Adrenergic and Cholinergic Uterine Innervation and the Impact on Reproduction in Aged Women

Ioannis Kosmas, Antonio Malvası, Daniele Vergara, Ospan A. Mynbaev, Radmila Sparić, Andrea Tinelli
In: Current Pharmaceutical Design · 2020 · vol. 26(3) , pp. 358–362 · doi:10.2174/1381612826666200128092256 · PMID:32003664 · W3003306990
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⚙ AI-generated summary by claude@2026-06, 2026-06-10 ⓘ

Adrenergic and cholinergic nerve fiber distribution decreases with age in the human uterus, negatively impacting uterine physiology, pregnancy chance, and fetal development.

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⚙ AI-generated deep summary by claude@2026-07, 2026-07-09 · read from full text ⓘ

The paper examined uterine autonomic innervation by mapping adrenergic fibers and acetylcholine-related markers (including AChE-positive fibers) in the fundus, body, and cervix, using immunohistochemical approaches in young women and comparing these distributions with uterine tissue from aged/peri- or post-menopausal women. It reports that adrenergic and AChE neurofibers progressively decrease with increasing age, and that these fibers are closely associated with uterine arteries and myometrial smooth muscle, with markedly reduced neurotransmitter-related elements in older women. The authors link this decline to negative impacts on uterine physiology, including reduced pregnancy chance, reduced uterine growth, and increased abortion risk and prematurity. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

In recent years, the development of Assisted Reproductive Technique, the egg and embryo donation changed substantially the role of the uterus in recent years. It provided a higher chance for a pregnancy even in women over 45 years or post-menopause. In fact, the number of aged patients and in peri/post-menopause in pregnancy is nowadays increasing, but it increases obstetrical and neonatal related problems. The human uterus is richly innervated and modified especially during pregnancy and labor, and it is endowed with different sensory, parasympathetic, sympathetic and peptidergic neurofibers. They are differently distributed in uterine fundus, body and cervix, and they are mainly observed in the stroma and around arterial vessel walls in the myometrial and endometrial layers. Many neurotransmitters playing important roles in reproductive physiology are released after stimulation by adrenergic or cholinergic nerve fibers (the so called sympathetic/parasympathetic co-transmission). Immunohistochemical study demonstrated the localization and quantitative distribution of neurofibers in the fundus, the body and cervix of young women of childbearing age. Adrenergic and cholinergic effects of the autonomous nervous system are the most implicated in the uterine functionality. In such aged women, the Adrenergic and AChE neurofibers distribution in the fundus, body and cervix is progressively reduced by increasing age. Adrenergic and AChE neurotransmitters were closely associated with the uterine arteries and myometrial smooth muscles, and they reduced markedly by ageing. The Adrenergic and AChE neurofibers decreasing has a dramatical and negative impact on uterine physiology, as the reduction of pregnancy chance and uterine growth, and the increase of abortion risk and prematurity.
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Abstract

In recent years, the development of Assisted Reproductive Technique, the egg and embryo donation changed substantially the role of the uterus in recent years. It provided a higher chance for a pregnancy even in women over 45 years or post-menopause. In fact, the number of aged patients and in peri/post-menopause in pregnancy is nowadays increasing, but it increases obstetrical and neonatal related problems. The human uterus is richly innervated and modified especially during pregnancy and labor, and it is endowed with different sensory, parasympathetic, sympathetic and peptidergic neurofibers. They are differently distributed in uterine fundus, body and cervix, and they are mainly observed in the stroma and around arterial vessel walls in the myometrial and endometrial layers. Many neurotransmitters playing important roles in reproductive physiology are released after stimulation by adrenergic or cholinergic nerve fibers (the so called sympathetic/parasympathetic co-transmission). Immunohistochemical study demonstrated the localization and quantitative distribution of neurofibers in the fundus, the body and cervix of young women of childbearing age. Adrenergic and cholinergic effects of the autonomous nervous system are the most implicated in the uterine functionality. In such aged women, the Adrenergic and AChE neurofibers distribution in the fundus, body and cervix is progressively reduced by increasing age. Adrenergic and AChE neurotransmitters were closely associated with the uterine arteries and myometrial smooth muscles, and they reduced markedly by ageing. The Adrenergic and AChE neurofibers decreasing has a dramatical and negative impact on uterine physiology, as the reduction of pregnancy chance and uterine growth, and the increase of abortion risk and prematurity.

Keywords

Adrenergic fibers, acetylcholine positive fibers, reproduction, pregnancy, fertility, assisted reproductive technique, abortion. [http://dx.doi.org/10.1016/0165-1838(96)00019-7] [PMID: 8832521] [http://dx.doi.org/10.1016/S0196-9781(00)00282-5] [PMID: 11072126] [http://dx.doi.org/10.2174/1389203717666160330105341] [PMID: 27063643] [http://dx.doi.org/10.1016/j.peptides.2010.10.034] [PMID: 21167238] [http://dx.doi.org/10.3109/09513590.2012.709682] [PMID: 22849656] [PMID: 13891409] [http://dx.doi.org/10.1093/humupd/dmq016] [PMID: 20551073] [http://dx.doi.org/10.1016/S2222-1808(13)60094-8] [http://dx.doi.org/10.1016/S0165-1838(98)00170-2] [PMID: 9935266] [http://dx.doi.org/10.2108/zsj.19.387] [PMID: 12130815] [http://dx.doi.org/10.1152/ajpheart.01016.2011] [PMID: 22210747] [http://dx.doi.org/10.1007/BF00163817] [PMID: 8473200] [http://dx.doi.org/10.1177/002215540205000610] [PMID: 12019300] [http://dx.doi.org/10.1016/j.ejogrb.2005.07.020] [PMID: 16188372] [http://dx.doi.org/10.1177/002215540405201001] [PMID: 15385571] [PMID: 14672478] [PMID: 17039694]

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