Maternal aerobic exercise: newborn effects.

Maternal aerobic exercise during pregnancy may affect the experience of labor for the mother or fetus. Forty-four women who had given birth in the preceding 7 months responded to questions about their exercise habits during pregnancy. Using an exercise prescription formula, respondents were dichotomized into exercise or nonexercise groups. Maternal exercise was associated with a significant decrease in the duration of the second stage of labor (27 minutes vs 59 minutes, p = 0.04) and a reduction in the incidence of obstetric complications (8 vs 19, p = 0.058). The groups showed no significant differences in the number of weeks gestation, duration of the first or third stage of labor, birth weight, birth length, or neonatal Apgar scores at one and five minutes.

Embryotoxicity in mice of phosphonacetyl-L-aspartic acid (PALA), a new antitumor agent. I. Embryolethal, teratogenic, and cytogenetic effects.

The embryolethal and teratogenic effects of phosphonacetyl-L-aspartic acid (PALA), a new antitumor agent, were evaluated in pregnant Swiss albino mice that received multiple IP injections of drug on days 7-11 of gestation. The effects of single doses of PALA given IP on days 4, 5, 6, 7, 8, 9, or 10 of gestation were also examined. Cytogenetic studies were performed on cells from embryos exposed in utero to embryotoxic doses of PALA, as well as on human peripheral leucocytes incubated with PALA for six or 48 hours. When given on days 7-11 of gestation, marked embryolethal effects were noted at PALA doses of 1.5 mg/kg/day, and no embryos survived doses of 6.25 mg/kg/day. Studies on the effects of PALA administered as a single dose on various days of gestation revealed that its embryolethal effects were gestation stage-specific; 80% of embryos were killed in utero after exposure to a dose of 12.5 mg/kg on day 8, whereas doses nearly 20-fold higher (200 mg/kg) were required to exert equivalent embryolethal effects on day 6 or 10 of gestation. PALA treatment induced an increase primarily in the incidence of malformations which occur spontaneously in control mice rather than in malformations not normally seen in controls. PALA embryotoxicity in mice apparently does not derive from major cytogenetic damage, as the incidence of chromosomal aberrations was not significantly increased by in vitro or in vivo exposure to PALA.

Embryotoxicity in mice of phosphonacetyl-L-aspartic acid (PALA), a new antitumor agent. II. Studies on its mechanism and reversibility.

The embryolethal effects of phosphonacetyl-L-aspartic acid (PALA) are markedly gestational stage-specific in the Swiss albino mouse. Embryos are most sensitive to the lethal effects of PALA on days 7 and 8 of gestation, with embryonic LD50's of 9 and 8 mg/kg, respectively. In contrast, the embryonic LD50 on day 10 of gestation is 144 mg/kg. Following an IP dose of (acetyl-14C)-PALA to pregnant mice, approximately threefold higher levels of radioactivity were present in day 8 than in day 10 embryonic tissue, whereas the radioactive content of placentas from day 10 pregnant animals was significantly higher than in placentas from day 8 pregnant mice. Similarly, L-aspartate transcarbamylase (ATCase) activity was greater in maternal spleen, placentas, and embryos on day 8 than on day 10 of gestation, and PALA treatment produced a greater inhibition of ATCase in embryonic tissue on day 8 than on day 10; however, inhibition of placental ATCase activity was more pronounced on day 10 than on day 8. Neither single nor multiple doses of uridine (UR) given orally to pregnant mice on day 8 of gestation were effective in reducing day 8 PALA embryolethality. Carbamyl-L-aspartic acid, given in the drinking water of pregnant mice on days 7-9 of gestation, reduced the day 8 embryolethality of PALA from 100% to approximately 50%. In a similar experiment, the presence of UR in the drinking water of pregnant mice reduced PALA-induced embryolethality in day 10, but not day 8, embryos. These results indicate that the embryotoxic effects of PALA are the result of ATCase inhibition; furthermore, they suggest that the relative insensitivity of the day 10 embryo to the lethal effects of PALA may result either from a greater availability of UR to the day 10 (versus the day 8) embryo, or from an enhanced ability of the day 10 placenta to bind PALA and prevent its passage into the embryo.

Teratogenic and cytogenetic effects of some plant-derived antitumor agents (vincristine, colchicine, maytansine, VP-16-213 and VM-26) in mice.

The teratogenic effects of three new plant-derived antitumor agents, maytansine, VP-16-213 and VM-26, were compared to the effects of vincristine and colchicine in pregnant Swiss albino mice that received a single ip injection of drug on day 6, 7 or 8 of gestation. Cytogenetic studies were also performed using maternal bone marrow and embryos obtained 48 hours after injection of maytansine, vincristine, VP-16-213, VM-26 and colchicine on day 6, 7 or 8 of gestation. A close correlation between teratogenic and cytogenetic effects was not noted among the compounds tested. Vincristine had greater embryotoxic and teratogenic activity than maytansine at equimolar doses (0.36 mu moles/kg), with the peak effects appearing after injection on day 7 of gestation. Colchicine, VP-16-213 and VM-26 were comparatively less potent than maytansine and vincristine, since doses of 2.5 mu moles/kg (colchicine and VP-16-213) and 1.5 mu moles/kg (VM-26) were required to elicit embryotoxic effects. At their teratogenic doses, all compounds induced various cranial abnormalities including exencephaly, hydrocephalus, anophthalmia and microtia, as well as major skeletal malformations. The teratogenic dose of vincristine is comparable to its effective antitumor dose in transplantable rodent tumor systems; in contrast, the teratogenic dose of maytansine in approximately 10-fold higher than its antitumor dose. Of the compounds studied, VP-16-213 and VM-26 exerted the most consistent cytogenetic effects in embryonic tissue. Alarge proportion of the structural chromosome aberrations induced in embryonic cells by VM-26 were stable and are most likely capable of surviving at least one cell division.