title: In vivo blockade of acetylcholinesterase increases intraovarian acetylcholine and enhances follicular development and fertility in the rat.
abstract: Growth and differentiation of ovarian follicles are regulated by systemic and local factors, which may include acetylcholine (ACh). Granulosa cells (GCs) of growing follicles and luteal cells produce ACh and in cultured GCs it exerts trophic actions via muscarinic receptors. However, such actions were not studied in vivo. After having established that rat ovarian GCs and luteal cells express the ACh-metabolizing enzyme ACh esterase (AChE), we examined the consequences of local application of an AChE inhibitor, huperzine A (HupA), by osmotic minipump delivery into the ovarian bursa of hemiovariectomized rats. Saline was used in the control group. Local delivery of HupA for 4 weeks increased ovarian ACh content. Estrus cyclicity was not changed indicating a locally restricted range of HupA action. The number of primordial and primary follicles was unaffected, but small secondary follicles significantly increased in the HupA group. Furthermore, a significant increase in the number of corpora lutea suggested increased ovulatory events. In support, as shown upon mating, HupA-treated females had significantly increased implantation sites and more pups. Thus the data are in support of a trophic role of ACh in follicular development and ovulation and point to an important role of ACh in female fertility.
authors.affiliation: Laboratory of Neurobiochemistry, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, 8380492 Independencia, Santiago, Chile.
authors.forename: Javier
authors.initials: J
authors.lastname: Urra
authors.affiliation: BMC, Cell Biology, Anatomy III, Ludwig-Maximilian-University (LMU), 82152 Planegg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Blohberger
authors.affiliation: Laboratory of Neurobiochemistry, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, 8380492 Independencia, Santiago, Chile.
authors.forename: Michelle
authors.initials: M
authors.lastname: Tiszavari
authors.affiliation: BMC, Cell Biology, Anatomy III, Ludwig-Maximilian-University (LMU), 82152 Planegg, Germany.
authors.forename: Artur
authors.initials: A
authors.lastname: Mayerhofer
authors.affiliation: Laboratory of Neurobiochemistry, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, 8380492 Independencia, Santiago, Chile.
authors.forename: Hernan E
authors.initials: HE
authors.lastname: Lara
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000187:drug effects*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D005260:Female; D005298:Fertility / Q000187:drug effects*; D006080:Ovarian Follicle / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase; D000109:Acetylcholine