Table 1.
Types of EDC and EDC-drugs mixtures reported to affect Sertoli cells.
| EDC/drug mixtures | Treatment type | Sertoli cell molecular/cellular changes; altered phenotypes | Citations |
|---|---|---|---|
| Cadmium and Diazinon (metal + insecticide) | 4 wk-old rats; In vivo; cadmium (30mg/L) and diazinon (40mg/L) in drinking water for 90 days | Adult Sertoli cell only phenotype in ST and exfoliation of germ cells likely due to damage to Sertoli cells and tight & adherent junctions disruption | Adamkovicova et al., (161) |
| Genistein and DEHP (phytoestrogen + phthalate plasticizer) | Rats; in utero exposure from GD14 to birth; gavage with GEN + DEHP mixture; each at 10 mg/kg/day | decreased Sertoli cell marker gene expression Amh and Wt-1 in PND120 adult rat testes | Jones et al., 2014 (162) |
| Genistein and phthalate DEHP | Rats; in utero exposure from GD14 to birth; gavage with DEHP alone or GEN + DEHP mixture; each at 10 mg/kg/day | caused decreased Sertoli cell marker Abp gene expression in PND6 juvenile rat testes | Jones et al., 2015 (163) |
| Genistein and phthalate DEHP | Rats; in utero exposure from GD14 to birth; gavage with GEN + DEHP mixtures at 0.1 or 10 mg/kg/day | In adult rat testes (PND120): altered morphology of seminiferous tubules. Increased rate of abnormal testicular phenotypes such as Sertoli-cell only; atrophied tubules; germ cell sloughing in lumen | Walker et al., (164) |
| DBP and Nonylphenol (NP) (Phthalate plasticizer + chemical used in industrial and consumer products) | In vitro; isolated primary Sertoli cells from 30 day-old Rat; mixtures of NP (range 0.01–50 µM) and MBP (range 10–20000 µM) | Additive effects on decreased cell viability of Sertoli cells, but no dramatic morphological changes | Li et al., (165) |
| DBP/MBP and Nonylphenol (NP) (phthalates + chemical used in industrial/consumer processes) | In vitro; isolated primary rat Sertoli cells from 9-day-old rats; NP (range 0.01–50 µM) and MBP (range 10–20000 µM). | Synergistic effect on viability and LDH leakage rate (plasma membrane integrity) at lower concentrations, but antagonistic efffect at higher concentrations. Testing 2 mathematical models based on the Loewe additivity (LA) theory and the Bliss independence (BI) theory. | Hu et al., (166) |
| DBP/MBP and Nonylphenol (NP) (phthalates + chemical used in industrial/consumer processes) |
In vitro; Sertoli cells isolated from 9-day-old rats; NP (0.1, 1, 10 mM), MBP (0.1, 1, 10 mM), NP + MBP (mixtures at same dose for both). In vivo: PND23–35 rats gavaged with DBP and NP as single or mixed compounds |
Disrupted structure/function of Sertoli cells and dysregulated hormone levels in serum by exposure to NP and DBP | Hu et al., (167) |
| Phthalate mixtures: Diethyl phthalate (DEP), diphenyl phthalate (DPP), and dimethyl isophthalate (DMIP) | In vitro: primary Sertoli cells isolated from 3-weeks old male mice. In vivo: 3-weeks-odl rats exposed by gavage for long-term (45 days) | In vitro exposures: Gene expression changes in mouse Sertoli cell markers transferrin, testin, occludin In vivo: decreased protein expression of 3β-HSD, connexin-43, and occludin after 45 days exposure. alteration of tight junctions, widening of intercellular space with phthalates. | Kumar et al., (168) |
| Anti-malaria insecticides: DDT, DDE, DM Industrial pollutant/plasticizer: NP Phytoestrogens: coumestrol, genistein | In utero, lactation, then direct exposure of rats up to PND104. exposure to a mixture of DDT, DDE and deltamethrin (DM) (35 mg/kg); to p-nonylphenol (p-NP) (2.5ug/kg); and phytoestrogens (2.5ug/kg) | Sertoli cell toxicity shown by thinner epithelium and reduced germ cell layers. Decreased Anogenital distance (AGD) | Patrick et al., (169) |
| Paracetamol mixed with EDCs: Estrogenic (BPA, 4-MBC, butyl paraben, OMC). Anti-androgenic: DBP, DEHP, vinclozolin, prochloraz, procymidone, linuron, pp’DDE, epoxiconazole | In utero; Rats; oral gavage from gestation (GD7-21), and lactation (PND 1-22), using 3 doses of total mixture (TotalMix100, 200, 450). Doses in (mg/kg/day). Mix of 4 estrogens (4-MBC) (6, 12, 27), (BPA (0.15; 0.3; 0.6) butyl paraben (6, 12, 27), octyl methoxycinnamate (OMC) (12, 24, 54). 8 anti-androgens: DBP, DEHP, vinclozolin, prochloraz, procymidone, linuron, pp’DDE, epoxiconazole (3 doses each; values between 1 and 9); paracetamol (80, 160, 360) | Delayed Sertoli cell maturation in adult testes. Some rats at PND300 showed Sertoli cell only phenotype in ST after exposure to EDCs i.e. DBP, DEHP, pesticides, and paracetamol mixtures. Paracetamol decreased sperm count | Axelstad et al., (170) |
| Fungicide mixtures: Carbendazim, Iprodione | Ex vivo; Pubertal (PND20-22) rats. seminiferous tubules (ST) cultured. Exposed to CBZ and IPR (50 nM each) alone or mixed, over 3-week period. | Sertoli cell markers Cx43 and Claudin-11 decreased protein expression in exposed STs. Altered Sertoli cell and germ cell populations | Durand et al., (171) |
| Fungicide mixtures: Triazole, imidazole fungicides | In vitro; Mouse immortalized immature Sertoli TM4 cell line | Inhibition of Sertoli cell proliferation, cell cycle arrest, mitochondrial dysfunction, ROS generation, glutathione depletion, apoptosis. | Petricca et al., (172) |
genistein, (GEN); di-2(ethylhexyl) phthalate, (DEHP); di(n-butyl) phthalate, (DBP); nonylphenol, (NP); mono-butyl phthalate, (MBP); 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane. (DDT).