Hormonal Changes Accompanying Cigarette Smoke-Induced Preterm Births in a Mouse Model

Abstract

Epidemiologic evidence indicates that maternal smoking increases the risk of preterm birth. While a number of plausible mechanisms for early delivery have been offered, the role of gestational hormones in this smoke-induced outcome is uncertain. Thus, a toxicologic study was performed to examine the effects and underlying hormonal mechanisms of mainstream cigarette smoke (MCS) exposure on gestational duration. Pregnant B6C3F1 mice were exposed by inhalation to MCS for 5 days/week (4 hrs/day) from Gestational Day (GD) 4 to parturition. Smoke-induced effects on gestational length, interpubic ligament length, maternal hormone secretion patterns (estradiol-17beta, progesterone, prolactin, and relaxin), body weight gain, postimplantation loss, litter size, and offspring sex ratio were examined. Dams exposed to MCS at a concentration equivalent to smoking less than one pack of cigarettes/day (carbon monoxide = 25 parts per million, total suspended particulates = 16 mg/m3) demonstrated a significant (P < 0.05) shortening of gestational duration (compared with pregnant, air-exposed mice). In addition, MCS-exposed mice sacrificed on GD 18 had significantly (P < 0.05) increased interpubic ligament length, elevated serum estrogen levels, and a reduced progesterone to estradiol-17beta ratio (compared with air-exposed controls); levels of progesterone and prolactin were only modestly decreased and increased, respectively, in the MCS-exposed mice. Smoke exposure had no significant effects on maternal relaxin levels, body weight gain, postimplantation loss, litter size, or sex ratio. Results of this study demonstrate that inhalation exposure of pregnant mice to a low dose of MCS shortens gestation and alters hormone secretory patterns, which are important for maintaining pregnancy and inducing parturition. These findings support the view that pregnant women who smoke (even modestly) may be at increased risk for preterm birth, and that early delivery may be related (at least partly) to MCS-induced.

Measurement of sex steroids in murine blood and reproductive tissues by liquid chromatography–tandem mass spectrometry

“…This pattern of easily detectable E2 in primates but not other mammalian species does not correspond to the presence of a circulating SHBG, which is absent in rodents but not other mammals [36]. Our findings of such low (undetectable) blood E2 levels are at variance with higher values reported historically by E2 immunoassays [37][38][39][40][41][42][43][44] despite the LC-MS/MS method matching the sensitivity of these assays. This is supported by another MS-based study that showed undetectable serum E2 levels (<5 pg/mL) [45].…”

Enhanced Uterine Artery Stiffness in Aged Pregnant Relaxin Mutant Mice Is Reversed with Exogenous Relaxin Treatment1

“…This action of relaxin has been reported in several studies in male and NP female rats, in a variety of conduit and resistance arteries [26,[49][50][51][52]. Our data in pregnant mice are similar to that reported in the small renal arteries of relaxintreated, NP female Rln À/À using a dose of approximately 1 lg/h rhRLX [23].…”

“…Treatment with rhRLX for 5 days in pregnant 8-mo-old Rln À/À mice resulted in serum rhRLX concentrations of 4.85 6 0.23 ng/ml, which is equivalent to serum relaxin concentrations measured in late pregnant mice [26]. This had no significant effect on uterine artery OD, ID, WT, and wall-to-lumen ratio at rest or at 60 mmHg on Day 17.5 pregnancy (Table 1).…”

“…This dose and duration of rhRLX prevents dystocia in pregnant Rln À/À mice but does not induce premature birth [25]. This dose was predicted to yield concentrations of circulating relaxin similar to those measured on Day 18 pregnancy in mice [26]. Uterine arteries were collected on Day 17.5 pregnancy as described above.…”

Maternal allergy acts synergistically with cigarette smoke exposure during pregnancy to induce hepatic fibrosis in adult male offspring

“…CS was generated using an automated cigarette-smoking machine controlled by an adjustable peristaltic pump programmed to produce an amount of carbon monoxide (CO) and total suspended particulates (TSP) approximately equivalent to a human smoking <1 pack of cigarettes/day, that is, >25 ppm and ~15 mg TSP/m 3 , respectively (Ng et al, 2006). CO levels were monitored throughout exposure using a 48C CO Analyzer (Thermo Environmental Instruments Inc., Franklin, MA).…”