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Sex‐specific Effects of Nuclear and Membrane Progesterone Receptors on Breathing Stability in Newborn Rats
Author(s) -
Boukari Ryma,
Bairam Aida,
Joseph Vincent
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.727.7
Subject(s) - ventilation (architecture) , hypercapnia , receptor , respiratory center , endocrinology , medicine , hypoxia (environmental) , small interfering rna , respiratory system , plethysmograph , chemistry , biology , rna , biochemistry , gene , mechanical engineering , organic chemistry , oxygen , engineering
We tested the hypothesis that the nuclear (nPR) and membrane progesterone receptors α (mPRα) and β (mPRβ) have sex‐specific effects on respiratory control and breathing stability in newborn rats. The expression of nPR, mPRα or mPRβ in the brainstem region was attenuated by intracisternal injection of specific small interfering RNA (siRNA) to 10 days‐old male and female rats. An artificial cerebrospinal fluid was injected to the control animals. Twenty‐four hours after the injection, ventilation was recorded using whole body plethysmography during normoxia (21% O 2 , 50 min), hypoxia (12% O 2 , 5 min) and hypercapnia (5% CO 2 , 5 mim). The frequency of sighs and apneas was determined in normoxia and reported as events/hour. Treatments with siRNA against nPR, mPRα, or mPRβ had no effect on ventilation in normoxia, hypoxia, and hypercapnia. In male rats, the treatment with the siRNA against nPR had no effect on the frequency of sighs and apneas, while the treatment with the siRNA against mPRα increased the frequency of sighs (from 24±2 to 44±8, p=0.003) and the treatment with the siRNA against mPRβ increased the frequency of apneas (51±10 to 83±16, p=0.04). In female rats, the treatment with the siRNA against nPR increased the frequency of apneas (from 47±5 to 101±15, p=0.0003), but the treatment with the siRNAs against mPRα or mPRβ had no effect. We conclude that in newborn male rats mPRα and mPRβ, while in newborn female rats nPR contributes to breathing stability. These data could be useful to develop innovative approaches for pharmacological treatments of apnea of prematurity. Support or Funding Information Funded by CIHR (operating grants ‐ VJ, AB) and FRQ‐S (PhD fellowship ‐ RB).