(12H)-ylidene-N,N-dimethyl-l-propanamin-(E )-2-butenedioate (1:1) (oxetorone, L-6257, Nocertone) stimulated secretion of progesterone by the ovaries in rats and that this hyperprogesteronemia resulted from an increased secretion of prolactin. The studies carried out also showed that the apparition of uterine decidual lesions observed in certain animals undergoing chronic oxetorone treatment was linked to this hyperprogesteronemia. In view of the specific physiology of prolactin in rodents, such uterine lesions can only develop in these animals and cannot occur in man.

The teratogenic risk.

Reproduction can be impaired in animals and man by drugs and various environmental agents. Depending on the time of exposure--from fertilization through the fetal period and eventually during lactation--the consequences can range from embryotoxicity, gross malformations and a large variety of more subtle morphological, biochemical, and functional abnormalities. The high susceptibility of the embryo to exogenous agents is due to cellular multiplication and differentiation and to the lack of development of the enzyme systems necessary for the detoxification of chemicals.

[Effect of veralipride on the estral cycle, genital tract, mammary gland and pituitary gland in female rats (author's transl)].

A study of the potential biological effects of veralipride was conducted in female rats. A definite stimulating action on the mammary gland was noted, but doses of 5 to 20 mg/kg/day are required to produce secretion, which is varying from one animal to another. Follicular maturation is preserved, though there is an increase in the number of corpora lutea with more marked development in some of them.

[Pseudotumoral uterine reaction in the rat treated with a benzofuro-benzoxepin].

When orally administered, 5-(3-diméthylamino propyliden)-benzofuro [2,3-c] benzoxepin-1, which antagonizes several biogenic amines, is slightly sedative and has also endocrinological properties in the Rat, induces the appearance of localized lesions of uterine stroma in 2 to 16% of the animals. The cytological picture could suggest a tumorogenesis. In fact, these lesions represent a non-tumoral reactional hyperplasia with nuclear abnormalities due to a hormonal stimulation.

Post natal side effects in rats induced by hypolipidaemic treatment during pregnancy.

Maternal, foetal and peri- and post-natal toxicity studies of a hypolipidaemic agent, 2-[p-(2,2-dichlorocyclopropyl)phenoxy]-2-methyl propionic acid (WIN 35833), were performed on different animal species during animal evaluation of this new drug. In teratology studies in rats, mice and rabbits, no adverse effects were detected following drug exposure during the organogenesis period. In peri-natal studies, a neonatal abnormality related to treatment just before term was shown in rats.

[Action of prostaglandin F2 alpha on pregnancy in mice. Prevention of its abortive property by progesterone].

Prostaglandin F2alpha determines a high proportion of abortions in the mouse when administered before implantation at a dose level of 2 mg/kg. After implantation between days 6-8 or 7-9, doses 20 times higher are necessary to produce the effect. Daily progesterone administration, 5 mg per animal, from day 1 to day 17 allow the evolution of pregnancy in 60% of the mice even when 120 mg/kg prostaglandin is given.

[The effect of prostaglandin F2alpha on pregnancy in rats and attempts to counteract its abortifacient action].

Prostaglandin F2alpha is not teratogenic in the Rat. The frequency of abortions increases after implantation. Between day 9-14, 100% of abortions are observed.

[Endocrinotropic actions of the benzamide sultopride (author's transl)].

The influence on the pituitary hypothalamic system of Sultopride are different of those of a chemically related compound, Sulpiride. In the mammary gland the development of the acini is associated with an increase of the connective tissue. The processus of secretion, lactogenesis is quiet not stimulated.

Effects of prenatal administration of acetylsalicylic acid in rats.

Acetylsalicylic acid (ASA) administration (200 mg/kg/day) during the last six days of pregnancy in the rat has been observed to result in: (a) a prolongation of the duration of pregnancy; (b) a prolongation of the parturition time; (c) the appearance, in some individuals, of dystocia with possible secondary death of foetuses in utero.

[Trial prevention of the embryolethal properties of suramin in the mouse by adjuvant progesterone].

Suramine, a trypanocidal drug, has an embryo-lethal and teratogenic action in Rodents. Like Triton W.R.