Huperzine‐A administration recovers rat ovary function after sympathetic stress

Riquelme, Raúl; Ruz, Freddy; Mayerhofer, Artur; Lara, Hernán E.

doi:10.1111/jne.12914

Cited by 6 publications

(5 citation statements)

References 49 publications

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“…This treatment elevated intraovarian ACh, increased numbers of healthy antral follicles, corpora lutea, and enhanced fertility success in female rats (Urra et al, 2016 ). These changes could conceivably be a direct consequence of higher intraovarian ACh levels and activation of cholinergic receptors in the ovary (Benitez et al, 2021 ; Riquelme et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…We found that HupA increased intraovarian ACh levels and changed ovarian follicular development, as evidenced by increased numbers of healthy antral follicles, corpora lutea, and enhanced fertility success in the rat (Urra et al, 2016 ). It appears possible that these changes are direct consequences of higher ACh levels and activation of specific cholinergic receptors in the ovary (Benitez et al, 2021 ; Riquelme et al, 2020 ), thus the hypothesis to be tested is that ACh from local origin acts on ovarian follicles through muscarinic receptors present in ovarian cells of the follicle.…”

Section: Introductionmentioning

confidence: 99%

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Muscarinic receptors in the rat ovary are involved in follicular development but not in steroid secretion

Cuevas

Bastías

Alanis

et al. 2022

Physiological Reports

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Acetylcholine (ACh) may be involved in the regulation of ovarian functions. A previous systemic study in rats showed that a 4‐week, intrabursal local delivery of the ACh‐esterase blocker Huperzine‐A increased intraovarian ACh levels and changed ovarian follicular development, as evidenced by increased healthy antral follicle numbers and corpora lutea, as well as enhanced fertility. To further characterize the ovarian cholinergic system in the rat, we studied whether innervation may contribute to intraovarian ACh. We explored the cellular distribution of three muscarinic receptors (MRs; M1, M3, and M5), analyzed the involvement of MRs in ovarian steroidogenesis, and examined their roles in ovarian follicular development in normal conditions and in animals exposed to stressful conditions by employing the muscarinic antagonist, atropine. Denervation studies decreased ovarian norepinephrine, but ovarian ACh was not affected, evidencing a local, nonneuronal source of ACh. M1 was located on granulosa cells (GCs), especially in large antral follicles. M5 was associated with the ovarian vascular system and only traces of M3 were found. Ex vivo ovary organo‐typic incubations showed that the MR agonist Carbachol did not modify steroid production or expression of steroid biosynthetic enzymes. Intrabursal, in vivo application of atropine (an MR antagonist) for 4 weeks, however, increased atresia of the secondary follicles. The results support the existence of an intraovarian cholinergic system in the rat ovary, located mainly in follicular GCs, which is not involved in steroid production but rather via MRs exerts trophic functions and regulates follicular atresia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Muscarinic receptors in the rat ovary are involved in follicular development but not in steroid secretion

Cuevas

Bastías

Alanis

et al. 2022

Physiological Reports

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“…in which they demonstrated that the increase in ACh in a normal ovary induced an increase in ovulation and fertility. In addition this is a characteristic of ACh because it is able to reverse the PCO phenotype induced by cold stress in rats ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

“…If this is correct, we either can suggest that NGF acting on sympathetic nerves increases NE in the ovary by a direct effect of NGF or induced by stress ( 11 , 12 ) and can participates in the development of the PCO phenotype in rat. It probably acts increasing the ACh concentration whose participation in ovary physiology is just recently been considered ( 4 , 13 ); much less is know in pathological conditions such as the PCO phenotype in rat.…”

Section: Introductionmentioning

confidence: 99%

Nerve Growth Factor: A Dual Activator of Noradrenergic and Cholinergic Systems of the Rat Ovary

et al. 2021

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The functioning of the ovary is influenced by the autonomic system (sympathetic and cholinergic intraovarian system) which contributes to the regulation of steroid secretion, follicular development, and ovulation. There is no information on the primary signal that activates both systems. The nerve growth factor (NGF) was the first neurotrophic factor found to regulate ovarian noradrenergic neurons and the cholinergic neurons in the central nervous system. The aim of this study was to determine whether NGF is one of the participating neurotrophic factors in the activation of the sympathetic and cholinergic system of the ovary in vivo and its role in follicular development during normal or pathological states. The administration of estradiol valerate (a polycystic ovary [PCO] phenotype model) increased norepinephrine (NE) (through an NGF-dependent mechanism) and acetylcholine (ACh) levels. Intraovarian exposure of rats for 28 days to NGF (by means of an osmotic minipump) increased the expression of tyrosine hydroxylase and acetylcholinesterase (AChE, the enzyme that degrades ACh) without affecting enzyme activity but reduced ovarian ACh levels. In vitro exposure of the ovary to NGF (100 ng/ml for 3 h) increased both choline acetyl transferase and vesicular ACh transporter expression in the ovary, with no effect in ACh level. In vivo NGF led to an anovulatory condition with the appearance of follicular cysts and decreased number of corpora lutea (corresponding to noradrenergic activation). To determine whether the predominance of a NE-induced polycystic condition after NGF is responsible for the PCO phenotype, rats were exposed to an intraovarian administration of carbachol (100 μM), a muscarinic cholinergic agonist not degraded by AChE. Decreased the number of follicular cysts and increased the number of corpora lutea, reinforcing that cholinergic activity of the ovary participates in controlling its functions. Although NGF increased the biosynthetic capacity for ACh, it was not available to act in the ovary. Hence, NGF also regulates the ovarian cholinergic system, implying that NGF is the main regulator of the dual autonomic control. These findings highlight the need for research in the treatment of PCO syndrome by modification of locally produced ACh as an in vivo regulator of follicular development.

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“…Riquelme [ 51 ] showed that when ACh esterase was blocked in rats exposed to cold stress (4 °C for 3 h day for 28 days), ovarian levels of both NA and ACh were elevated, and fewer cysts and normal testosterone and estradiol plasma levels were found. In the present study, it was observed that the blockage of the cholinergic system by the administration of atropine to animals previously treated with EV increased the number of healthy follicles and decreased follicular atresia, as well as the number of cysts.…”

Section: Discussionmentioning

confidence: 99%

Participation of the Cholinergic System in the Development of Polycystic Ovary Syndrome

Linares¹,

Acuña²,

Rosas³

et al. 2021

Molecules

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In rats with polycystic ovary syndrome (PCOS) induced by injection of estradiol valerate (EV), unilateral or bilateral section of the vagus nerve restores ovulatory function in 75% of animals, suggesting that the vagus nerve participates in the development of PCOS. Since the vagus nerve is a mixed nerve through which mainly cholinergic-type information passes, the objective of the present study was to analyze whether acetylcholine (ACh) is involved in the development of PCOS. Ten-day-old rats were injected with 2.0 mg EV, and at 60 days of age, they were microinjected on the day of diestrus in the bursa of the left or right ovary with 100 or 700 mg/kg of ovarian weight atropine, a blocker of muscarinic receptors, and sacrificed for histopathological examination after the surgery. Animals with PCOS microinjected with 100 mg of atropine showed a lack of ovulation, lower serum concentrations of progesterone and testosterone, and cysts. Histology of the ovaries of animals microinjected with 700 mg of atropine showed corpus luteum and follicles at different stages of development, which was accompanied by a lower concentration of progesterone and testosterone. These results allow us to suggest that in animals with PCOS, ACh, which passes through parasympathetic innervation, is an important component in the persistence and development of the pathophysiology.

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Huperzine‐A administration recovers rat ovary function after sympathetic stress

Cited by 6 publications

References 49 publications

Muscarinic receptors in the rat ovary are involved in follicular development but not in steroid secretion

Muscarinic receptors in the rat ovary are involved in follicular development but not in steroid secretion

Nerve Growth Factor: A Dual Activator of Noradrenergic and Cholinergic Systems of the Rat Ovary

Participation of the Cholinergic System in the Development of Polycystic Ovary Syndrome

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