Permanent effects of prenatal exposure to diazepam on sexual behavior of male mice.

In previous work, we found effects of prenatal exposure to diazepam (DZ) on sexual behavior of adult mice. The aim of this work was to compare sexual behavior during their reproductive span of CD-1 strain male mice exposed in utero to DZ. One group of female mice was treated with DZ (2.5 mg/kg/day; s.c.) from 6th to 17th days of gestation and a control group received saline. The spontaneous offspring male sexual activity to receptive females was tested in 3 sessions (1/week) twice, on the 6th month of age and later on the 20th. Tests were performed during the dark stage of the photoperiod and video recorded under red light. During copulating stage adult DZ-treated males showed greater incidence of interruptions of intravaginal penetration, while senile DZ-treated males had lower latencies of mount series and greater proportion of ejaculations. Both adult and senile DZ-treated males exhibited a significant larger incidence of falls and pauses during mount series with intromission. Results show a permanent effect of prenatal exposure of DZ on sexual behavior.

[Chromosomic etiology of male sterility and infertility]. / Etiología cromosómica de la esterilidad e infertilidad masculina.

Recent advances in the knowledge of sexual development have been obtained by studying individuals with dysgenetic gonads and reproductive tract alterations. By using probes Y-ADN in these patients, it was found that a gene of the short arms of Y chromosome, induces testicular differentiation. The way this gene acts is not known, but the observation that there are homologue sequencies in X and Y, suggests the possibility that sexual differentiation depends on genic doses. Other genes like the one that codifies for antigen H-Y, for skeletal maturation, body growth, dental size and spermatogenesis regulation, have been identified in chromosome Y. Findings that have allowed a better understanding of genetic and cytogenetic factor involved in sterility-infertility.

[Teratologic effects of benzodiazepines]. / Efectos teratológicos de las benzodiazepinas.

Benzodiazepines are drugs that belong to the group of minor tranquilizers. They derive from the 1-4, benzodiazepine common nucleus that was obtained by chemical synthesis and act upon the GABA receptors increasing their affinity, thus providing them with their tranquilizing, miorelaxing, and anticonvulsant properties. Due to these characteristics they have been used in a wide variety of disorders accompanied by anxiety, hyperexitability, convulsions, and muscular hypertony, as well as during pregnancy and labor. Before using them in pregnant women, the physician should consider the conditions of the product "in uterus" since, according to experimental evidences, benzodiazepines could interfere with embryonary development, mainly with those involved in central nervous system mechanisms causing tissular alterations, retardment in cellular differentiation, and behavioral disturbances. Besides, since the fetus has lower excretion rate than that of the mother, drug concentrations are greater than the therapeutic ones and fetal tolerance to the compound, administered during the last trimester, is reduced, originating abstinence or intoxication syndromes in the newborn. It is concluded that more research is needed to evaluate all the aftereffects caused by using these drugs during pregnancy.

Diazepam effect upon the microscopic structure of the mouse placenta.

CD-1 strain, female mice, aged 5 to 7 months, were mated with males of the same age. Females presenting vaginal plug were separated and randomly distributed in two groups to be treated from the 6th to 17th day of gestation. One group received single daily diazepam doses (2.7 mg/kg i.p.), the other, 0.9% saline in equivalent volumes. Females were killed on 18th day, the placentas removed and fixed in 10% formaldehyde, pH 7.3, dehydrated and embedded in paraplast; 3 microns thick sections were stained with hematoxylin-eosin and Weigert hematoxylin and analyzed under light microscopy. Placentas of the diazepam-treated females presented dilated chorion vessels and intervillous spaces. Trophoblastic cell nuclei presented chromatin in coarse granules, atypically distributed in the karyolymph, which had lesser staining affinity. Giant cells showed vacuolized cytoplasm and coarsely granulated chromatin. Results indicate that diazepam causes structural changes, possibly placental and fetal physiology.

Ca2+-agonistic effects of diazepam, a benzodiazepine 1-4 derivative, on isolated mouse and guinea pig left atria.

In normal Krebs solution, diazepam (1.75X10(-4) M) increased the action potential duration in a reversible form and caused a positive inotropic effect on mouse auricular muscle (4). 2.) Further studies on diazepam action on electrical and mechanical activity of left auricular muscle from mouse and guinea pig, in preparations electrically driven, showed that diazepam induces an increase in action potential duration measured at 20% repolarization, a decrease in the rate of spike depolarization, and modifies the conduction velocity of the action potential. 3.) Diazepam produced in preparation with spontaneous activity, positive chronotropic and inotropic effects, and positive inotropic effect in electrically driven preparations. 4.) The change in action potential duration induced by diazepam on mouse preparations was higher than on guinea pig preparations, ca.X3. 5.) These findings support that diazepam action may be due to an increase in the inward calcium current and a reduction in the inward sodium current.