{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T03:31:27Z","timestamp":1788233487455,"version":"build-2803163510"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:00:00Z","timestamp":1712102400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Grant","award":["2R01ES016591"],"award-info":[{"award-number":["2R01ES016591"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Peritubular macrophages (PTM\u03c6) are predominantly localized near spermatogonial stem cells in the testis. We previously revealed that exposure of peripubertal male Fischer rats to mono-(2-ethylhexyl) phthalate (MEHP) leads to increased PTM\u03c6s in the testis. The mechanisms that trigger increases in PTM\u03c6s in the testis are poorly understood. However, MEHP exposure is known to both induce spermatocyte apoptosis and to perturb the blood-testis barrier (BTB). This study aims to elucidate the association between the disruption of BTB and the increases of PTM\u03c6s in the testis by comparing the effects observed with MEHP to 2 other testicular toxicants with variable effects on the BTB and subtype of germ cell undergoing apoptosis. Methoxyacetic acid (MAA) acts directly on spermatocytes and does not affect BTB function, whereas cadmium chloride (CdCl2) induces profound injury to BTB. The results indicated that MAA exposure significantly increased spermatocyte apoptosis, whereas no significant changes in the numbers of PTM\u03c6s in the testis occurred. In contrast, CdCl2 exposure disrupted BTB function and increased the abundance of PTM\u03c6s in the testis. To further investigate whether MEHP-induced changes in BTB integrity accounted for the increase in PTM\u03c6s, a plasmid for LG3\/4\/5, the functional component of laminin-alpha 2, was overexpressed in the testis to stabilize BTB integrity before MEHP exposure. The results showed that LG3\/4\/5 overexpression substantially reduced the ability of MEHP to compromise BTB integrity and prevented the increase in PTM\u03c6 numbers after MEHP exposure. These results indicate that BTB disruption is necessary to increase PTM\u03c6s in the testis induced by toxicants.<\/jats:p>","DOI":"10.1093\/toxsci\/kfae043","type":"journal-article","created":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T22:14:27Z","timestamp":1712009667000},"page":"70-78","source":"Crossref","is-referenced-by-count":15,"title":["The blood-testis barrier disruption is a prerequisite for toxicant-induced peritubular macrophage increases in the testis of peripubertal rats"],"prefix":"10.1093","volume":"200","author":[{"given":"Xin","family":"Fang","sequence":"first","affiliation":[{"name":"Interdisciplinary Life Sciences Graduate Program, College of Pharmacy, The University of Texas at Austin , Austin, Texas 78712, USA"},{"name":"Center for Molecular Carcinogenesis and Toxicology, College of Pharmacy, The University of Texas at Austin , Austin, Texas 78712, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richa","family":"Tiwary","sequence":"additional","affiliation":[{"name":"Center for Molecular Carcinogenesis and Toxicology, College of Pharmacy, The University of Texas at Austin , Austin, Texas 78712, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian P","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Center for Molecular Carcinogenesis and Toxicology, College of Pharmacy, The University of Texas at Austin , Austin, Texas 78712, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6334-9777","authenticated-orcid":false,"given":"John H","family":"Richburg","sequence":"additional","affiliation":[{"name":"Center for Molecular Carcinogenesis and Toxicology, College of Pharmacy, The University of Texas at Austin , Austin, Texas 78712, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,4,2]]},"reference":[{"key":"2024062607522886400_kfae043-B1","doi-asserted-by":"crossref","first-page":"2733","DOI":"10.1074\/jbc.M005458200","article-title":"JAM-2, a novel immunoglobulin superfamily molecule, expressed by endothelial and lymphatic cells","volume":"276","author":"Aurrand-Lions","year":"2001","journal-title":"J. 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