The effect of aprotinin on luteolytic and uterine contractile mechanisms in the pregnant rat at term.

The effect of the kallikrein inhibitor aprotinin on luteal function, uterine activity and parturition was studied in primigravid pregnant rats. Luteal function was monitored by the determination of serum progesterone levels. Aprotinin given daily from Day 19 to Day 22 of gestation had no effect on progesterone concentrations compared to saline-treated controls, but indomethacin delayed the decline in progesterone levels over the same time period. Aprotinin treatment had no effect on fetal and placental weights from Days 19 to 22 of gestation. Aprotinin infusion in Day-22 pregnant rats resulted in a reduction in uterine motility (studied by continuous recording in conscious rats by means of an intrauterine microballoon) in 10/12 rats. Continuous infusion of aprotinin into rats which had been allowed to deliver one young resulted in a significantly prolonged duration of parturition compared to that in saline-infused controls. In one rat the delivery process was completely arrested and recommended only when the infusion was stopped. Aprotonin had no effect on either the spontaneous or oxytocin-induced uterine contractions of the isolated Day-22 pregnant rat uterus. It is concluded that the kallikrein-kinin system in the late pregnant rat does not appear to be involved in the luteolytic process but may play a functional role in the control of uterine and/or cervical function before and during parturition.     

Myometrial adenylyl cyclase protein decreases on the last day of pregnancy in the rat

To determine whether gestation-related changes in responsiveness of the rat uterus to beta-adrenergic agonists are mediated at the level of adenylyl cyclase, we measured myometrial adenylyl cyclase activity and protein quantities during pregnancy and labor. In rat myometrial membranes, basal adenylyl cyclase activity increased from the nonpregnant state to mid (Days 12-14) and then late (Days 18-20) gestation and then decreased intrapartum (Day 22). Stimulated adenylyl cyclase activity, at the level of the beta-adrenergic receptor (isoproterenol, 10(-4) M), the G protein (GTP, 10(-5) M), or the adenylyl cyclase enzyme (MnCl(2), 20 mM), was similarly altered during gestation. Total adenylyl cyclase protein was quantified by [(3)H]forskolin binding assay in myometrial membranes from nonpregnant and pregnant (Day 14, Day 20, Day 21, and intrapartum Day 22) rats. Adenylyl cyclase protein increased progressively from nonpregnant rats to pregnant rats at mid (Day 14) and late (Day 20) gestation, but it decreased abruptly to nonpregnant levels on Day 21, the day before parturition, and remained at similar levels on Day 22 (intrapartum). The gestation-related increase in expression of myometrial adenylyl cyclase protein may facilitate uterine quiescence during pregnancy, and the abrupt decrease of adenylyl cyclase protein on the last day of pregnancy may be a contributing mechanism for the initiation of labor.     

Sex difference in whole-body androgen content in rats on fetal days 18 and 19 without evidence that androgen passes from males to females

The whole-body content of androgen (testosterone + 5 alpha-dihydrotestosterone) was significantly higher on Fetal Days 18 and 19 in male than in female rats; androgen content was equivalent in the two sexes at other fetal ages, including Days 16, 17, 20, and 21, and prior to parturition on Fetal Day 22. These results partially corroborate previous data of Weisz and Ward (Endocrinology 1980; 106:306-316), who measured testosterone in pooled plasma from rat fetuses and suggest that androgens contribute to masculine brain sexual differentiation only briefly during fetal life. No significant differences in whole-body androgen content were observed among groups of females situated in utero between 0, 1, or 2 males on each side (contiguous male model) or among groups of females with 0, 1, or 2 or more males located caudally (on the cervical side) in the same uterine horn, regardless of whether combined data from Fetal Days 17-22 or only Fetal Days 18 and 19 were considered. These results provide no evidence that androgens from males reach female fetuses in the same uterine horn.     

Trypanosoma lewisi and T. cruzi: Effect of infection on gestation in the rat

Termination of pregnancy occurred in the rat after infection with Trypanosoma lewisi early in gestation. Rats were inoculated on Day 2 of pregnancy and the uteri were excised and examined on Days 10 and 14 of gestation. There were no detectable differences in size in the fetuses of infected and control females at Day 10, but by Day 14 young of infected females were being reabsorbed, and their weight was markedly less than that of control young.A bioassay of estrogens and progestogens based on the decidual cell response indicated that there was a sufficient hormone level to maintain pregnancy beyond Day 10, so the mechanism of action by which fetal death was produced did not appear to be hormone depletion. The crucial changes in fetal weight occurred between Days 12 and 14 of gestation in rats infected with T. lewisi on Day 2 of gestation.Trypanosoma cruzi caused little or no pathologic change in the pregnant laboratory rat throghout the period of gestation and infected females gave birth to apparently normal young.     

Peripheral plasma levels of oestradiol-17 beta and progesterone in the bitch during the oestrous cycle, in normal pregnancy and after dexamethasone treatment.

Plasma oestradiol-17 beta concentrations in Labradors increased during pro-oestrus to an average maximal concentration of of 79-7 +/- 10-9 (S.D.) pg/ml, and then fell rapidly. In 6/7 bitches the peak occurred within 1 day of oestrus. No consistent changes in plasma oestradiol levels were observed during pregnancy and at parturition and the values were similar to those in late anoestrus. Plasma progesterone levels did not increase markedly during pro-oestrus. At oestrus, progesterone values rose and maximal concentrations, which varied from about 20 to about 55 ng/ml, were reached within a few days of the oestradiol peak. Plasma progesterone decreased in late pregnancy and in one of the three bitches studied in detail low or undetectable levels were reached 10 days before parturition. In the other two bitches an abrupt decrease in progesterone occurred just before parturition. Dexamethasone treatment (2 X 5 mg daily for 10 days) from Day 30 of pregnancy resulted in intrauterine death and resorption of the fetuses in the two bitches studied. Treatment from about Day 45 resulted in the birth of dead fetuses at Days 55 and 59 of pregnancy. The changes in plasma oestradiol levels were very small. No changes in plasma progesterone levels were seen when dexamethasone was given in late pregnancy, but an accelerated decline occurred after treatment in mid-pregnancy.     

Ontogeny of the response to growth hormone-releasing factor

Primary cell cultures were prepared from fetal, neonatal and adult rat pituitaries and evaluated for their ability to secrete growth hormone (GH) in response to growth hormone-releasing factor (GRF). Pituitary cells prepared from fetuses at days 19 and 21 of gestation, neonatal animals at the day of birth (day 0) or the following day (day 1) and peripubertal male rats showed full dose response curves to GRF with maximal GH release when stimulated with 1 X 10(-10) M rat GRF. At this concentration of GRF, the amount of GH released was not different from that elicited by activation of adenylate cyclase with 1 X 10(-5) M forskolin. In contradistinction, a preparation of cells from fetuses at day 18 of gestation did not show the same release of GH when challenged with 1 X 10(-10) M GRF and forskolin (0.057 +/- 0.001, compared to 0.076 +/- 0.003 micrograms/10(5) cells per 4.5 h), although the cells clearly responded to both secretagogues (basal levels of GH, 0.029 +/- 0.002 micrograms/10(5) cells per 4.5 h). While cells prepared from fetuses at day 21 of gestation or from animals after birth released 5-10% of their total cellular GH content, those prepared from 18- and 19-day fetuses released as much as 40% of their total GH suggesting there is a maturation of intracellular GH processing that occurs late in gestation. The results show that, in late pregnancy, the rat fetal pituitary is highly responsive to growth hormone-releasing factor and suggest that this peptide participates in regulating GH levels during the perinatal period.     

Effects of progesterone on parturition in the tammar, Macropus eugenii

Tammar wallabies were treated with progesterone injections or implants during late pregnancy to determine whether progesterone withdrawal was essential for parturition. Neither physiological (implanted group) nor pharmacological (injected group) levels of circulating progesterone prevented parturition occurring at about the expected time in about two-thirds of animals that were pregnant. The neonates of both groups were normal in size and weight, but about a third of treated pregnant animals retained their fetuses or aborted. The retained fetuses were retarded in development. Therefore, progesterone treatment had no influence on the duration of gestation, or parturition, in the tammar wallaby, but high progesterone concentrations may interfere with the normal course of development and birth in a proportion of treated animals.     

Hypothalamic influence on differentiation of the immunoreactive ACTH beta-LPH, alpha- and beta-endorphin containing cells in adenohypophysial primordia of rat fetus in organ culture (author's transl)]

Adenohypophysial primordia were isolated in rat fetuses from day 12.5 to day 15.5 of gestation. The organ culture employed for maintenance of the primordia was made up according to Watanabe et al. (1973). The fixation of primordia in Bouin Hollande's solution was performed after 9, 8, 7 or 6 days of culture when the normal duration of pregnancy was achieved. The cultivated primordia were immunologically studied using different antisera: anti-alpha(17-39)ACTH, anti-beta(1-24)ACTH, anti-beta-LPH, anti-alpha and anti-beta-endorphins, with immunoperoxidase or immunofluorescence techniques, including control experiments of the specificity of the antisera. A similar study was performed on pituitaries removed from normal rat fetuses from day 16.5 of gestation and each day up to birth, and fixated immediately. In vivo the first cells reacting with all the antisera used in this study were observed on day 16.5 of gestation; their number increased during gestation (Fig. 1 A, B and C). Immunoreactive cells with the different antisera could be detected in primordia isolated on day 12.5 of gestation after 9 days of culture. Numerous groups of cells were observed in primordia of older fetuses (Fig. 2 A and B). These data indicate that the corticotropic cells in rat fetuses could start to be differentiated without stimuli from the hypothalamus since primordia were isolated before the appearance of this cell type in normal rat fetuses and before the differentiation of the hypothalamus. The presence of ACTH and other peptides such as beta-LPH or beta-endorphin would support the hypothesis of a common precursor in this cell type existing early in gestation. Similar results were obtained in human fetuses.     

Spacing of conceptuses in the uterine horn and local effects on fetal and placental weights throughout gestation in the rat

Longitudinal growth of the uterine horn and distances between implantation sites and the extremities of the horn were measured in 30 albino Wistar rats at Days 7, 10, 13, 16 or 22 of gestation. Growth of the uterus was most rapid over Days 13-16 but continued over Days 16-22. Distances between implantation sites and between the extremities of the uterine horn and neighbouring implantation sites were relatively even in that the coefficients of variation of these distances were 28, 32, 19, 35 and 35% at Days 7, 10, 13, 16 and 22, respectively. This indicates that an active mechanism promotes even spacing since the expected coefficients of variation given completely random spacing of conceptuses was calculated to be about 100%. Local crowding of fetuses in the uterine horn did not appear to affect fetal or placental growth except at Day 22 when there was a weak but significant correlation (r = 0.3) between fetal weight and the harmonic mean distance to neighbouring implantations.     

Insulin-like growth factors and their binding proteins define specific phases of myometrial differentiation during pregnancy in the rat

While the insulin-like growth factor (IGF) system is known to regulate uterine function during the estrous cycle, there are limited data on its role in myometrial growth and development during pregnancy. To address this issue, we defined the expression of the Igf hormones (1 and 2), their binding proteins (Igfbp 1-6), and Igf1r receptor genes in pregnant, laboring, and postpartum rat myometrium by real-time PCR. IGF family genes were differentially expressed throughout gestation. Igf1 and Igfbp1 mRNA levels were upregulated during proliferative phase (Days 6-12) of rat gestation. Igfbp3 gene expression also was elevated in proliferating smooth muscle cells (SMCs) and was highest at the time of transition between proliferative and synthetic phases (Days 12-15). Igfbp6 gene expression profile paralleled plasma progesterone (P4) concentrations, peaking during the synthetic phase (Days 17-19) and decreasing thereafter. Administration of P4 at late pregnancy (starting from Day 20) to maintain elevated plasma P4 concentrations blocked the onset of labor and prevented the fall in Igfbp6 mRNA levels. In contrast, the treatment of pregnant rats with the P4 receptor antagonist RU486 on Day 19 induced preterm labor and the premature decrease of Igfbp6 gene expression. Igfbp2 gene expression was transiently upregulated during the contractile phase of gestation (Days 21-23) solely in the gravid horn of unilaterally pregnant rats, but it was not affected in P4- or RU486-treated animals, supporting a role for mechanical stretch imposed by the growing fetuses. Igfbp5 gene was induced during postpartum involution. Our results suggest the importance of the IGF system in phenotypic and functional changes of myometrial SMCs throughout gestation in preparation for labor.     

Evidence for a noradrenergic transmission in the control of parturition in the rat

6-Hydroxydopamine, when injected at 14:00 h on Days 21 and 22 of pregnancy in the rat (2 X 50 mg/kg), markedly decreased plasma and uterine noradrenaline concentrations (-60% and -82% respectively; P less than 0.001). As a consequence of this treatment, there was severe disturbance in the distribution pattern of parturitions: 61% of rats had suppressed parturition and 31% of rats displayed a lengthened or interrupted labour. A bolus dose of prazosin (3 mg/kg) administered at 12:00 h on Day 22 completely blocked the normal process of parturition throughout the next 6 h, a result which is compatible with the half-life of the drug (2.9 +/- 0.8 h). Administration of phentolamine (3 mg/kg) at term induced a significant decrease of uterine activity (frequency X duration of bursts of spike potentials) as revealed by electromyographic recordings in vivo. These results suggest that noradrenaline released from sympathetic nerve terminals interacts with alpha-adrenoceptors located post-synaptically to improve the overall excitability of the myometrium at the onset of labour.     

Evidence for placental abnormality as the major cause of mortality in first-trimester somatic cell cloned bovine fetuses

The production of cloned animals is, at present, an inefficient process. This study focused on the fetal losses that occur between Days 30-90 of gestation. Fetal and placental characteristics were studied from Days 30-90 of gestation using transrectal ultrasonography, maternal pregnancy specific protein b (PSPb) levels, and postslaughter collection of fetal tissue. Pregnancy rates at Day 30 were similar for recipient cows carrying nuclear transfer (NT) and control embryos (45% [54/120] vs. 58% [11/19]), although multiple NT embryos were often transferred into recipients. From Days 30-90, 82% of NT fetuses died, whereas all control pregnancies remained viable. Crown-rump (CR) length was less in those fetuses that were destined to die before Day 90, but no significant difference was found between the CR lengths of NT and control fetuses that survived to Day 90. Maternal PSPb levels at Days 30 and 50 of gestation were not predictive of fetal survival to Day 90. The placentas of six cloned and four control (in vivo or in vitro fertilized) bovine pregnancies were compared between Days 35 and 60 of gestation. Two cloned placentas showed rudimentary development, as indicated by flat, cuboidal trophoblastic epithelium and reduced vascularization, whereas two others possessed a reduced number of barely discernable cotyledonary areas. The remaining two cloned placentas were similar to the controls, although one contained hemorrhagic cotyledons. Poor viability of cloned fetuses during Days 35-60 was associated with either rudimentary or marginal chorioallantoic development. Our findings suggest that future research should focus on factors that promote placental and vascular growth and on fetomaternal interactions that promote placental attachment and villous formation.     

Insulin receptors in developing rat liver: Acquisition of down regulation in the immediate postnatal period

Alterations in the high and low affinity insulin receptor concentrations in developing rat liver were investigated. The number of high affinity receptors in partially purified plasma membranes from fetal rats increased from Days 19 through 22 of gestation, with no further increase in binding during the postnatal period. Fetuses of diabetic rats had approximately three times as many high affinity insulin receptors as age-matched fetuses of normal rats; however, by 1 day after birth the receptor number decreased to the normal level. Neither the number of low affinity receptors nor the affinity of insulin binding to high or low affinity receptors changed during development or between offspring of normal and diabetic rats. These changes in the number of high affinity hepatic insulin receptors from prenatal animals did not correlate with the concentration of plasma insulin. When suckling pups were rendered diabetic the changes in the number of high affinity insulin receptors correlated with alterations in plasma insulin concentrations. The number of high affinity sites/microgram DNA in hepatocytes from Day 18 fetal rats was not altered when cells were cultured for 48 h in medium containing 0, 250, or 5000 μU/ml of added insulin. When cultured hepatocytes derived from 1-day-old and adult rats were maintained in medium with added insulin concentrations of 250 or 5000 μU/ml the number of high affinity receptors/microgram DNA decreased as compared to the number of high affinity receptors in hepatocytes cultured in medium with no added insulin. This decrease in receptor number was accompanied by an increase in the affinity of insulin binding to its high affinity receptors. The data show that (i) only the high affinity insulin receptor number increases in rat liver during the prenatal period, (ii) fetuses of diabetic rats show a greater increase in high affinity receptors than do fetuses of normal animals, and (iii) the phenomenon of down regulation for high affinity insulin receptors is not observed in fetal rat liver, but is acquired in the immediate postnatal period.     

Ultrasonographic analysis of gestation in mink (Mustela vison)

Mink are seasonal breeders that display an obligate delay preceding implantation and a post implantation gestation of 31 d. The purpose of this study was to evaluate gestational parameters in mink by ultrasonography. A total of 92 female mink were mated twice during the period from March 2 to 20. The mink were scanned once and allowed to whelp (n=55); or scanned at 3 to 5-d intervals until parturition (n=13); or immediately subjected to autopsy (n=24) after scanning. Embryonic age was calculated from the date of parturition or from crown rump length. Uterine swelling diameter and fetal head size were correlated with embryonic age. The gestational sac grew rapidly once implantation had occurred. Uterine swellings of 4 to 5 mm in diameter were found on Days 2 to 4 post implantation and increased through Days 18 to 20, at which time they began to elongate due to the longitudinal growth of the fetus. Fetal cardiac activity could be detected on Days 10 to 12 post implantation in live embryos. The heart frequency was 198 +/- 3.0 beats per minute and did not vary from Days 12 to 30 post implantation. Fetal head diameter of 5 mm was first detected on Day 19 post implantation and grew gradually to 9 to 10 mm at parturition. It was not possible to accurately assess the number of conceptuses in utero. We conclude that ultrasonography can be employed in mink to diagnose pregnancy, to predict the parturition date and to determine the presence of live fetuses.     

Parturition and recruitment of macrophages in cervix of mice lacking the prostaglandin F receptor

Parturition does not occur in transgenic mice lacking the prostaglandin F receptor (Ptgfr(-/-)) because luteolysis is forestalled and progesterone production persists. Ovariectomy of pregnant Ptgfr(-/-) mice leads to a decline in circulating progesterone and delivery of live pups. The objective of the present study was to test the hypothesis that immigration of macrophages and increased innervation of the cervix of Ptgfr(-/-) mice was associated with ripening and parturition. The cervix of pregnant Ptgfr(-/-) mice was studied on Days 15-21 after breeding; additional groups were ovariectomized on Day 19 of pregnancy, and the cervix obtained on Day 20 of pregnancy before birth or the next day at about 24 h after birth. On Days 18-19 of pregnancy, macrophage numbers and nerve fiber density increased more than 3-fold compared with findings in nonpregnant or Day 15 or 21 pregnant Ptgfr(-/-) mice. The magnitude and time course of these changes were comparable to those found in wild-type controls that delivered on Day 19 after breeding. Thus, the mechanism regulating macrophage immigration, innervation, and cervical remodeling in Ptgfr(-/-) mice with delayed parturition is similar to wild-type controls that deliver at term. By contrast, ovariectomy forestalled the decrease in cervical macrophages in Ptgfr(-/-) mice. By Day 21 after breeding, macrophage numbers more than double those after ovariectomy, relative to those found in pregnant Ptgfr(-/-) mice, whereas nerve fiber density was the same regardless of birth. Density of collagen structure in these mice directly matched macrophage traffic in the cervix. The findings indicate that the prostaglandin F(2alpha) receptor and progesterone withdrawal are a necessary part of the final common pathway for ripening of the cervix and the process of parturition.     

Effect of maternal alcohol consumption on the fetal thyroid in the rat

To investigate the effect of maternal alcohol consumption on the development of the fetal thyroid gland, Sprague-Dawley rats were given 20% ethanol for 4 weeks prior to mating and 30% ethanol throughout gestation. Pair-fed controls received an isocaloric amount of corn starch and chow, with water ad libitum, and ad libitum controls received rat chow and water. On Days 17, 18, 19, and 20 of gestation, the fetuses were weighed and the fetal thyroids were removed for histometric observation. On Days 19 and 20, the fetal thyroids of alcohol-exposed fetuses weighed significantly less than those of the two control groups, but more than the control thyroids 1 day earlier. Maternal alcohol consumption caused a significant decrease in both the follicular cell height and the follicle diameter of the fetal thyroid on all days examined. In the alcohol group on Days 19 and 20 of gestation, the cell height was less than, and the follicle diameter was approximately equal to those in the two controls 2 days earlier. These results indicate that, as a consequence of maternal alcohol consumption, growth of the fetal thyroid gland is retarded, and there are indications of fetal hypothyroidism, as seen from the histometric data. This latter is suggestive of a retarded thyrotropic activity of the fetal pituitary gland.     

The effects of nutrition on the reproductive performance of Finn x Dorset ewes. I. Plasma progesterone and LH concentrations during late pregnancy.

Progesterone and LH concentrations were measured in the plasma of blood samples taken from forty-eight pregnant ewes on Days 100, 120 and 134 of gestation. The ewes, in two groups of twenty-four were maintained from Day 100 until parturition on two planes of nutrition which supplied daily energy and protein intakes of about 4-1 or 2-3 Mcal metabolizable energy and either 192 or 111 g digestible crude protein per ewe. Within the groups, the ewes carried one, two or three fetuses and the feed intake was adjusted according to litter size to produce a uniform nutritional state within the group. On Day 100, litter size affected the concentration of plasma progesterone (P less than 0-001), but had no effect on Days 120 or 134 when the ewes were fed according to litter size. The low feed intake however caused a significant increase in plasma progesterone concentrations. The LH concentrations showed no major changes during late pregnancy and no effect of nutrition or little size on the plasma hormone concentration was observed. It was concluded that the effect of litter size on plasma progesterone concentration recorded on Day 100 or gestation was partly mediated by level of nutrition.     

Analysis of metopirone-induced hypertrophy of adrenals in fetal rats encephalectomized in utero

Pregnant rats were treated with 30 mg metopirone (M) each day for 2 days and autopsied on the third day in various gestational periods (Days 18-20, 19-21, and 20-22). Control rats were treated with saline alone (S). The adrenals of intact fetuses in M-treated dams were significantly heavier than those of intact fetuses in S-treated dams in every experimental period. In both M- and S-treated dams, the adrenals of encephalectomized (E) fetuses were lighter than those of intact littermates. However, in the experimental period of Days 18-20 and 19-21, the adrenals of E fetuses in M-treated dams were slightly but significantly heavier than those of similar E fetuses in S-treated dams. In contrast, in the experimental period Days 20-22, there was no significant difference in the weight of adrenals of E fetuses of M- and S-treated dams. These changes in fetal adrenal weight were reflected histologically in parallel changes in the size of adrenocortical cells. The observations suggest that the fetal adrenal hypertrophy following maternal treatment with metopirone can occur to some extent independent of the fetal brain, but that close to the end of gestation the hypertrophy occurs completely under the control of the fetal brain.     

Maternal serum progesterone concentration during pregnancy and lamb birth weight at parturition in Javanese Thin-Tail ewes with different litter sizes

Pregnant ewes, (N=38), with similar body weight and age (19, 13 and 6 carrying 1, 2 and 3 fetuses, respectively) were used to study the relationship between maternal serum progesterone concentration during pregnancy and lamb birth weight at parturition. Average maternal serum progesterone concentration in the ewes carrying 1, 2, and 3 fetuses was: 5.3±0.3, 6.2±0.7 and 6.6±0.5 ng/ml, during weeks 0 to 7 of gestation; 16.9±1.4, 25.3±1.5, and 26.8±2.5 ng/ml, during weeks 8 to 20; and 13.2±1.0, 18.7±1.0, and 19.8±1.7 ng/ml, during the entire gestation period respectively. Total lamb birth weight in ewes carrying 1, 2, and 3 fetuses was 1.9±0.1, 3.2±0.2, and 4.2±0.4 kg, respectively. In the respective litter sizes, ewes with higher mean serum progesterone concentration during the whole pregnancy gave birth to lambs with higher birth weight (r²=0.76, 0.42 and 0.46, for ewes carrying 1, 2 and 3 fetuses, respectively). The results of the study indicated that prenatal growth could probably be improved by increasing endogenous secretion of maternal progesterone during pregnancy.     

Distal air space epithelial fluid clearance in near-term rat fetuses is fast and requires endogenous catecholamines

Knowledge about the conversion of the epithelium in the distal air spaces of the lung from secretion to absorption is imperative to the understanding of postnatal lung development; little such information is available in rats. Distal air space fluid clearance was therefore measured in 21- to 22-day gestation rat fetuses and newborn (40 h) rats. Distal air space fluid clearance was measured from the increase in (131)I-albumin concentration in an isosmolar, physiological solution instilled into the developing lungs. There was no net fluid movement across the distal air space epithelium in the lungs of 21-day gestation fetuses. Twenty-four hours later, distal air space fluid was cleared at a rapid rate in the 22-day gestation fetuses. Within the first 40 h after birth, the rate rapidly declined to adult levels. The high distal air space fluid clearance at 22 days gestation and at 40 h after birth was mediated by beta-adrenergic receptors as demonstrated by elevated plasma epinephrine levels and inhibition by propranolol. Interestingly, the elevated distal air space fluid clearance in the 22-day gestation fetuses was only minimally amiloride sensitive; however, amiloride sensitivity increased over the first 40 h after birth. In conclusion, these studies demonstrate that 1) rapid rates of net alveolar fluid clearance occur late in gestation in the rat and 2) this clearance is driven by elevations of endogenous epinephrine.