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Sci.","Veterinary Sciences"],"abstract":"<jats:p>Heat stress (HS) impairs boar reproductive capacity via damaging Sertoli cells (SCs) and disrupting the integrity of the blood\u2013testis barrier (BTB). This present study investigated the protective effects and underlying molecular mechanisms of PTD-FNK against HS-induced injury in porcine SCs. A HS model (43 \u00b0C, 1 h) was established, and 0.1 nM was determined as the optimal working concentration of PTD-FNK. Results showed that PTD-FNK effectively reversed HS-induced BTB disruption by restoring the expression levels of tight junction proteins (Claudin-1, Occludin, ZO-1, and Cx43) to baseline levels (p &lt; 0.05). Concurrently, PTD-FNK alleviated HS-induced oxidative stress by enhancing total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity, while reducing malondialdehyde (MDA) content (p &lt; 0.05). It also suppressed HS-triggered apoptosis by downregulating the expression of pro-apoptotic proteins (Caspase-3\/8\/9 and Bax) and upregulating the anti-apoptotic protein Bcl-2 (p &lt; 0.05). Furthermore, PTD-FNK maintained cellular homeostasis by regulating mitochondrial dynamics\u2014restoring mitochondrial membrane potential (MMP) and balancing the expression of fusion-related protein Mfn1 and fission-related protein Drp1.Transcriptomic and LY294002 experiments confirmed PTD-FNK exerted effects via the PI3K\/AKT pathway, modulating ID3, H2AX, DDIT3, CDKN1C, RAD51, and TP53. Thus, PTD-FNK protects SCs from HS through multi-target regulation dependent on PI3K\/AKT, providing a novel strategy for boar reproductive health under HS.<\/jats:p>","DOI":"10.3390\/vetsci13080798","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T07:57:26Z","timestamp":1786521446000},"page":"798","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PTD-FNK Alleviated Heat Stress-Induced Apoptosis of Boar Sertoli Cells via the PI3K\/AKT Pathway"],"prefix":"10.3390","volume":"13","author":[{"given":"Qiuyan","family":"Huang","sequence":"first","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"},{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Provincial Key Laboratory of Animal Breeding and Nutrition, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiqi","family":"Ma","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Wang","sequence":"additional","affiliation":[{"name":"Animal Husbandry Research Institute, Guangxi Vocational University of Agriculture, Nanning 530001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Nanning Dabei Agricultural Feed Technology Co., Ltd., Nanning 530105, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixia","family":"Ji","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxing","family":"Song","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Li","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0355-6859","authenticated-orcid":false,"given":"Xiaoye","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sutian","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Provincial Key Laboratory of Animal Breeding and Nutrition, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanhuo","family":"Hu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1017\/S1751731111002448","article-title":"Adaptation to hot climate and strategies to alleviate heat stress in livestock production","volume":"6","author":"Renaudeau","year":"2012","journal-title":"Animal"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.2527\/jas.2012-5738","article-title":"The effects of heat stress and plane 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