Potential Reproductive Toxicity Research Articles

Podophyllotoxin Exposure Affects Organelle Distribution and Functions in Mouse Oocyte Meiosis.

Podophyllotoxin (POD) is one of the most characterized lignans that is commonly found in podophyllum, and its preparations and derivatives are widely used in clinical treatment due to strong antitumor and antivirus activities. POD has been reported for its neurotoxicity, liver toxicity, and potential reproductive toxicity. In the present study, we investigated the effects of POD on the organelles of mouse oocytes during meiosis. Our results showed that exposure to POD significantly reduced the developmental competence of mouse oocytes. Further analysis revealed that the endoplasmic reticulum (ER) failed to accumulate to the spindle periphery, suggesting that POD exposure might affect protein synthesis during oocyte meiotic maturation. Similarly, abnormal Golgi apparatus distribution was found after POD exposure, which could be confirmed by the aberrant localization of Rab11a-related vesicles, indicating that POD induced vesicle-based protein transport disorder. We also found the aberrant accumulation of lysosomes in the cytoplasm of POD-exposed oocytes, which implied that POD might lead to aberrant protein degradation. Moreover, the perinuclear distribution of mitochondria was also significantly disturbed, indicating the mitochondrial dysfunction after POD exposure. In all, our study illustrated that exposure to POD might disrupt protein synthesis, transport, degradation, and ATP production by its effects on the distribution and functions of organelles during mouse oocyte meiotic maturation.

Exposure to butylated hydroxytoluene compromises endometrial decidualization during early pregnancy

Butylated hydroxytoluene (BHT), one of the most widely used synthetic phenolic antioxidants, is a popular food additive. Previous studies have reported the possible health hazards of BHT. However, BHT effects on female reproduction, especially on endometrial decidualization, are still unknown. During early pregnancy, decidualization plays important roles for embryo implantation and pregnancy establishment. This study aimed to explore the effects of BHT on endometrial decidualization in pregnant mice. The pregnant mice received BHT via intraperitoneal injection at doses of 0, 200, and 400 mg/kg/day from day 1 (D1) of pregnancy until sacrifice. Under BHT exposure, maternal body weight was significantly decreased during early pregnancy. Compared with the control group, the number of implantation sites and uterine weight were significantly reduced in the BHT groups. The uterine lumen failed to close after BHT exposure, and the decidual morphology of endometrial stromal cells was inhibited by BHT. Furthermore, BHT significantly decreased the expression of endometrial decidual markers including COX2, HOXA10, and MMP9. Notably, the levels of serum estrogen (E2) and progesterone (P4) and expression levels of uterus estrogen receptor α (ERα) and progesterone receptor (PR) during early pregnancy were significantly upregulated following BHT exposure. In conclusion, these results demonstrated that gestational BHT exposure could inhibit decidualization of mouse endometrium during early pregnancy. The disorders of reproductive hormones and changes of hormone receptor signals could be responsible for the impaired decidualization. This study provided new evidence for the deleterious effects of BHT on female reproduction and revealed the potential reproductive toxicity of synthetic phenolic antioxidants.

Enhanced reproductive toxicities induced by phthalates contaminated microplastics in male mice (Mus musculus)

It has been demonstrated that microplastics (MPs) can transport phthalate esters (PAEs) into the tissues of mice. However, the influence of MPs on accumulation of PAEs and the combined toxicity need profound investigation. In this study, the bioaccumulation of PAEs and reproductive toxicity due to contaminated MPs exposure were investigated. After exposure to PAE-contaminated MPs for 30 days, significantly increased accumulation of PAE was observed in the liver and gut but not in the testis, which are ascribed to the distribution of MPs in tissues. Herein, most micro-size MPs accumulated in the gut and liver, while only a few nano-size MPs entered the Sertoli cells. Compared with virgin MPs and PAEs alone, PAE-contaminated MPs induced enhanced reproductive toxicities manifested by greater alterations in sperm physiology and spermatogenesis. The enhanced toxicities were also confirmed by the testicular transcriptomic alterations and aggravated oxidative stress induced by PAE-contaminated MPs. These aggravated reproductive toxicities were not caused solely by PAE, but may also be caused by the sensitization effect of oxidative stress induced by MPs. Our results highlight the potential reproductive toxicity on male terrestrial mammals due to co-exposure of MPs and plastic additives and provide valuable insights into the mechanism of combined toxicity of MPs and other pollutants.

Bisphenol AF induces apoptosis via estrogen receptor beta (ERβ) and ROS-ASK1-JNK MAPK pathway in human granulosa cell line KGN.

Bisphenol AF (BPAF) is an emerging environmental pollutant. Although BPAF is widely spread in the environment and human surroundings, its interference with ovarian function has not been fully elucidated. The aim of this study was to identify the mechanism underlying the effect of BPAF on the apoptosis of KGN cells, which maintain the physiological characteristics of ovarian granulosa cells. Our results indicated that BPAF induces KGN cell apoptosis in a concentration- and time-dependent manner. Meanwhile, BPAF exposure significantly promoted the expression of pro-apoptotic proteins, including Bax, Bid and Bak, while the expression of anti-apoptotic proteins, such as Bcl-2, Bcl-xL and Mcl-1, decreased significantly. We further detected a significant increase in intracellular ROS levels in response to high concentrations of BPAF exposure. After blocking the corresponding pathway, it was found that ROS mediates ASK1 and JNK activation. Furthermore, the role of Ca2+ overload and estrogen receptor β (ERβ) in BPAF-induced KGN cell apoptosis was also confirmed by using inhibitors. These results suggest that BPAF has potential reproductive toxicity for females, and ROS-ASK1-JNK axis may play a key role in BPAF-induced ovarian dysfunction. In addition, Ca2+ overload and ERβ pathway activation may also be an important mechanism of reproductive toxicity of BPAF.

The effects of the phthalate DiNP on reproduction†.

Di-isononyl phthalate (DiNP) is a high molecular weight, general purpose, plasticizer used primarily in the manufacture of polymers and consumer products. It can be metabolized rapidly and does not bioaccumulate. The primary metabolite of DiNP is monoisononyl-phthalate (MiNP) and the secondary metabolites include three oxidative derivatives of DiNP, which have been identified mainly in urine: mono-oxoisononyl phthalate (MOINP or oxo-MiNP), mono-carboxyisooctyl phthalate (MCIOP, MCOP or cx-MiNP), and mono-hydroxyisononyl phthalate (MHINP or OH-MiNP). The secondary metabolites are very sensitive biomarkers of DiNP exposure while primary metabolites are not. As the usage of DiNP worldwide increases, studies evaluating its potential reproductive toxicity are becoming more prevalent in the literature. In studies on female animals, the researchers found that the exposure to DiNP appears to induce negative effects on ovarian function and fertility in animal models. Whether or not DiNP has direct effects on the uterus is still controversial, and the effects on human reproduction require much more research. Studies on males indicate that DiNP exposure has disruptive effects on male reproduction and fertility. Occupational studies also indicate that the exposure to DiNP might induce negative effects on male reproduction, but larger cohort studies are needed to confirm this. This review presents an overview of the literature regarding the reproductive effects of exposure to DiNP.

Potential reproductive toxicity of multi-walled carbon nanotubes and their chronic exposure effects on the growth and development of Xenopus tropicalis

The increasing production and use of multi-walled carbon nanotubes (MWCNTs) will inevitably lead to discharge into the environment and exert negative effects on organisms. Many studies have focused on the toxicity of MWCNTs to aquatic animals, but little is known about their possible potential reproductive toxicity. In this study, 6 sexually mature Xenopus tropicalis were exposed to 0.5 and 2.5 mg/L MWCNTs suspensions for 56 days, and the toxicity of MWCNTs to the growth and reproduction of X. tropicalis were studied. The results showed that MWCNTs could inhibit the growth of body, including the testis, ovaries and fat of X. tropicalis. Histopathological section analysis showed that MWCNTs affected the formation of spermatogonia and oocytes, while had no notable effect on the heart or liver. MWCNTs would be accumulated in lungs of X. tropicalis inducing lung cannons. In addition, MWCNTs changed the microbial community structure and diversity of gut microbiota but did not change its abundance significantly. Moreover, MWCNTs could even decrease the fertilized and survival rate of X. tropicalis embryos. These results indicated that chronic exposure to MWCNTs would not only affect the growth and development of X. tropicalis, but also pose a potential risk on their reproduction.

The Causal Association Between Occupational, Environmental, and Lifestyle Factors and Reproductive Cancer Risk

A large number of synthetic chemicals are added into the environment during the last 3–4 decades due to industrial revolution and contemporary lifestyle adopted. Some are potential reproductive toxicants and might have teratogenic, mutagenic, or carcinogenic potential. Often occupational exposures are much higher than environmental exposures, thereby increasing incidence of reproductive cancer thought to be related to the exposure to persistent chemicals especially endocrine disruptors, compounded by lifestyle factors. The data suggests that exposure to some organochlorine compounds, ionizing, electromagnetic radiations, etc. and lifestyle factors (dietary and sexual practices) may have potential to induce cancer of reproductive organs with sparse evidence, and validating outcomes for such a relationship is also lacking. However, positive findings encourage avoiding such exposure and desisting from such lifestyle habits. There is a need to protect human beings from exposure to environmental/industrial chemicals by advocating not using them or replacing with less harmful/non-toxic chemicals and adopting healthy lifestyle.

Fetal Programming of Semen Quality (FEPOS) Cohort - A DNBC Male-Offspring Cohort.

BackgroundPrenatal exposures may contribute to male infertility in adult life, but large-scale epidemiological evidence is still lacking. The Fetal Programming of Semen quality (FEPOS) cohort was founded to provide means to examine if fetal exposures can interfere with fetal reproductive development and ultimately lead to reduced semen quality and reproductive hormone imbalances in young adult men.MethodsYoung adult men at least 18 years and 9 months of age born to women in the Danish National Birth Cohort living in relative proximity to Copenhagen or Aarhus and for whom a maternal blood sample and two maternal interviews during pregnancy were available were invited to FEPOS. Recruitment began in March 2017 and ended in December 2019. The participants answered a comprehensive questionnaire and underwent a physical examination where they delivered a semen, urine, and hair sample, measured their own testicular volume, and had blood drawn.ResultsIn total 21,623 sons fulfilled eligibility criteria of whom 5697 were invited and 1058 participated making the response rate 19%. Semen characteristics did not differ between sons from the Copenhagen and Aarhus clinics. When comparing the FEPOS semen parameters to similar cohorts, the median across all semen characteristics was slightly lower for FEPOS participants, although with smaller variation.ConclusionWith its 1058 young adult men, the FEPOS cohort is the largest population-based male-offspring cohort worldwide specifically designed to investigate prenatal determinants of semen quality. Wide-ranging information on maternal health, lifestyle, socioeconomic status, occupation, and serum concentrations of potential reproductive toxicants during pregnancy combined with biological markers of fertility in their sons collected after puberty allow for in-depth investigations of the ‘fetal origins of adult disease hypothesis’.

Reproductive effects of subchronic exposure to acetamiprid in male rats

Acetamiprid, a selective agonist of nicotinic acetylcholine recetors, is one of the most widely used neonicotinoids. There is limited data about toxicity of acetamiprid on male reproductive system. Therefore, the study aimed to investigate the reproductive toxic potential of acetamiprid in male rats orally treated with acetamiprid with low (12.5 mg/kg) medium (25 mg/kg) or high dose (35 mg/kg) for 90 days. According to our results, sperm concentration and plasma testosterone levels decreased in dose dependent manner. Gonadotropin-releasing hormone (GnRH), follicle-stimulating hormeone (FSH), luteinizing hormone (LH) levels increased at low and medium dose groups and acetamiprid caused lipid peroxidation and glutathione (GSH) depletion in the testes. Histologic examinations revealed that acetamiprid induced apoptosis in medium and high dose groups and proliferation index dramatically decreased in high dose group. In conclusion, acetamiprid caused toxicity on male reproductive system in the high dose. The mechanism of the toxic effect may be associated with oxidative stress, hormonal disruptions and apoptosis.

Two-generation reproduction and limited teratology studies of ethanamizuril fed to rats.

Ethanamizuril, a new anticoccidial agent that belongs to triazine derivatives, has a broad and good anticoccidial activity. To evaluate the reproductive toxicity and teratogenic potential of ethanamizuril, different concentrations of ethanamizuril were administered to Sprague-Dawley rats by feeding diets containing 0, 2, 8, and 30 ppm, respectively. Each group consisting of 30 males and 30 females (F0) was treated with different concentrations of ethanamizuril through a 13-week period before mating and during mating, gestation, parturition and lactation. In the 30 ppm dose group, pup body weight on days 7 and 21 in F1 offspring and day 21 in the F2a offspring were significantly decreased. A limited teratogenicity study was performed in combination with the F1 generation of a two-generation reproduction study. F1 offspring of the reproduction study were mated after weaning of the F2a offspring. Pregnant female rats were subjected to cesarean section on gestational day 20 for teratogenic examination. No obvious body weights, fetal body lengths, tail lengths, litter weights, number of viable fetuses, external, skeletal, or visceral malformations in fetuses were noted in any groups in the teratogenic test, but ethanamizuril could be passed on to offspring through lactation.

Multigenerational reproductive assessment of 4-methylimidazole administered in the diet to Hsd:Sprague Dawley SD rats

The general population, including children and adolescents, is exposed to 4-methylimidazole (4-MI) in the diet. 4-MI is a by-product of caramel color manufacturing. It has been previously classified as a possible human carcinogen and displays potential reproductive toxicity. A follow up assessment of reproductive toxicity was conducted in rats utilizing the reproductive assessment by continuous breeding paradigm, in which multiple generations were exposed to 4-MI in diet at 750, 2500, and 5000 ppm. 4-MI exposure was associated with delays in preputial separation and vaginal opening, impairment in reproductive performance, and concomitant histopathological findings in the prostate, testis, and epididymis at 2500 and 5000 ppm. The Lowest Observed Adverse Effect Level for reproductive (based on prostate atrophy) and developmental toxicity (based on delays in preputial separation and vaginal opening) was 750 ppm, equivalent to approximately 50−60 mg/kg bw/day.

Developing novel in silico prediction models for assessing chemical reproductive toxicity using the naïve Bayes classifier method.

Assessment of reproductive toxicity is one of the important safety considerations in drug development. Thus, in the present research, the naïve Bayes (NB)-classifier method was applied to develop binary classification models. Six important molecular descriptors for reproductive toxicity were selected by the genetic algorithm. Then, 110 classification models were developed using six molecular descriptors and10 types of fingerprints with 11 different maximum diameters. Among these established models, the model based on six molecular descriptors and the SciTegic extended-connectivity fingerprints with 20 maximum diameters (LCFC_20) displayed the best prediction performance for reproductive toxicity (NB-1), which gave a 0.884 receiver operating characteristic (ROC) score and 91.8% overall prediction accuracy for the Training Set, and produced a 0.888 ROC score and 83.0% overall accuracy for the external Test Set I. In addition, for the external rat multi-generation reproductive toxicity dataset (Test Set II), the NB-1 model generated a 0.806 ROC score and 85.1% concordance. The generated prediction results indicated that the NB-1 model could give robust and reliable predictions for a reproductive toxicity potential of chemicals. Thus, the established model could be applied to filter early-stage molecules for potential reproductive adverse effects. In addition, six important molecular descriptors and new structural alerts for reproductive toxicity were identified, which could help medicinal chemists rationally guide the optimization of lead compounds and select chemicals with the best prospects of being safe and effective.

Acute Damage to the Sperm Quality and Spermatogenesis in Male Mice Exposed to Curcumin-Loaded Nanoparticles.

BackgroundCurcumin has shown many pharmacological activities in both preclinical and clinical studies. Many technologies have been developed and applied to improve the solubility and bioavailability of curcumin, especially the nanotechnology-based delivery systems. However, there has been evidence that certain nanoparticles have potential reproductive toxicity in practice.MethodsCurcumin-poly (lactic-co-glycolic acid) (PLGA)-PEG nanoparticles (Cur-PLGA-NPs for short) were prepared. The Cur-PLGA-NPs were evaluated with its effect on the proliferation of mouse testicular cell lines in vitro and spermatogenesis in vivo, while PLGA-NPs were used as control. For animal experiments, male BALB/c mice were treated with 20 mg/kg of Cur-PLGA-NPs for continuous 10 days via tail vein injection.ResultsWe found the curcumin nanoparticles suppressed the proliferation of testicular cell lines in vitro. Furthermore, a short-term intravenous delivery of curcumin-loaded nanoparticles could be harmful to the differentiation of spermatogonia, the elongation of spermatids, as well as the motility of mature sperms.ConclusionIn the present study, we disclosed the acute damage on mouse spermatogenesis and sperm parameters by curcumin-loaded nanoparticles. Our results suggested that the reproductive toxicity of nanoformulated curcumin needs to be prudently evaluated before its application.

Value and limitation of structure-based profilers to characterize developmental and reproductive toxicity potential

The uncertainty regarding the safety of chemicals leaching from food packaging triggers attention. In silico models provide solutions for screening of these chemicals, since many are toxicologically uncharacterized. For hazard assessment, information on developmental and reproductive toxicity (DART) is needed. The possibility to apply in silico toxicology to identify and quantify DART alerts was investigated. Open-source models and profilers were applied to 195 packaging chemicals and analogues. An approach based on DART and estrogen receptor (ER) binding profilers and molecular docking was able to identify all except for one chemical with documented DART properties. Twenty percent of the chemicals in the database known to be negative in experimental studies were classified as positive. The scheme was then applied to 121 untested chemicals. Alerts were identified for sixteen of them, five being packaging substances, the others structural analogues. Read-across was then developed to translate alerts into quantitative toxicological values. They can be used to calculate margins of exposure (MoE), the size of which reflects safety concern. The application of this approach appears valuable for hazard characterization of toxicologically untested packaging migrants. It is an alternative to the use of default uncertainty factor (UF) applied to animal chronic toxicity value to handle absence of DART data in hazard characterization.

Rat two-generation reproductive toxicity and teratogenicity studies of a novel coccidiostat – Ethanamizuril

In the current study, to support the safety assessment of ethanamizuril as a new potent anticoccidial agent of triazine compounds, a reproductive toxicity and teratogenic potential assay of ethanamizuril was investigated. Groups of 30 males and 30 females were administered 0, 0.02, 0.1 or 0.2 mg/ml ethanamizuril by gastric incubation through a 10-week prebreed period as well as during mating, gestation, parturition and lactation in any generation. Compared to the control group, no test compound-related changes in copulation index, fertility index, gestation length, litter size, pup weight, pup sex ratio, pup viability, epididymal sperm counts or motility or other functional reproductive measures were noted in any generation, except few significant changes in high dose group in the number of sperm motility at III level in F0 males and the body weights of GD14 and GD21 in F1 rats. There were no compound-related necropsy findings or effects on organ weight. Histopathologic examinations revealed no evidence of compound-related changes in any organs including the reproductive organs of both sexes. In conclusion, long-term administrated 0.2, 1.0 and 2.0 mg/kg of ethanamizuril by means of oral gavage did not affect the reproduction of Sprague-Dawley rats and the development ability of their offspring under the experimental conditions.

The effects of di(2-ethylhexyl) phthalate exposure in women with polycystic ovary syndrome undergoing in vitro fertilization.

ObjectivesDi(2-ethylhexyl) phthalate (DEHP) is a common endocrine-disrupting chemical, which has potential reproductive toxicity. This study aimed to explore the effects of DEHP exposure in women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization.MethodsIn this case-control study, DEHP levels in follicular fluid (FF) of women with PCOS (n = 56) and controls (n = 51) were measured. The in vitro effects of DEHP exposure on primary-cultured human granulosa cells (GCs) and a steroidogenic human granulosa-like tumor cell line (KGN cells) were analyzed.ResultsConcentrations of DEHP in FF were significantly higher in women with PCOS than in controls. The clinical pregnancy rate was significantly lower in women with PCOS with high levels of DEHP than in controls. The levels of androgens produced by human GCs were significantly increased following DEHP exposure. Compared with controls, DEHP-treated human GCs and KGN cells showed significantly lower viability, cell cycle arrest, higher apoptosis, and altered expression of apoptosis-related genes.ConclusionWomen with PCOS are exposed to increased levels of DEHP in follicles, which may be associated with pregnancy loss following in vitro fertilization. DEHP may disrupt steroid production, balance in cellular proliferation, and apoptosis in human granulosa cells.

Transcriptomic analysis reveals potential mechanisms of toxicity in a combined exposure to dibutyl phthalate and diisobutyl phthalate in zebrafish (Danio rerio) ovary

Phthalate esters (PAEs), which are notable plasticizers, can be prolific contaminants in aquatic environments, and have been shown to induce reproductive toxicity. However, the studies concerning their toxicity towards aquatic species are based on individual chemicals, and the combined toxicity of PAEs to aquatic organisms remains unclear. The aim of this study was to explore the potential toxicity mechanisms associated with combined exposure to dibutyl phthalate (DBP) and diisobutyl phthalate (DiBP) in adult female zebrafish ovaries. Zebrafish were exposed to DBP, DiBP and their mixtures for 30 days, and their effects on ovarian histology, plasma sex hormones and ovarian transcriptomics were investigated. Plasma estradiol (E2) levels were significantly decreased by 38.9% in the DBP-1133 exposure group and 41.0% in the DiBP-1038 exposure group. The percentage of late/mature oocytes was also significantly decreased by 17.3% under DBP-1133 exposure and 16.2% under DiBP-1038 exposure, while that under combined exposure was not significantly affected. Nevertheless, transcriptome sequencing revealed 2564 differentially expressed genes (DEGs) in zebrafish ovaries after exposure to the mixtures. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the DEGs were involved in the neuroactive ligand-receptor interaction, GnRH, progesterone-mediated oocyte maturation, oocyte meiosis and steroid hormone biosynthesis signaling pathways. These results revealed that combined exposure exerts potential reproductive toxicity at the molecular level.

High-throughput COPAS assay for screening of developmental and reproductive toxicity of nanoparticles using the nematode Caenorhabditis elegans.

With the rapid advancement and numerous applications of engineered nanomaterials (ENMs) in science and technology, their effects on animal health, environment and safety should be considered carefully. However, quick assessment of their effects on developmental and reproductive health and an understanding of how they cause such adverse toxic effects remain challenging, because of the fast-growing number of ENMs and the limitations of the different toxicity assays currently in use as well as lack of suitable animal model systems. In this study, we performed a high-throughput complex object parametric analyzer and sorter (COPAS) assay for assessing the developmental and reproductive toxicity of ENMs using Caenorhabditis elegans and provide descriptions of the data and their subsequent analysis. The results showed significant reproductive and developmental toxicity potential of different ENMs. We assessed the usefulness of this method in terms of error-free data, user-friendliness and results being consistent with those of visual, molecular and cellular studies. Moreover, the COPAS Biosort system could be used on a larger scale to screen thousands of chemicals, drugs, pharmaceuticals and ENMs. This study also indicates that the COPAS-based high-throughput screening system is highly reliable for the assessment of toxicity and health risks of NMs.

Reproductive toxicity of manganese dioxide in forms of micro- and nanoparticles in male rats.

BackgroundManganese Dioxide (MnO) has long been used in industry, and its application has recently been increasing in the form of nanoparticle. Objective: The present study was an attempt to assess the effects of MnO nanoparticles on spermatogenesis in male rats.Materials and MethodsMicro- and nanoparticles of MnO were injected (100 mg/kg) subcutaneously to male Wistar rats (150 20 gr) once a week for a period of 4 weeks, and the vehicle group received only normal saline (each group included 8 rats). The effect of these particles on the bodyweight, number of sperms, spermatogonia, spermatocytes, diameter of seminiferous tubes, testosterone, estrogen, follicle stimulating factor, and the motility of sperms were evaluated and then compared among the control and vehicle groups as the criteria for spermatogenesis.ResultsThe results showed that a chronic injection of MnO nanoparticles caused a significant decrease in the number of sperms, spermatogonia, spermatocytes, diameter of seminiferous tubes (p 0.001) and in the motility of sperms. However, no significant difference was observed in the weight of prostate, epididymis, left testicle, estradiol (p = 0.8) and testosterone hormone (p = 0.2).ConclusionIt seems that the high oxidative power of both particles was the main reason for the disturbances in the function of the testis. It is also concluded that these particles may have a potential reproductive toxicity in adult male rats. Further studies are thus needed to determine its mechanism of action upon spermatogenesis.

Cadmium toxicity: effects on human reproduction and fertility.

Background Cadmium (Cd) is a non-essential toxic heavy metal, an environmental toxicant, and toxic at a low concentration, and it has no known beneficial role in the human body. Its exposure induces various health impairments including hostile reproductive health. Objective The present review discusses the information on exposure to Cd and human reproductive health impairments including pregnancy or its outcome with respect to environmental and occupational exposure. Methods The present review provides current information on the reproductive toxic potential of Cd in humans. The data were collected using various websites and consulting books, reports, etc. We have included recent data which were published from 2000 onward in this review. Results Cd exposure affects human male reproductive organs/system and deteriorates spermatogenesis, semen quality especially sperm motility and hormonal synthesis/release. Based on experimental and human studies, it also impairs female reproduction and reproductive hormonal balance and affects menstrual cycles. Based on the literature, it might be concluded that exposure to Cd at low doses has adverse effects on both human male and female reproduction and affects pregnancy or its outcome. Further, maternal prenatal Cd exposure might have a differential effect on male and female offspring especially affecting more female offspring. Hence, efforts must be made to prevent exposure to Cd. Conclusion Cd affects both male and female reproduction, impairs hormone synthesis/regulation and deteriorates pregnancy rate or its outcome even at lower doses.