Effects of Estrogen on Fetal Rabbit Lung Maturation: Morphological and Biochemical Studies

Abstract

Summary17P-Estradiol (0.44 to 4.4 &kg) was intramuscularly administered to pregnant rabbits on day 25 or 26 of gestation, and the fetuses were delivered by cesarean section 24 hr later. On light microscopy, the lungs from the treated group had larger alveoli and thinner interalveolar septa than did those from the controls at the same gestational age. The 1umen:septa ratio was 0.62 + 0.06 in the control group and 0.88 + 0.05 in the treated group ( P < 0.01). Blood vessels in the lungs of the treated group were also more mature than were those in the control group. Alveolar epithelial cells consisted of 52% undifferentiated, 21% type 11, and 27% type I cells in the control group. In the estrogen-treated group, the corresponding distribution was 25, 29, and 45%. There were 0.82 -+ 0.16 lamellar bodies per alveolar cell in the treated group compared to 0.38 k 0.06 in the controls (P < 0.05). Estrogen decreased fetal lung glycogen content from 247 + 15 pg/mg protein to 70 9 on day 26 and from 103 -+ 13 to 13 + 2 on day 27 ( P < 0.001). Estrogen administration increased the rate of incdrporation of choliie into phosphatidylcholine in fetal lung slices. decreased the rate of thymidine incorporation into DNA, but had no effect on the rates bf incorporatibn of ethanolamine into phosphatidylethanolamine or of leucine into protein. These data indicate that estrogen accelerates the rate of fetal lung maturation. It appears to stimulate lung differentiation at the expense of lung growth. SpeculationEstrogen may be involved in the physiologic control of fetal lung maturation and pulmonary surfactant production.We have previously shown that administration of 17/3-estradiol to pregnant rabbits at 25 to 26 days gestation (term is 31 days) accelerates fetal lung maturation and stimulates production of pulmonary surfactant (16,17). Thus, maternal estrogen administration has the following effects on the fetal lung: it increases the amount of total phospholipid and phosphatidylcholine as well as the phosphatidylcholine:sphingomyelin ratio in lung lavage (17), it increases the rate of choline incorporation into phosphatidylcholine in lung slices (16), and it increases the activities of pulmonary cholinephosphate cytidylyltransferase and lysolecithin acyltransferase (16), enzymes involved in the synthesis of total and disaturated phosphatidylcholine, respectively (33). Gross et al. (12) reported that estrogen accelerates maturation of fetal rat lung in organ culture. This fmding suggests that estrogen has a direct effect on the fetal lung.The purpose of the present study was to further characterize the effects of estrogen on fetal lung maturation. Inasmuch as there are distinct morphological changes during maturation of the fetal lung (2), we examined the effects of estrogen on these parameters of lung maturation. In addition, we determined the effect of estrogen on lung glycogen content because this decreases toward the end of gestation in a number of species (4,23,36), and it has been postulated that glycogen may provide substrate o...

Prenatal Estrogen and Progesterone Deprivation Impairs Alveolar Formation and Fluid Clearance in Newborn Piglets

“…More than 30 y ago, a single intramuscular injection of aqueous estrogens immediately after birth reduced the incidence of respiratory distress syndrome in premature infants in a randomized trial (10), possibly by improving their AFC (7) or surfactant production (9,28). Conversely, in cystic fibrosis, in which hyperactivity of Na ϩ absorption contributes to pathologic thickening of mucus (29), male sex is associated with a better prognosis (30), possibly because female sex hormones worsen (increase) the hyperactivity of Na ϩ absorption.…”

“…Administration of E2 to pregnant rabbits resulted in thinner alveolar septa and a higher proportion of differentiated alveolar cells (9). Postnatal administration of estrogen to preterm infants reduced the incidence of respiratory distress syndrome (10).…”

Hormonal basis for the gender difference in epidermal barrier formation in the fetal rat. Acceleration by estrogen and delay by testosterone.

“…Furthermore, glucocorticoids and thyroid hormone accelerate lung maturation (reviewed in reference 17), and, as we have shown, glucocorticoids accelerate epidermal barrier maturation in utero in the rat (18), and both glucocorticoids and thyroid hormone accelerate fetal rat barrier formation in vitro (19). Other hormones are also recognized to affect pulmonary development; for example, estrogen accelerates, while testosterone inhibits lung maturation (20)(21)(22)(23)(24)(25)(26). Additionally, a gender difference in the timing of lung maturational events has been noted, with males demonstrating a delay in lung development during late gestation (27)(28)(29)(30).…”

Estrogen-induced microvilli and microvillar channels and entrapment of surfactant-lipids by alveolar type I cells of bovine lung

“…Experiments in sheep have revealed a progressive rise in fetal plasma estrogen which achieves 13-fold increase to control levels in the range of 10 Ϫ9 M immediately before delivery (Rawlings and Ward, 1978). Estrogen in contrast to androgen, stimulates surfactant production (Thuresson-Klein, 1995;Khosla et al, 1981;Rooney, 1985). The endothelial cell line binds estrogen with high affinity and a high degree of specificity, which is inhibited by progesterone and to a small extent by testosterone (Colburn and Buonassisi, 1978).…”