Advancement of reproductive senescence and changes in the early expression of estrogen, progesterone and micro-opioid receptors induced by neonatal hypoxia in the female rat.
Perinatal hypoxia is a frequent birth complication, and although its early consequences on brain development have been well studied, few studies address any long-term effects. Postnatal insults producing small disturbances in endocrine function can have marked and long-lasting effects. In the present work we studied the effects of two types of perinatal brain injury: global hypoxia (H, 6.5% O2 for 50 min) and hypoxia plus ischemia (HI, ligature of the right carotid artery) on female rat reproductive performance and expression of mediobasal hypothalamus-preoptic area (MBH-PO) estrogen, progesterone and micro-opioid receptors at different times after injury, measuring the mRNA (by semiquantitative RT-PCR) and protein (by Western blot). H or HI advanced approximately 3 months after the appearance of blunted preovulatory LH surges and cyclic irregularities (prolonged estrus) characteristic of the early stages of reproductive senescence. 48 h after H or HI we observed decreases in ERbeta, microOR and PR (only in the H group) mRNAs and in total ER and microOR proteins, followed by increased PR levels (mRNA and protein) 7 days post-injury and by increased microOR protein and ERbeta mRNA in the H group and ERalpha, ERbeta and microOR mRNAs and ER protein in the HI group 30 days post-injury. Thus, an episode of hypoxia suffered during early postnatal life induces premature reproductive senescence on the female rats, accompanied by early changes in some MBH-PO hormone receptors (microOR, ER and PR), whose expression is intimately involved in the regulation of gonadotropin secretion and female sexual cyclicity.
Ezquer
Marcelo E
ME
Laboratorio de Reproducción y Lactancia, IMBECU-CRICYT-CONICET, C.C. 855, 5500 Mendoza, Argentina. mezquer@lab.cricyt.edu.ar
Valdez
Susana R
SR
Seltzer
Alicia M
AM
Jahn
Graciela A
GA
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D004967:Estrogens / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007839:Functional Laterality; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology; D011374:Progesterone / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism*; D012098:Reproduction / Q000502:physiology*
D004967:Estrogens; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D011374:Progesterone