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DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Prenatal blockade of estradiol synthesis impairs respiratory and metabolic responses to hypoxia in newborn and adult rats

Department of Pediatrics, Laval University, Centre de Recherche (D0–711), Hôpital St-François d'Assise, Quebec, Quebec G1L 3L5, Canada

Submitted 27 October 2003 ; accepted in final form 7 May 2004

We tested the hypothesis that estradiol modifies respiratory control in pregnant rats and participates in the development of respiratory chemoreflexes in fetuses. Pregnant rats (n = 12) received daily subcutaneous injections of vehicle (Veh, n = 6) or 4-androsten-4-ol-3,17-dione acetate (ATD; inhibitor of estradiol synthesis; n = 6; 5 mg/day in vehicle) from gestational day 16 (G16) to delivery. Baseline ventilation (whole body plethysmography) and metabolic rate [oxygen consumption (O₂)] were determined at G14 and G20, in pups [on postnatal day 3 (P3) and P20] and in adult rats (on P70) born to Veh- or ATD-treated mothers. Hypoxic chemoreflex was assessed in P3 rats by acute exposure to 60% O₂ and in P20 or P70 rats by moderate hypoxia (12% O₂, 30 min). ATD treatment reduced circulating estradiol in pregnant dams at G20 without producing changes in the circulating level of estradiol precursors (testosterone and androstenedione). ATD-treated dams showed impaired respiratory adjustment to late gestation. Pups born to ATD mothers had higher resting O₂ (+23% at P3, +21% at P20), respiratory frequency (+15% at P3, +12% at P20), and minute ventilation (+11% at P3, +18% at P20) than pups from Veh mothers. Respiratory decrease during acute hyperoxic exposure at P3 was –9.7% in Veh (P < 0.05 vs. room air) and only –2.6% (P = not significant) in ATD pups. In P20 ATD rats, hypoxic ventilatory response was attenuated compared with Veh. In P20 and P70 rats, the drop of O₂ in hypoxia (–31% in P70, P < 0.0001) was not observed in ATD rats. We conclude that estradiol secreted during late gestation is necessary for respiratory adjustment to pregnancy and is required for adequate development of respiratory and metabolic control in the offspring.

hypoxic ventilatory response; prenatal estradiol synthesis; aromatase inhibitor; development

This article has been cited by other articles:

				D. Lumbroso and V. Joseph Impaired acclimatization to chronic hypoxia in adult male and female rats following neonatal hypoxia Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2009; 297(2): R421 - R427. [Abstract] [Full Text] [PDF]

				C. Julien, A. Bairam, and V. Joseph Chronic intermittent hypoxia reduces ventilatory long-term facilitation and enhances apnea frequency in newborn rats Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2008; 294(4): R1356 - R1366. [Abstract] [Full Text] [PDF]