{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T04:17:21Z","timestamp":1789186641271,"version":"build-2803163510"},"reference-count":79,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T00:00:00Z","timestamp":1721606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>D-Aspartic Acid (D-Asp) affects spermatogenesis by enhancing the biosynthesis of the sex steroid hormones acting either through the hypothalamus-pituitary\u2013testis axis or directly on Leydig cells. Recently, <jats:italic>in vitro<\/jats:italic> studies have also demonstrated the direct effects of D-Asp on the proliferation and\/or activity of germ cells. However, although D-Asp is present in Sertoli cells (SC), the specific role of the amino acid in these cells remains unknown. This study investigated the effects of D-Asp on the proliferation and activity of TM4 SC, focusing on the mitochondrial compartment and its association with the endoplasmic reticulum (ER). We found that D-Asp enhanced the proliferation and activity of TM4 cells as evidenced by the activation of ERK\/Akt\/PCNA pathway and the increase in the protein levels of the androgen receptor. Furthermore, D-Asp reduced both the oxidative stress and apoptotic process. An increase in mitochondrial functionality and dynamics, as well as a reduction in ER stress, were also found in D-Asp-treated TM4 cells. It is known that mitochondria are closely associated with ER to form the Mitochondrial-Associated Endoplasmic Reticulum Membranes (MAM), the site of calcium ions and lipid transfer from ER to the mitochondria, and <jats:italic>vice versa<\/jats:italic>. The data demonstrated that D-Asp induced stabilization of MAM in TM4 cells. In conclusion, this study is the first to demonstrate a direct effect of D-Asp on SC activity and to clarify the cellular\/molecular mechanism underlying these effects, suggesting that D-Asp could stimulate spermatogenesis by improving the efficiency of SC.<\/jats:p>","DOI":"10.3389\/fcell.2024.1438231","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T04:25:08Z","timestamp":1721622308000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Potential role of mitochondria and endoplasmic reticulum in the response elicited by D-aspartate in TM4 Sertoli cells"],"prefix":"10.3389","volume":"12","author":[{"given":"Sara","family":"Falvo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Grillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Latino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Chieffi Baccari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Maddalena","family":"Di Fiore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Venditti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Petito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Santillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.bbapap.2009.11.005","article-title":"Superoxide dismutases-A review of the metalassociated mechanistic variations","volume":"1804","author":"Abreu","year":"2010","journal-title":"Biochimica et Biophysica Acta\/General Subj."},{"key":"B2","doi-asserted-by":"publisher","first-page":"R163","DOI":"10.1530\/REP-13-0178","article-title":"Mitochondria functionality and sperm quality","volume":"146","author":"Amaral","year":"2013","journal-title":"Reprod."},{"key":"B3","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1111\/jmi.12133","article-title":"Cell-death assessment by fluorescent and nonfluorescent cytosolic and nuclear staining techniques","volume":"255","author":"Atale","year":"2014","journal-title":"J. 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