Scholarlink

<p>Male reproductive health is declining globally, reflected by reduced sperm counts, impaired semen quality, increasing infertility, and a rising incidence of testicular cancer. Endocrine‑disrupting chemicals include metabolic disruptors, within which obesogens represent a specific subgroup that dysregulate lipid metabolism and cellular energy homeostasis and are increasingly implicated in these adverse trends. Although obesogens act across multiple tissues, their lipid‑metabolism‑related effects on testicular cells remain comparatively understudied. We investigated male reprotoxicity of an environmentally and human‑relevant organochlorine mixture (OC‑MIX), consisting of 20 persistent contaminants, including polychlorinated biphenyls (PCBs), chlordane, and dichlorodiphenyltrichloroethane/dichlorodiphenyldichloroethane (DDT/DDE), originally identified in ringed seal blubber and representative of Arctic food‑chain exposures. Although OC‑MIX has shown male reproductive toxicity in animal models, its cellular mechanisms in Sertoli cells remain insufficiently defined. Using immature murine Sertoli TM4 cells, we demonstrated that OC‑MIX (5–50&#xa0;µg/mL) disrupted lipid homeostasis and induced oxidative stress, culminating in lipotoxicity, processes known to compromise Sertoli cell support of spermatogenesis. These responses differed from those elicited by a fatty acid mixture or the lipotoxicant amiodarone and did not appear to involve androgen receptor, aryl hydrocarbon receptor, or peroxisome proliferator‑activated α signaling, suggesting distinct lipid‑centered mechanisms. Comparative profiling in immature murine Leydig TM3 cells revealed cell‑type‑specific responses, likely reflecting intrinsic differences in lipid composition. Notably, OC‑MIX selectively altered phospholipid and lysophospholipid species in Sertoli TM4 cells, indicating interference with membrane remodeling and lipid‑dependent signaling. Overall, these findings support the hypothesis that persistent organochlorines act as testicular obesogens, contributing to male reproductive dysfunction through selective, lipid‑disrupting mechanisms.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Lipid‑disrupting effects of an organochlorine mixture in Sertoli TM4 cells reveal testicular obesogen mechanisms

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月20日

查看全文
  • Ishita Virmani,
  • Eliška Sychrová,
  • Eliška Řehůřková,
  • Darshak Gadara,
  • Zdeněk Spáčil,
  • Iva Sovadinová

摘要

Male reproductive health is declining globally, reflected by reduced sperm counts, impaired semen quality, increasing infertility, and a rising incidence of testicular cancer. Endocrine‑disrupting chemicals include metabolic disruptors, within which obesogens represent a specific subgroup that dysregulate lipid metabolism and cellular energy homeostasis and are increasingly implicated in these adverse trends. Although obesogens act across multiple tissues, their lipid‑metabolism‑related effects on testicular cells remain comparatively understudied. We investigated male reprotoxicity of an environmentally and human‑relevant organochlorine mixture (OC‑MIX), consisting of 20 persistent contaminants, including polychlorinated biphenyls (PCBs), chlordane, and dichlorodiphenyltrichloroethane/dichlorodiphenyldichloroethane (DDT/DDE), originally identified in ringed seal blubber and representative of Arctic food‑chain exposures. Although OC‑MIX has shown male reproductive toxicity in animal models, its cellular mechanisms in Sertoli cells remain insufficiently defined. Using immature murine Sertoli TM4 cells, we demonstrated that OC‑MIX (5–50 µg/mL) disrupted lipid homeostasis and induced oxidative stress, culminating in lipotoxicity, processes known to compromise Sertoli cell support of spermatogenesis. These responses differed from those elicited by a fatty acid mixture or the lipotoxicant amiodarone and did not appear to involve androgen receptor, aryl hydrocarbon receptor, or peroxisome proliferator‑activated α signaling, suggesting distinct lipid‑centered mechanisms. Comparative profiling in immature murine Leydig TM3 cells revealed cell‑type‑specific responses, likely reflecting intrinsic differences in lipid composition. Notably, OC‑MIX selectively altered phospholipid and lysophospholipid species in Sertoli TM4 cells, indicating interference with membrane remodeling and lipid‑dependent signaling. Overall, these findings support the hypothesis that persistent organochlorines act as testicular obesogens, contributing to male reproductive dysfunction through selective, lipid‑disrupting mechanisms.