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Al represented a considerable hazard to men\u2019s reproduction capabilities. Amygdalin (AMG) and <jats:italic>spirulina platensis<\/jats:italic> (SP) have been considered to have a strong antioxidant and repro-protective activity; also, targeted drug delivery systems called niosomes improve the distribution of water-soluble medications like amygdalin and spirulina. Current study targeted to determine the effectiveness of AMG and SP against negative reproductive impact resulted by aluminum chloride (AlCl<jats:sub>3<\/jats:sub>) toxicity. Sixty adult male albino rats were separated into 6 groups, including the control group, which received distilled water; AlCl<jats:sub>3<\/jats:sub> group, which received AlCl<jats:sub>3<\/jats:sub>; AMG+AlCl<jats:sub>3<\/jats:sub> group, which received AlCl<jats:sub>3<\/jats:sub>+AMG; AMGLN+AlCl<jats:sub>3<\/jats:sub> group, which received AlCl<jats:sub>3<\/jats:sub>+amygdalin-loaded niosomes; SP+AlCl<jats:sub>3<\/jats:sub> group, which received AlCl<jats:sub>3<\/jats:sub>+SP; and SPLN+AlCl<jats:sub>3<\/jats:sub> group, which received AlCl<jats:sub>3<\/jats:sub>+spirulina-loaded niosomes. All treatments were orally gavaged daily for 5 weeks, and rats were weighed weekly. At the termination of the experiment, some males (three from each group) were used for fertility traits via mating thirty virgin rat females (in a ratio of 1:2 and 2:3 male:female, respectively) followed by recording of birth weights and litter size (number of pups per each female) at birth to assess males\u2019 reproductive capability. Other males were euthanized for collection of serum, epididymal semen samples, and tissue samples for biochemical, sperm evaluation, gene expression, and histopathological measurements. There are a considerable number of negative impacts of AlCl<jats:sub>3<\/jats:sub> on male fertility clarified by declined serum testosterone levels; an increased oxidative stress (MDA, TAC); deteriorated semen quality; down-regulation of CYP11A1, StAR, and HSD-3b gene expressions; and testicular tissue degenerative changes. In addition, litter size (number of pups per each female) and birth weights of pups obtained from mated females were affected. AMG and SP treatments, either in niosomal or conventional form, alleviated the AlCl<jats:sub>3<\/jats:sub> negative effects by reducing oxidative stress; increasing testosterone levels; improving semen quality; upregulating of CYP11A1, StAR, and HSD-3b gene expressions; and reducing degenerative changes of testicular tissue. Besides, negative reproductive effect was diminished as observed by changes in the litter size (number of pups per each female) and birth weights of pups obtained from mated females. AMG and SP treatments (either in niosomal or conventional form), ameliorated the AlCl<jats:sub>3<\/jats:sub> negative effects as they possess powerful antioxidant activity, as well as they have the ability to improve the reproductive activity of affected males.<\/jats:p>\n                <jats:p><jats:bold>Graphical abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s00210-023-02788-9","type":"journal-article","created":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T07:02:22Z","timestamp":1698822142000},"page":"3211-3226","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Repro-protective activity of amygdalin and spirulina platensis in niosomes and conventional forms against aluminum chloride\u2013induced testicular challenge in adult rats: role of CYP11A1, StAR, and HSD-3B expressions"],"prefix":"10.1007","volume":"397","author":[{"given":"Fatma I.","family":"Abo El-Ela","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr","family":"Gamal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossny A.","family":"El-Banna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa A","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed H.","family":"El-Banna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdel-Razik H.","family":"Abdel-Razik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Abdel-Wahab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walid Hamdy","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa K.","family":"Abdelghany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,1]]},"reference":[{"issue":"3","key":"2788_CR1","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1208\/s12249-008-9105-1","volume":"9","author":"G Abdelbary","year":"2008","unstructured":"Abdelbary G, El-Gendy N (2008) Niosome-encapsulated gentamicin for ophthalmic controlled delivery. 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