title: Maternal sympathetic stress impairs follicular development and puberty of the offspring.
abstract: Chronic cold stress applied to adult rats activates ovarian sympathetic innervation and develops polycystic ovary (PCO) phenotype. The PCO syndrome in humans originates during early development and is expressed before or during puberty, which suggests that the condition derived from in utero exposure to neural- or metabolic-derived insults. We studied the effects of maternal sympathetic stress on the ovarian follicular development and on the onset of puberty of female offspring. Timed pregnant rats were exposed to chronic cold stress (4 °C, 3 h/daily from 1000 to 1300 h) during the entire pregnancy. Neonatal rats exposed to sympathetic stress during gestation had a lower number of primary, primordial, and secondary follicles in the ovary and a lower recruitment of primary and secondary follicles derived from the primordial follicular pool. The expression of the FSH receptor and response of the neonatal ovary to FSH were reduced. A decrease in nerve growth factor (NGF) mRNA was found without change in the low-affinity NGF receptor. The FSH-induced development of secondary follicles was decreased. At puberty, estradiol plasma levels decreased without changes in LH plasma levels. Puberty onset (as shown by the vaginal opening) was delayed. Ovarian norepinephrine (NE) was reduced; there was no change in its metabolite, 3-methoxy-4-hydroxyphenylglycol, in stressed rats and no change in NE turnover. The changes in ovarian NE in prepubertal rats stressed during gestation could represent a lower development of sympathetic nerves as a compensatory response to the chronically increased NE levels during gestation and hence participate in delaying reproductive performance in the rat.
authors.affiliation: Laboratory of NeurobiochemistryDepartment of Biochemistry and Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, 8380492 Independencia, Santiago ChileDepartamento de FisiologíaFacultad de Ciencias, Centro de Neurobiología y Plasticidad Cerebral (CNPC), Universidad de Valparaíso, 2360094 Valparaíso, ChileAnatomy III - Cell BiologyLudwig Maximilian University, Schillerstrasse 42 D-80336 Munich, Germany.
authors.forename: Rafael
authors.initials: R
authors.lastname: Barra
authors.affiliation: Laboratory of NeurobiochemistryDepartment of Biochemistry and Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, 8380492 Independencia, Santiago ChileDepartamento de FisiologíaFacultad de Ciencias, Centro de Neurobiología y Plasticidad Cerebral (CNPC), Universidad de Valparaíso, 2360094 Valparaíso, ChileAnatomy III - Cell BiologyLudwig Maximilian University, Schillerstrasse 42 D-80336 Munich, GermanyLaboratory of NeurobiochemistryDepartment of Biochemistry and Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, 8380492 Independencia, Santiago ChileDepartamento de FisiologíaFacultad de Ciencias, Centro de Neurobiología y Plasticidad Cerebral (CNPC), Universidad de Valparaíso, 2360094 Valparaíso, ChileAnatomy III - Cell BiologyLudwig Maximilian University, Schillerstrasse 42 D-80336 Munich, Germany.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Cruz
authors.affiliation: Laboratory of NeurobiochemistryDepartment of Biochemistry and Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, 8380492 Independencia, Santiago ChileDepartamento de FisiologíaFacultad de Ciencias, Centro de Neurobiología y Plasticidad Cerebral (CNPC), Universidad de Valparaíso, 2360094 Valparaíso, ChileAnatomy III - Cell BiologyLudwig Maximilian University, Schillerstrasse 42 D-80336 Munich, Germany.
authors.forename: Artur
authors.initials: A
authors.lastname: Mayerhofer
authors.affiliation: Laboratory of NeurobiochemistryDepartment of Biochemistry and Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, 8380492 Independencia, Santiago ChileDepartamento de FisiologíaFacultad de Ciencias, Centro de Neurobiología y Plasticidad Cerebral (CNPC), Universidad de Valparaíso, 2360094 Valparaíso, ChileAnatomy III - Cell BiologyLudwig Maximilian University, Schillerstrasse 42 D-80336 Munich, Germany.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Paredes
authors.affiliation: Laboratory of NeurobiochemistryDepartment of Biochemistry and Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, 8380492 Independencia, Santiago ChileDepartamento de FisiologíaFacultad de Ciencias, Centro de Neurobiología y Plasticidad Cerebral (CNPC), Universidad de Valparaíso, 2360094 Valparaíso, ChileAnatomy III - Cell BiologyLudwig Maximilian University, Schillerstrasse 42 D-80336 Munich, Germany hlara@ciq.uchile.cl.
authors.forename: Hernán E
authors.initials: HE
authors.lastname: Lara
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000097:blood; D030762:Estrous Cycle / Q000378:metabolism; D005260:Female; D007124:Immunoenzyme Techniques; D008425:Maternal Behavior; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D006080:Ovarian Follicle / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D011627:Puberty; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020800:Receptor, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012741:Sexual Maturation; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000473:pathology*; D014621:Vagina / Q000378:metabolism / Q000473:pathology*
chemical_list: D009414:Nerve Growth Factors; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D004958:Estradiol; D000242:Cyclic AMP; D009638:Norepinephrine