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Thus, it can be postulated that<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h was created by nature roughly three billion years ago. Therefore, the wide expression of<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h in nature (i.e., in bacteria, archaea, unicellular organisms, plants, fungi, non\u2010vertebrates and vertebrates and in the abundance of non\u2010neuronal cells of mammals) is not surprising. The term non\u2010neuronal<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h and non\u2010neuronal cholinergic system have been introduced to describe the auto\u2010 and paracrine, that is, local regulatory actions of ACh in cells not innervated by neuronal cholinergic fibers and to communicate among themselves. In this way non\u2010neuronal<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h binds to the nicotinic or muscarinic receptors expressed on these local and migrating cells and modulates basic cells functions such as proliferation, differentiation, migration and the transport of ions and water. The present article is focused to the effects of non\u2010neuronal<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h linked to reproduction; data on the expression and function of the non\u2010neuronal cholinergic system in the following topics are summarized: (i) Sperm, granulosa cells, oocytes; (ii) Auxiliary systems (ovary, oviduct, placenta); (iii) Embryonic stem cells as first step for reproduction of a new individual after fertilization; (iv) Larval food as an example of reproduction in insects (honeybees) and adverse effects of the neonicotinoids, a class of world\u2010wide applied insecticides. The review article will show that non\u2010neuronal<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h is substantially involved in the regulation of reproduction in mammals and also non\u2010mammals like insects (honeybees). There is a need to learn more about this biological role of<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h. In particular, we have to consider that insecticides like the neonicotinoids, but also carbamates and organophosphorus pesticides, interfere with the non\u2010neuronal cholinergic system thus compromising for example the breeding of honeybees. But it is possible that other species may also be adversely affected as well, a mechanism which may contribute to the observed decline in biodiversity.<\/jats:p><jats:p><jats:bold>This is an article for the<\/jats:bold>\u00a0<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/journal\/10.1111\/(ISSN)1471-4159\/homepage\/special_issues.htm\">special issue XVth International Symposium on Cholinergic Mechanisms<\/jats:ext-link>.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13953-fig-0003-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13953","type":"journal-article","created":{"date-parts":[[2017,1,10]],"date-time":"2017-01-10T15:31:38Z","timestamp":1484062298000},"page":"144-150","source":"Crossref","is-referenced-by-count":42,"title":["Non\u2010neuronal acetylcholine involved in reproduction in mammals and honeybees"],"prefix":"10.1111","volume":"142","author":[{"given":"Ignaz Karl","family":"Wessler","sequence":"first","affiliation":[{"name":"Institute of Pathology University Medical Center Johannes Gutenberg University Mainz Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles James","family":"Kirkpatrick","sequence":"additional","affiliation":[{"name":"Institute of Pathology University Medical Center Johannes Gutenberg University Mainz Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,21]]},"reference":[{"key":"e_1_2_4_2_1","first-page":"235","article-title":"Acetylcholine synthesis and possible functions during sea urchin development","volume":"48","author":"Angelini C.","year":"2004","journal-title":"Eur. 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