| Silver nanoparticles (Ag NPs) | Size: 20 and 200 nm Shape: - | Evaluation of cytotoxicity and genotoxicity of Ag NPs in testicular cells | Testicular cells (human) | 10 and 50 g/mL respectively | -Metabolic activity -Cell death -DNA damage | - Increased apoptosis, necrosis and decreased proliferation in a concentration and time-dependent manner | [10] |
| Size: 20 nm Shape: spherical | Evaluation toxicity effect of Ag NPs in somatic and germ cell | Somatic cell Sertoli cells Granulosa cells (mouse) | 0.5 and 1.0 mg/kg | -ROS production -Apoptosis -Histopathological studies | - Formation of autophagosomes and autolysosomes in Sertoli cells - Increased ROS production - Induced apoptosis - Increase in pro-inflammatory cytokines | [11] |
| Size: 50 nm Shape: spherical | Investigation of toxic effects of silver nanoparticles on reproductivetract of male mice | Sperm cells seminiferous tubules epithelial cells (mouse) | 10 mg/kg/bw | -Testicular weight -Sperm count and morphology -Seminiferous tubules epithelial cells histology | - Testicular weight loss - Increased number of dead and abnormal sperm -Decreased serum T as well as irregularity, deformity, atrophy, degeneration, and necrosis in seminiferous tubules epithelial cells. | [12] |
| Size: ~250 nm Shape: - | Evaluation of different concentrations of silver nanoparticles effects on sperm | Sperm cells (rat) | 30, 125 and 300 mg/kg | -Sperm parameters -Sperm chromatin integrity -Testicular histomorphometry | - Reduced sperm count, sperm viability - Altered sperm morphology at 300 mg/kg dose - Decreased the number of spermatogonia, Sertoli and Leydig cells at 300 and 125 mg/kg doses | [13] |
| Size: < 100 nm Shape: - | Investigation of intratesticular injection of Ag NPs on rat sperm parameters | Sperm cells (rat) | 220 μl of Ag NPs solution (0.46 mg Ag/mL) per testis | -Sperm motility -Sperm morphology -Sperm count | - Decreased sperm count and motility - Increased abnormal sperm | [14] |
| Size: 100 nm Shape: spherical | Evaluation of Ag NPs effects on the free radicals\' production, oxidant/antioxidant enzymes and sperm parameters | Sperm cells (rat) | 0, 10 and 50 mg/kg/bw | -Sperm parameters -LH, FSH and T hormones levels -Oxidant/antioxidant enzymes concentrations (MDA, SOD, CAT) | - Dose-dependent decrease in sperm motility, sperm velocity, kinetic parameters - Decrease in LH, FSH and T hormones - Increase in MDA and peroxide - Decrease in SOD, CAT, and GSH | [15] |
| Gold nanoparticles (Au NPs) | Size: 9 nm Shape: - | Investigation of Au NPs effects on human spermatozoon | Sperm cells (human) | - | -Sperm parameters | - Decreased sperm motility - Induced sperm fragmentation | [18] |
| Size: 1-100 nm Shape: - | Evaluation the effect of acute and chronic intravenous injection of Au NPs on sperm | Sperm cells (mouse) | 40 and 200 µg/kg/day | -Sperm parameters -DNA integrity | - Decrease in sperm count and motility depending on the dose and time - Increase in histone residues and DNA fragmentation | [19] |
| - | Examination of Au NPs reprotoxicity | Sperm cells (bovine) | 10 µg/mL | -Sperm parameters -Sperm function | - Reduced sperm motility - Decreased the ability of sperm to fertilize | [20] |
| Size: 5 nm Shape: - | Investigation of the effects of Au NPs on Leydig cellsand male reproductive function | TM3 Leydig cells (mouse) | 8.33, 25.00, and 62.50 µM (in vitro) 0.17 and 0.50 mg/kg/day (in vivo) | - Uptake - Cytotoxicity - T hormone production - Male reproductive function | - Induced autophagosomes - Increased ROS - Stopped the cell cycle in the S phase - Reduced testosterone - Increased the rate of epididymal sperm malformation without affecting fertility | [21] |
| Size: 2, 15, 50 nm Shape: - | Evaluation of the possible inhibitory effect of Au NPs onembryonic development | Embryo (mouse) | 2 μg Au/gram/bw | -Embryonic development | - Decreased expression of germ layer markers such as SOX1, SOX3, Nestin - Disturbed embryonic development in a size- and concentration-dependent manner | [22] |
| Copper nanoparticles (Cu NPs) | Size: 20–30 nm Shape: - | Evaluation of Cu NPs effects on the weight of some reproductive system organs and spermatozoa properties | Testis Epididymis Seminal vesicle Prostate gland Sperm cell (rat) | 20 and 40 mg/kg | -Reproductive system organs weight -Spermatozoa properties | - Decreased body weight - Increased sexual organs weight - Decreased sperm viability and normal sperm morphology in a concentration and time-dependent manner | [25] |
| Size: 40, 60 nm Shape: - | Investigation of the reproductive toxicity following oral administration of Cu NPs | Sperm cells (rat) | 1 and 2 mg/kg/day of 40 nm Cu NPs, 1 and 2 mg/kg/day of 60 nm Cu NPs | -Sperm density and motility -Sex hormone levels | - Decreased sperm density and motility - Decreased sex hormone (FSH, LH, T) levels | [26] |
| Size and shape: unsupported Cu NPs: spherical (2.88 nm) triangular (1.27 nm) hexagonal (1.81 nm) supported spherical Cu NPs by titanium, zeolite Y, and activated charcoal | Examination of the effect of morphology and support of Cu NPs on basic ovarian granulosa cell functions | ovarian granulosa cells (porcine) | 0, 1, 10, or 100 ng/mL | -Cell viability -Cell proliferation (PCNA accumulation) -Apoptosis (Bax protein accumulation) -Release of steroid hormones (Progesterone, T, and 17β-estradiol) | - Reduced cell viability by hexagonal Cu NPs, and increased by other Cu NPs - Decreased PCNA accumulation by unsupported spherical and hexagonal Cu NPs and spherical Cu NPs/titanium - Increased Apoptosis under Cu NPs/zeolite Y, and decreased under other Cu NPs - Inhibited the release of all steroid hormones by Cu NPs/titanium dioxide, but stimulated by Cu NPs/charcoal | [27] |
| Iron nanoparticles (Fe NPs) | PEI and PAA -coated iron nanoparticles (core size: 12 nm) | Evaluation of the Fe NPs with different surface charges effects on pregnant mice | (mouse) | 10 mg NPs/kg body mass | -Fetal death - Ability of NPs to cross the placenta -Fetal liver toxicity | - Positively charged PEI-coated nanoparticles increased post-implantation loss, reduced maternal weight, cross the placenta, and accumulated in the fetal liver | [30] |
| Size: 28 nm Shape: - | Investigation of short and long-term effects of positively and negatively charged Fe2O3NPs at low and high doses during the main organogenesis period | Uterine Testis Fetus (mouse) | 10 and 100 mg/kg | -Organogenesis -Tissue histology | - Favorable effects of low doses such as reducing fetal death and increasing litter size - Thickening of the endometrium and loss of germ cells by 100 mg/kg PEI-coated nanoparticles | [31] |
| Size: < 50 nm Shape: - | Evaluation of testicular toxicity effect of Fe2O3NPs | Testis (mouse) | 25 and 50 mg/kg/week | -ROS -Oxidant/antioxidant enzymes activity -Serum T level -Histopathological study | - Increased ROS, lipidperoxidation, protein carbonyl content, glutathione peroxidase activity, and nitric oxide levels - Decreased SOD, catalase, glutathione, and vitamin C - Increased Bax and caspase-3 expression - Increased Serum T levels - Vacuolization, detachment, and sloughing of germ cells | [32] |
| - | Examination of BSA-coated superparamagnetic Iron Oxide nanoparticles effect on granulosa cells | Granulosa cells (human) | 10, 25, or 50 μg/mL | -Steroid hormone receptor expression -Granulosa cell viability | - No effect was observed | [33] |
| Size: 5.3 nm Shape: - | Evaluation of bull sperm responseunder magnetic fluid containing DMSA-coated maghemite nanoparticles(MNP-DMSA) | Sperm (bull) | 0.03, 0.06, 0.015 mg/mL | -Sperm motility -Acrosome integrity -Cell membrane -Sperm structure -Uptake of nanoparticles | - No negative effects on motility, viability and sperm structure - Inability of nanoparticles to penetrate to the sperm | [34] |
| Size: 11 nm Shape: - | Investigation of uncoated, silica-coated, and PEGylated silica-coated iron nanoparticles effects on cultured ovarian tissue | Ovary Follicles (sheep) | 10 mg/mL | -Tissue morphological structure -Follicular viability -Oxidative stress -Particle permeability | - Reduced penetration of particles into cells by PEGylated nanoparticles - Induced oxidative stress by uncoated nanoparticles resulting in more tissue damage and follicular cells reduction | [35] |
| Zinc / Zinc oxide nanoparticles (Zn/ZnO NPs) | Size: < 100 nm Shape: - | In vivo evaluation of the possible protective role of ZnO NPs on testicular and epididymal structure and sperm parameters in nicotine-treated adult rats | Epididymis Sperm (rat) | 10 mg/Kg/day | - Testicular and epididymal histology -Sperm viability and morphology - Serum levels of FSH and LH hormones - Oxidative stress parameters - Steroidogenic enzymes expression | - Reduced oxidative stress - Increased steroidogenic enzymes expression - Improvement in the studied parameters | [36] |
| Size and shape: 70 nm, spherical Size and shape: 177 nm, spheroid orellipsoid Size: 30 nm | In vitro investigating the effect of ZnO NPs (in different concentrations and sizes) on male reproduction | Leydig cells Sertoli cells Spermatocytes (mouse) | 0, 5, 10, 15, 20 µg/mL 0, 0.04, 0.08, 0.4, 0.8, 4, 8, 16 µg/mL 0, 2, 3, 4, and 8 µg/mL | - ROS, GSH, and MDA level - Viability - Apoptosis -etc. | - Increased the levels of oxidant enzymes (such as MDA) - Decreased the levels of antioxidant enzymes (such as GSH) - Increased the production of ROS - Increased apoptotic proteins - Induction of apoptosis in sperm cells | [6, 42, 43] |
| Size: 30 nm Shape: - | In vivo examined the adverse effects of zinc oxide nanoparticles (ZnO -NPs) on the male reproductive system as well as their possible mechanism | Spermatozoa (mouse) | 50, 150, 450 mg/kg | - Sperm count - Serum testosterone levels - Apoptosis -Histopathological assay - Expression of genes associated with endoplasmic reticulum stress (IRE1α, XBP1s, BIP and CHOP) | - Histopathological damages such as germ cells atrophy and vacuolization - Decreased sperm count and serum testosterone levels along with increasing ZnO NPs dose - Increased expression of IRE1α, XBP1s, BIP and CHOP and caspase-3 | [44] |
| Size: 88 nm Shape: spherical | Investigation of the cytotoxic effects of ZnO NPs on spermatogonia cells with the aim of investigating cytoskeleton and nucleoskeleton changes | GC-1 cells (mouse) | 0, 1, 5, 8, 10, 20 µg/mL | - Cytoskeleton and nucleoskeleton changes - ROS production -DNA damage | - Toxicity of mouse spermatogonia under higher concentrations of ZnO NPs - Increase intracellular ROS, DNA damage - Cytoskeleton and nucleoskeleton modification | [45] |
| Size: 35 nm Shape: - | Evaluation of high and low doses of ZnO NPs effects on female reproduction | Ovary Ovarian follicles (mouse) | 20 and 150 μg/kg | - LH, FSH, estrogen and progesterone levels - Morphometric studies on ovaries and follicles | - The highest levels of LH and estrogen in the low dose ZnO NPs and the highest levels of progesterone in the high dose ZnO NPs. - Increased the diameter of the primordial follicles at high dose of ZnO NPs - Beneficial effects of low doses of ZnO on fertility improvement - Decrease fertility at high doses of ZnO NPs | [46] |
| - | In vitro investigation of the ZnO NPs (5, 15, 25 µg/ml) effects on the growth, ultrastructure and viability of ovarian antral follicles | Ovary Follicle (mouse) | 5, 15, 25 µg/mL | - Growth, ultrastructure and viability of ovarian antral follicles | - Decreased follicular diameter - Degradation of cytoskeletal arrangement - Ultrastructural changes such as incomplete transzonal projection and mitochondrial swelling | [47] |
| Nickel nanoparticles (Ni NPs) | Size: 90nm Shape: - | Investigation of the relationship between Ni NPs and reproductive toxicity | Ovary Epithelial cells of seminiferous tubules Epididymis Sperm (rat) | 5, 15, 45 mg/kg/day | -Sex hormone levels -Sperm motility - Histopathology - Reproductive outcome - apoptosis - etc. | - Increased FSH and LH levels in female - Decreased estradiol at doses 15 and 45 mg/kg/day - Ovarian lymphocytosis, vasodilation and contraction - Increased apoptotic cells in ovarian tissue -Changes in sperm motility - Decreased FSH and T levels in male - Epithelial cells shedding of seminiferous tubules | [49] |
| Size: 90 nm Shape: - | Evaluation of mechanisms involved in female reproductive toxicitycaused by Ni NPs | Ovary (rat) | 5, 15, 45 mg/kg/day | - Ovarian ultrastructural changes - ROS levels - Oxidant/antioxidant enzymes (SOD, CAT, MDA, NO) - Expression of apoptosis genes (caspase-3, caspase-8, caspase-9) and proteins (Fas, Cyt c, Bax, Bid, and Bcl-2) | - Swelling of mitochondria, loss of mitochondrial cristae, enlargement of endoplasmic reticulum - Decreased SOD and CAT activity - Increased ROS, MDA and NO levels - Decreased expression of caspases 3, 8, 9 mRNA - Increased expression of Fas, Cyt c, Bax, Bid proteins - Decreased Bcl-2 protein expression. | [50] |
| Titanium dioxide nanoparticles (TiO2 NPs) | - | In vitro study of nanoparticles effect on mouse testis Leydig cells | Leydig cells (mouse) | 0, 10, 100, 1000 µg/mL | - Leydig cells proliferation and vitality - Oxidative stress -Steroidogenesis | - Decrease in testis Leydig cells proliferative capacity and vitality - Increase in hemoxigenase-1 - Increase in StAR | [53] |
| - | In vivo evaluation of the TiO2NPs effects on male reproductive system | Sperm Germ cells (mouse) | 100 and 500 mg/kg | - Sperm density, motility, and morphology - Apoptosis - Level of gonadal hormones (T, E2) | High doses (500 mg/kg) of TiO2NPs caused to: - Reduced sperm density and motility - Increased abnormal sperm - Increased apoptosis in germ cells - Changed the level of gonadal hormones (T, E2) | [54] |
| Size: 40-60 nm Shape: rutile form | Structural and functional analysis of spermatogenic epithelium after exposure to TiO2NPs | Sperm Spermatogenic epithelium (rat) | - | -Immunohistochemical and morphometric characteristics of the spermatogenicepithelium | - Thinning, irregularity of layers, and non-attachment of sperm cells to the basement membrane - Decreased cell proliferation and differentiation | [55] |
| Size: 17 nm Shape: rutile form | Investigation of the airway exposure to TiO2NPs effects on sperm parameters and testosterone levels | Sperm (mouse) | 63 μg TiO2NPs/ week | - Sperm count - Testosterone level - Pneumonia | - Pneumonia was observed - No effect on testicular/ epididymal weight, sperm count, and serum testosterone levels | [56] |
| Size: 20-60 nm Shape: irregular & hemispherical | In vitro examination of the TiO2NPs genotoxic effects in sperm | Sperm (human) | 1 and 10 μg/L | - Genotoxicity - Genomic integrity - ROS - Oxidative stress | - Loss of sperm DNA integrity - Increased intracellular ROS levels | [57] |
| Size: ranged from 208 to 330 nm (mainly 294 nm) Shape: - | Evaluation of ovarian function and gene-expressed characteristics after long-term exposure to TiO2NPs | Ovary (mouse) | 10 mg/kg/day | - Fertility or pregnancy rate - Sex hormones- Gene-expressed profile - Oxidative stress | - Up-regulation of 223 genes and down-regulation of 65 ovarian genes - Increased expression of genes involved in the synthesis of estradiol such as CYP17A1 - Reduced the levels of progesterone, fertility and pregnancy rate - Increased oxidative stress | [58] |
| Size: ranged from 208 to 330 nm (mainly 294 nm) Shape: - | Investigation of female reproductive system function under TiO2NPs | Ovary Follicle (mouse) | 2.5, 5 and 10 mg/kg/day | - Fertility - Sex hormones levels -Body and ovarian weight | - Reduction in body weight and ovarian weight - Decreased the levels of sex hormones and the number of atretic follicles - Damaged the ovaries by increasing the expression of inflammation and follicular atresia cytokines - Decrease in fertility | [59] |
| Size: 25 nm Shape: - | Examination of the effect of different concentrations of TiO2NPs on follicular development and oocyte maturation | Follicle Oocyte (mouse) | 12.5, 25 and 50 µg/mL | - Follicular development - Oocyte maturation | - Reduced the number of viable follicles, the formation of antral follicles and the number of COCs | [60] |
| Size: 5-6 nm Shape: - | Investigation of POF after continuously exposing female mice to TiO2NPs | mouse | 2.5, 5, and 10 mg/kg | -Serum hormone levels (estradiol, progesterone, inhibin B, LH, FSH, FSH/LH ratio, AMH, TSH) -Autoimmune markers (fT3, fT4, TPO-Ab) | POF created due to: - decreased estradiol, progesterone, inhibin B - increased LH, FSH, FSH/LH ratio, AMH, TSH - Altered fT3, fT4, TPO-Ab | [61] |
| Size: 35 nm Shape: - | Evaluation of pregnancy complications under TiO2NPs | Uterus Fetus (mouse) | 0.8 mg/mouse | - Uterine weight - Fetal reabsorption | - Uterine weight loss - Increased fetal reabsorption | [62] |
| Size: 6.5 nm Shape: - | Investigation of the effects of TiO2NPs on fetal development | Placenta Fetus (mouse) | 25, 50, and 100 mg/kg bw | - Maternal weight - Placental and fetal weight - Live fetuses numbers - Fetal crown-rump and caudal length - Ossification | - Maternal, placental and fetal weight loss - Reduced number of live fetuses - Decreased crown-rump length and caudal length - Increased the number of dead fetuses or resorption - Inhibited fetal skeletal development | [63] |
| Size: < 25 nm Shape: - | Investigation of TiO2NPs effects on placentation during Gestational exposure | Placenta (mouse) | 1 and mg/kg/day | - Placental development - Placental apoptosis | - Disrupting the complex network of embryonic vessels - Inhibited proliferation - Nuclear pyknosis - Active caspase - Increased Bax proteins expression - Decreased Bcl-2 proteins expression | [64] |
| Cerium/Cerium oxide nanoparticles (Ce/CeO2 NPs) | Size: ~7 nm Shape: ellipsoidal | Investigation of very low and high doses of CeO2NPs effects on mice IVF | Sperm Oocyte (mouse) | 0.01 and 100 mg/L | - Fertilization - Genotoxicity | Very low doses of CeO2NPs caused to: - sperm and oocyte DNA damage - decreased fertilization - disruption of the interaction between gametes - induction of oxidative stress - no entry and accumulation of CeO2NPs in the cytoplasm of sperm, egg, and embryo, and only their accumulation around the sperm plasma membrane and oocyte ZP | [71] |
| Size: ~7 nm Shape: ellipsoidal crystallites | Investigation of CeO2NPs genotoxicity in male reproduction | Sperm (human) | 0.01 to 10 mg/L | - Genotoxicity | - CeO2NPs inability to enter sperm - Induced inversely dose-dependent damage to sperm DNA (very low doses of CeO2NPs led to genotoxicity) | [72] |
| Crystalline size: ~ 9 nm | In vitro investigation of CeO2NPs effects during IVM of oocytes on embryonic development | Oocyte Embryo (bovine) | 0, 44, 88, or 220 µg/ml | - Embryonic development - ROS - Apoptosis | Low doses of CeO2NPs (44 µg/mL) in the culture medium contributed to: - oocytes maturation with poor developmental capacity - improve the quality of embryos by increasing the number of ICM and trophectoderm cells - increase development of embryos up to the blastocyst stage - reduce the expression of apoptotic genes and stress responses | [73] |
| Size: 2-5 nm Shape: - | In vivo study of CeO2NPs effects on oocyte meiotic maturation and follicular granulosa cell viability in young and old mice | Oocyte Granulosa cells (mouse) | 45 mg/kg | - Oocyte maturation - Granulosa cells viability - ROS - Litter size | - Increase in the number of metaphases I and II oocytes within the follicles - Increase in the number of living granulosa cells - Decrease in necrotic or apoptotic granulosa cells - Protection of granulosa cells against oxidative stress in old mice by reducing the ROS content - Increase, the litter size in older mice | [74] |
| Size: ~ 3 nm Shape: - | In vitro study of interaction mechanisms between CeO2NPs and germ cells | Oocyte Follicles (mouse) | 2, 5, 10 and 100 mg/L | - Physicochemical transformation of CeO2NPs in culture medium - Ultrastructural interactions with follicular cells and oocytes - Genotoxic effects of CeO2NPs on follicles and oocytes | - CeO2NPs were able to enter and accumulate in follicular cells, while in oocytes they accumulated only around the ZP - DNA damage in follicular cells and dose-dependent damage to oocyte DNA | [75] |
| Size: < 10 nm Shape: - | Evaluation of CeO2NPs toxicity in the male reproductive system at different doses | Sperm Testis (mouse) | 0, 100, 200, and 300 μg/kg | - Sperm parameters - LH, FSH, T, and prolactin levels -Oxidant/antioxidant level | - Decrease in hemoglobin levels, PCV, and RBC count - Reduced testosterone level at 100 μg/kg doses and FSH, LH and prolactin levels at 200 μg/kg doses - Increased MDA enzyme levels - Decreased antioxidant enzymes activity - Decreased sperm count and motility - Increased abnormal sperm - Degeneration of seminiferous tubules | [76] |
| - | Investigation of the antioxidant properties of CeNPs at different doses | Sperm (rat) | 15 and 30 mg/kg/day | - Sperm parameters - Oxidative stress | - Improved the level of MDA - Protective effects on sperm by improving oxidative stress - Increased sperm count, motility, and viability at 30 mg/kg/day dose | [77] |
| Size: ~27 nm Shape: - | Evaluation of the effects of chronic administration of CeO2NPs in male reproductive system | Sperm (mouse) | 20 and 40 mg/kg | - Sperm parameters - Sperm DNA integrity - DSP - Blood T level - Testicular Ce element content - Steroidogenic enzymes levels - SF-1 gene/protein level | - Increased testicular Ce element content - Damaged sperm DNA - Reduced testicular weight, DSP, and sperm motility - Disrupted T synthesis by reducing the expression of steroidogenic enzymes and SF-1 | [78] |
| Size: < 25 nm Shape: - | Evaluation of the potential protective and antioxidant effects of CeNPs in Fipronil (FIP)-treated male rats | Testis (rat) | 35 mg/kg bw | -Lipid peroxidation - Apoptosis -Oxidant/antioxidant activity | - Reduced the harmful effects of FIP on testicular tissue - Reduced lipid peroxidation, apoptosis, and inflammation - Increased antioxidant activity | [79] |
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