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.

Role of RFRP-3 in the development of cold stress-induced polycystic ovary phenotype in rats

“…Finally, RFRP-3 application to the ovary in vivo and in vitro influenced ovarian steroidogenesis. We have previously used the in vivo protocol to administer growth factors, antisense oligonucleotides, peptides such as kisspeptin or pharmacological blockers like huperzine (Lara et al 2000, Ricu et al 2008, Fernandois et al 2016, Urra et al 2016; thus, we are confident of the effectiveness of this procedure. The present results strengthen the concept that RFRP-3 exerts local paracrine control of ovarian steroid synthesis and release and furthermore suggests that RFRP-3 may be involved in the development of PCOS.…”

“…It is possible that the ovulatory response driven by RFRP-3 could be the result of an increased transition from secondary to antral follicles going to ovulation (both types of follicles were slightly decreased in number). The fact that RFRP-3 administration also partially rescued the effects of stress on development of secondary and antral follicles, and the stress effect on development of ovarian cysts, indicate a role for RFRP-3 in development of PCOS, but it is probable that this peptide is only part of a group of endocrine regulators of cyst formation, as per Dorfman et al (2003) and Urra et al (2016).…”

“…9) for RFRP-3 in terms of how it might influence the development of a polycystic phenotype in rats. Clearly, further experiments are necessary to determine how RFRP-3 interacts with other known modulators of PCOS (Dorfman et al 2003, Urra et al 2016.…”

ATP and Odor Mixture Activate TRPM5-Expressing Microvillous Cells and Potentially Induce Acetylcholine Release to Enhance Supporting Cell Endocytosis in Mouse Main Olfactory Epithelium

“…For example, adipose stem cells enhance myoblast proliferation via paracrine secretion of ACh (El-Habta et al, 2018 ). Granulosa cells and luteal cells in ovary release ACh to promote follicular development and female fertility (Mayerhofer and Fritz, 2002 ; Urra et al, 2016 ). In the carotid body, intrinsic release of ACh is used for intercellular coordinated chemical sensing (Kåhlin et al, 2014 ).…”

Developmental programming of the female neuroendocrine system by steroids

“…Organophosphorus pesticides (among which some of the most used are dichlorvos and chlorpyrifos) exert their toxicological action via inhibition of the enzyme acetylcholinesterase . This enzyme is expressed in several tissues, including the central nervous system and the ovary, and participates in the regulation of folliculogenesis . Thus, organophosphorus pesticides may affect not only the nervous system at brain level, but also the local ovarian system, although further research is needed to clarify this.…”