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

• Published in: Brain research Vol. 1214; pp. 73 - 83
• Main Authors: Ezquer, Marcelo E, Valdez, Susana R, Seltzer, Alicia M, Jahn, Graciela A
• Format: Journal Article
• Language: English
• Published: Netherlands 12-06-2008
• Subjects: Age Factors; Analysis of Variance; Animals; Animals, Newborn; Estrogens - genetics; Estrogens - metabolism; Female; Functional Laterality; Gene Expression Regulation, Developmental - physiology; Hypoxia - metabolism; Hypoxia - physiopathology; Ischemia - metabolism; Ischemia - physiopathology; Progesterone - genetics; Progesterone - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu - genetics; Receptors, Opioid, mu - metabolism; Reproduction - physiology; RNA, Messenger - metabolism
• ISSN: 0006-8993
• DOI: 10.1016/j.brainres.2008.03.029

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.