The Effect of Fetal Thyroidectomy on Ovine Fetal Lung Maturation

Erenberg, Allen; Rhodes, Mitchell L.; Weinstein, Mary; Kennedy, Robert A.

doi:10.1203/00006450-197904000-00004

Cited by 57 publications

(17 citation statements)

References 4 publications

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“…Lines of evidence such as studies of Cunningham et al (27) and Erenberg et al (28), demonstrating delays in tracheal fluid lecithin/sphingomyelin ratios and retarded histologic lung maturation in thyroidectomized fetal sheep, do support the influence of thyroid hormone. The guinea pig does demonstrate an early Tj peak at 56 days, around the time of the major histologic progression of maturation, and a later peak at 59 days, preceding major changes in lung tissue DSPC and PG.…”

Section: Discussionmentioning

confidence: 94%

Lung Development in the Fetal Guinea Pig: Surfactant, Morphology, and Premature Viability

Sosenko

Frank

1987

Pediatr Res

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ABSTRACT. Guinea pigs demonstrate "precocious" physical and functional development, with newborns displaying open eyes, hair, self-feeding, and temperature regulation. In addition, morphologic lung development is precocious in the guinea pig, with advanced alveolarization taking place in utero. To explore whether pulmonary surfactant development is also advanced, and at what stage prematurely delivered guinea pigs are capable of survival, we delivered fetal guinea pigs at 2-to 3-day intervals from day 49 of gestation to day 69 (birth). These were examined for chronologic changes in lung morphology, lung tissue disaturated phosphatidylcholine, phosphatidylglycerol and glycogen content, and serum glucocorticoid and thyroid hormone levels. Other prematurely delivered guinea pigs were given brief postnatal resuscitation and their survival noted. We confirmed advanced morphologic lung maturation, yet found that surfactant development, with antecedent hormone peaks and glycogen depletion, occurs during the final 10-15% of gestation. Lung biochemical development is thus "on time" in the guinea pig, rather than "precocious" compared to other frequently studied laboratory animals. In addition, >50% of fetal guinea pigs are capable of survival by 8 days prior to term, well in advance of premature survivability in other small-sized species. The gestation period of the guinea pig is considerably longer (69 days) than that of other commonly studied small-sized mammals (i.e hamster -16 days, rat -22 days, rabbit -31 days). Associated with this relatively long gestation in the guinea pig is a remarkable degree of physical and functional maturity demonstrated by the newborn of the species. At birth guinea pigs have full coats of hair, open eyes, and the ability to regulate body temperature and to feed apart from the mother (1). Engel (2) hypothesized in 1953 that the lung growth and development of a species should parallel the overall development present at birth. In support of Engel's hypothesis, Lechner and Banchero (3) Received Oct. 2, 1986; accepted Dec. 4, 1986 found advanced morphologic lung development in the newborn guinea pig.We questioned whether other aspects of lung development, in addition to lung morphology, would also be accelerated in the developing guinea pig, adding further support to Engel's hypothesis. The present study was undertaken to investigate the following: I ) the developmental pattern of the surfactant system in the fetal guinea pig, 2) how surfactant development is chronologically related to morphologic development in the guinea pig lung, 3) whether an endogenous rise or peak in serum glucocorticoid and/or thyroid hormone levels precedes the maturational changes in lung morphology and/or surfactant. Finally, we sought to determine the viability of premature guinea pigs delivered at varying gestational ages, and what degree of lung morphologic and surfactant development would be associated with premature survival. METHODSTimed-pregnancy Camm-Hartley guinea pigs were obtained from Camm Laboratories, ...

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Section: Discussionmentioning

confidence: 94%

Lung Development in the Fetal Guinea Pig: Surfactant, Morphology, and Premature Viability

Sosenko

Frank

1987

Pediatr Res

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“…Since perinatal iodinated hormones increase pulmonary surfactant (Erenberg et al, 1979 ;Cunningham et al, 1980 ;Nwosu et al, 1980), intestinal maturation (Yeh et Moog, 1975Moog, , 1979Cabello et al, 1984), markedly influences thermoregulation (Cabello, 1983 ;Wrutniak and Cabello, 1986), and in young ruminants reduces intestinal E. coli adhesion (Cabello et al, , 1984, the thyroid hormone deficiency observed in this experiment could partly explain the high mortality rate recorved in hypotrophic lambs and underlined in the present work. En accord avec l'hypoglycémie et l'hyperurémie observées à la naissance chez l'agneau hypotrophique, la taille de la portée enregistrée dans les deux lots expérimentaux, et les travaux antérieurs du laboratoire, ce déficit hormonal pourrait être induit par une insuffisance placentaire.…”

Section: Resultsunclassified

Neonatal changes in plasma cortisol, free and total iodothyronine levels in control and hypotrophic lambs

Wrutniak¹,

Cabello²

1987

Reprod. Nutr. Dévelop.

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Summary. Neonatal changes in plasma free and total iodothyronines, cortisol, glucose and urea levels have been studied in 8 control (birthweight a 2.5 kg) and 16 hypotrophic lambs (birthweight < 2.5 kg) receiving limited amounts of colostrum during the first 36 h of life and then fed ad libitum. During the period of colostrum feeding, plasma glucose levels were low in both groups and increased after the onset of ad libitum feeding ; they were significantly lower in hypotrophic animals from birth to 36 h. Plasma urea levels increased during the period of colostrum feeding and decreased thereafter in all animals. At birth, they were significantly higher in hypotrophic lambs.Over the entire period studied (20 d), plasma levels of total T4, free T4, total T3 and free T3 were markedly lowered in hypotrophic lambs without alterations in the values of the T3/free T4 ratio. No differences could be observed in plasma reverse T3 and cortisol levels. For all blood parameters recorded, the neonatal changes were parallel in the two groups of lambs.In agreement with hypoglycemia and hyperuremia observed at birth in hypotrophic lambs, with the litter size recorded for each experimental group and with previous results, placental insufficiency linked to a large litter size gestation could be at the origin of low thyroid hormone levels.Introduction.

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“…Previous investigators have induced fetal or neonatal hypothyroidism by surgical or pharmacologic thyroidectomy to study the effect of T H deficiency on lung growth and maturation (15)(16)(17). Surgical thyroidectomy is stressful, cumbersome, and feasible only in large animals; it also leads to inadvertent parathyroidectomy.…”

Section: Discussionmentioning

confidence: 99%

Delayed Ultrastructural Lung Maturation in the Fetal and Newborn Hypothyroid (Hyt/Hyt) Mouse

et al. 1994

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Thyroid hormones influence fetal and neonatal lung showed a large amount of intracellular glycogen and fewer growth and maturation. However, the effect of naturally lamellar bodies in epithelial type I1 cells compared with occurring, genetically determined hypo-or hyperthy-Balb-c fetal mouse lungs. The neonatal hytlhyt mouse also roidism on fetal or neonatal lung maturation has not been showed signs of lung immaturity such as persistent epitheexamined. In the hythyt mouse, primary hypothyroidism, lial cell glycogen, few lamellar bodies, reduced disaturated which is characterized by a high serum TSH concentration, phosphatidylcholine content, and absent tubular myelin. is transmitted as an autosomal recessive trait. It occurs due We conclude that fetal and neonatal lung maturation is to a mutational defect in the P-subunit of the TSH receptor. delayed in the hytlhyt mouse with primary hypothyWe studied the lung ultrastructure of the fetal (18- Abbreviations and total phospholipid contents of newborn hythyt mouse TH, thyroid hormone lungs were determined. Male and female hythyt mice with T,, 3,5,3'-triiodothyronine a high serum TSH concentration were made euthyroid by EM, electron microscopy adding 3,5,3'-triiodothyronine to drinking water and then LB, lamellar body mated. Balb-c mice served as euthyroid controls. Fetal and TM, tubular myelin neonatal hythyt mice had a higher serum TSH concentra-TPL, total phospholipid tion than the Balb-c controls. Fetal hytlhyt mouse lungs DSPC, disaturated phosphatidylcholineTH are potent regulators of fetal and neonatal lung growth a n d maturation, whereas hypothyroidism is associated with a maturational delay (1, 2). Naturally occurring, genetically determined hypothyroidism in the mouse is a useful model for studying the effect of TH deficiency (3-8). In the hythyt mouse, primary hypothyroidism is transmitted a s an autosomal recessive trait and is due to a mutational abnormality in the TSH receptor (7). Adult and adolescent homozygous hytlhyt mice have small thyroid glands with a decreased number of follicles, very low serum TH concentration, and markedly elevated serum TSH activity (4-8). In this study, we have characterized the hypothyroid state and analyzed lung ultrastructure in the hythyt mouse fetus and 1-d-old pup and quantitated newborn lung DSPC and T P L content.-- METHODSAnimal care and euthanasia. The study protocol for the use of Balb hytlhyt and normal Balblc ( + I + ) mice was approved by the Animal Care Committee of St. Louis University. Care of these mice was in accord with the guidelines set by the National Institutes of Health. Our colony of genetically hypothyroid mice was established from two homozygous (hytlhyt) males and two heterozygous (hyt/+) females (Jackson Laboratories, Bar Harbor, ME). Mice were housed individually and allowed to eat food and drink water ad libitum. T o restore fertility, T, was added to the drinking water (0.2 kg/mL) of male mice. Homozygous mice could be separated easily from the heterozygous litter mates by -4 wk of age bec...

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The Effect of Fetal Thyroidectomy on Ovine Fetal Lung Maturation

Cited by 57 publications

References 4 publications

Lung Development in the Fetal Guinea Pig: Surfactant, Morphology, and Premature Viability

Lung Development in the Fetal Guinea Pig: Surfactant, Morphology, and Premature Viability

Neonatal changes in plasma cortisol, free and total iodothyronine levels in control and hypotrophic lambs

Delayed Ultrastructural Lung Maturation in the Fetal and Newborn Hypothyroid (Hyt/Hyt) Mouse

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