Studies on the testicular toxicity of 2-bromopropane,an environmental endocrine disrupter

Aim: 2-bromopropane (2-BP) is known as an environmentalendocrine disrupter. Recently its reproductive and hematopoitic tox-icity has aroused the attention of the toxicologists. The presentstudy was designed to study its testicular toxicity in male rats.Methods; Forty male SD rats were divided into four groups of10 rats each. 2-BP was administered intraperitoneally at doses of1800 mg, 600 mg or 200 mg per kg body weight per day for 5days. The control rats were given a similar volume of the vehicle.The animals were sacrificed two days after the last dose. Results: With increasing doses, the seminiferous tubular damage wasgradually increased and the percentage of spermatogonia in the totalgerm cells gradually decreased ( P < 0. 05). The seminiferoustubular area of rats taking 1800 mg/kg was also reduced significant-ly . The body weight, testicular weight and relative testicular weightof rats taking the highest dose level were all significantly decreasedas compared with the controls. (Reprod Contracep 2001; 21; 157-60)

Study on Testicular Toxicity of 2-Bromopropane, an Environmental Endocrine Disrupter

2-Bromopropane (2-BP) is considered as a kind of environmental endocrine disrupters (EDs). Its reproductive and hematopoietic toxicity has aroused the attention of international toxicologists during the past five years.In the present study, we aimed to determine experimentally the testicular toxicity of 2-BP in male rats. Materials & Methods Forty SD male rats were divided into four groups of 10 rats each. The rats were intra-abdominally administered 2-BP once per day for 5 days continuously at the doses of 1800 mg/kg, 600 mg/kg, 200 mg/kg and normal saline, respectively. The rats were dissected one week after the first administration. Results The body weight, absolute testes weight and relative testes weight of the rats in 1 800 mg/kg dose group decreased significantly with comparison to those of the con- trol group,while the weight of accessory gonads showed no significant change. With the increase of dosage, the seminiferous tubules damage rate aggravated while the ratio of spermatogonia in total germ cells fell with P<0. 05. The seminiferous tubule area of rats in 1800 mg/kg group also reduced significantly. Under light microscopic examination, the spermatogonia of administered rats showed degeneration and chro- matin condensation. The nucleus of spermatocytes appeared hyperchromatic and py- knotic.Obvious testicular damage could be found in rats of high dose group, including large amount of spermatogonia necrosis or loss and reduced spermatocyte number. The electron microscopic findings were similar to those of the light microscopy, except that typical morphological change was found in the middle dose group: the structure of spermatogonia was destroyed, mitochondrion and endoplasmic reticulum scattered outside, nucleus disintegrated; some of the spermatocytes' membrane became nuclear, chromatin condensed and cogulation necrosis appeared; the nuclear membrane of round spermatids also showed slight damage. Conclusion The results indicated that testis was the target organ of 2-BP's reproduc- tive toxicity. The testicular toxicity of 2-BP started from damaging spermatogonia and its damage on spermatogonia was most obvious among all germ cells.

Pollution of Environmental Endocrine Disrupting Chemicals(EDCs) in Water and Its Adverse Reproductive Effect on Fish

Environmental endocrine disrupting chemicals （EDCs）, commonly found in the environment, come from industry and agriculture, including pesticides, fungicides, insecticides, herbicides, and other chemicals. Nowadays, more and more EDCs were released into the environment. EDCs go into water body via atmosphere sedi-mentation, surface runoff, soil eluviation, etc., so water body becomes the main place for existing. In order to attract scientific and public attention worldwide and to prevent EDCs pol ution, in this study we reviewed the classification of EDCs and their concentrations in natural water bodies, drinking water sources and water plants, and the reproductive toxicity of EDCs to fish were reviewed. EDCs could disturb the endocrine system and make reproductive organs and reproduction abnor-mal, resulting in fertility descending, reproduction function damage, community quan-tity decrease and even species extinction. In addition, EDCs could disrupt the homeostasis maintained by hormones, which would result in defects of neural de-velopment and abnormalities of the endocrine and reproductive systems. The exact molecular mechanisms have not been completely reported, but researches have suggested that multiple mechanisms were involved in the action of EDCs. Although there have been researches on the biohazard of EDCs, there stil exist problems of weakness in fundamental researches, difficulties in recognizing and identifying EDCs and high cost, which restraint the knowledge on them.

Endocrine Disruption Activity of 30-day Dietary Exposure to Decabromodiphenyl Ethane in Balb/C Mouse

Objective This study aimed to evaluate the hepatotoxicity, metabolic disturbance activity and endocrine disrupting activity of mice treated by Decabromodiphenyl ethane （DBDPE）. Methods In this study, Balb/C mice were treated orally by gavage with various doses of DBDPE. After 30 days of treatment, mice were sacrificed; blood, livers and thyroid glands were obtained, and hepatic microsomes were isolated. Biochemical parameters including 8 clinical chemistry parameters, blood glucose and hormone levels including insulin and thyroid hormone were assayed. The effects of DBDPE on hepatic cytochrome P450 （CYP） levels and activities and uridinediphosphate-glucuronosyltransferase （UDPGT） activities were investigated. Liver and thyroid glands were observed. Results There were no obvious signs of toxicity and no significant treatment effect on body weight, or liver-to-body weight ratios between treatment groups. The levels of ALT and AST of higher dose treatment groups were markedly increased. Blood glucose levels of treatment groups were higher than those of control group. There was also an induction in TSH, T3, and f T3. UDPGT, PROD, and EROD activities were found to have been increased significantly in the high dose group. Histopathologic liver changes were characterized by hepatocyte hypertrophy and cytoplasmic vacuolization. Our findings suggest that DBDPE can cause a certain degree of mouse liver damage and insufficiency. Conclusion DBDPE has the activity of endocrine disruptors in Bal/C mice, which may induce drug-metabolizing enzymes including CYPs and UDPGT, and interfere with thyroid hormone levels mediated by Ah R and CAR signaling pathways. Endocrine disrupting activity of DBDPE could also affect the glucose metabolism homeostasis.

Endocrine disrupting effects on Chinese rare minnow(Gobiocypris rarus) fed with field collected Limnodrilus sp.

The potential endocrine disrupting effects and other toxicity effects on aquatic biota resulted from food uptake was simulated by feeding the laboratory cultured rare minnow(Gobiocypris rarus) with field collected Limnodrilus sp. The results indicated that the food chain processes affected significantly the growth, slightly reduced gonadosomatic indices, and elevated hepatosomatic indices. There was an obvious vitellogenin(VTG) induction, which generally only occurred in mature female, in the serum of juvenile rare minnow and mature male when fed with Limnodrilus sp. In addition, the rare minnow feeding on Limnodrilus sp. had significantly high renal indices, it meant obvious renal hyperplasia. The present work suggested that Limnodrilus sp. from field water may contain toxic pollutants and could lead to endocrine disruption effects to the predators. It was concluded that endocrine disruptors may not only be assimilated through water, but also be bioconcentrated through food web. The results also suggested the importance of food selection in conducting the study of endocrine disruption effects using sensitive species.

Analysis of Environmental Endocrine Disrupting Activities in Wastewater Treatment Plant Effluents Using Recombinant Yeast Assays Incorporated with Exogenous Metabolic Activation System

Objective To measure the endocrine disrupting chemicals （EDCs） in wastewater and evaluate the EDCs removal efficiencies in the municipal wastewater treatment plants （WWTP）. Methods A battery of in vitro recombinant yeast bioassays incorporated with exogenous metabolic activation system （rat liver preparation, S9 mix） was conducted to assess the estrogen receptor （ER）, androgen receptor （AR）, progesterone receptor （PR）, and thyroid receptor （TR） ant/agonistic activities of effluents collected from Datansha WWTP. Results The indirect estrogenic, anti‐androgenic, anti‐progesteronic, and anti‐thyroidic activities were observed in the influent. The removal efficiencies of EDCs were above 74%, suggesting that the present wastewater treatment processes were good enough to remove most of these indirect endocrine disrupting chemicals. Conclusion The incorporation of exogenous metabolic capacity into the test system was valid for the study of indirect effects on ER, AR, PR, and TR.

Endocrine disrupting chemicals in mixture and obesity,diabetes and related metabolic disorders

Obesity and associated metabolic disorders represent a major societal challenge in health and quality of life with large psychological consequences in addition to physical disabilities. They are also one of the leading causes of morbidity and mortality. Although, different etiologic factors including excessive food intake and reduced physical activity have been well identified, they cannot explain the kinetics of epidemic evolution of obesity and diabetes with prevalence rates reaching pandemic proportions. Interestingly, convincing data have shown that environmental pollutants, specifically those endowed with endocrine disrupting activities, could contribute to the etiology of these multifactorial metabolic disorders. Within this review, we will recapitulate characteristics of endocrine disruption. We will demonstrate that metabolic disorders could originate from endocrine disruption with a particular focus on convincing data from the literature. Eventually, we will present how handling an original mouse model of chronic exposition to a mixture of pollutants allowed demonstrating that a mixture of pollutants each at doses beyond their active dose could induce substantial deleterious effects on several metabolic end-points. This proof-of-concept study, as well as other studies on mixtures of pollutants, stresses the needs for revisiting the current threshold model used in risk assessment which does not take into account potential effects of mixtures containing pollutants at environmental doses, e.g., the real life exposure. Certainly, more studies are necessary to better determine the nature of the chemicals to which humans are exposed and at which level, and their health impact. As well, research studies on substitute products are essential to identify harmless molecules.

Endocrine Disruption of Cadmium in Rats Using the OECD Enhanced TG 407 Test System

Objective To evaluate the endocrine disrupting effects of cadmium （Cd） using OECD enhanced TG407 test guideline. Methods Sprague-Dawley （SD） rats were randomly divided into six groups and accordingly administered with 0, 1, 2.5, 5, 10, 20 mg/kg.BW/day of Cd by gavage for 28 days. Body weight, food consumption, hematology, biochemistry, sex hormone levels, urinary β2-microglobulin, organ weights and histopathology and estrous cycle were detected. Results Cd could significantly decrease animals＇ body weight （P〈0.05）. Serum luteinizing hormone （LH） at 10-20 mg/kg.BW groups and testosterone （T） at 2.5 and 10 mg/kg.BW groups decreased significantly （P〈0.05）. However, no statistically significant change was found in urinary β2-microglobulin among Cd-treatment groups （P〉0.05）. Endpoints related to female reproduction including uterus weight and histopathological change at 10-20 mg/kg.BW groups showed significant increase （P〈0.05）. While among male rats in 2.5, 10, 20 mg/kg.BW groups, weight of prostate, thyroids, and seminal vesicle glands significantly decreased （P〈0.05）. Moreover, no histopathological change was observed in kidney. Conclusion Results suggested that Cd can cause endocrine disrupting effects in SD rats. Comparing with possible renal toxicity of Cd, its toxicity on endocrine system was more sensitive.

Research Development of Endocrine Disrupting Chemicals(EDCs) in Water in China

More and more importance has been attached to the problem of endocrine disrupting chemicals (EDCs) since 1960s. This article elaborates the recent research progress of EDCs in water and the trends in the near future in China.

Hypoxic and temporal variation in the endocrine disrupting toxicity of perfluorobutanesulfonate in marine medaka(Oryzias melastigma)

Perfluorobutanesulfonate(PFBS)is an emerging pollutant capable of potently disrupting the sex and thyroid endocrine systems of teleosts.However,the hypoxic and temporal variation in PFBS endocrine disrupting toxicity remain largely unknown.In the present study,adult marine medaka were exposed to environmentally realistic concentrations of PFBS(0 and 10μg/L)under normoxia or hypoxia conditions for 7 days,aiming to explore the interactive behavior between PFBS and hypoxia.In addition,PFBS singular exposure was extended till 21days under normoxia to elucidate the time-course progression in PFBS toxicity.The results showed that hypoxia inhibited the growth and caused the suspension of egg spawn regardless of PFBS exposure.With regard to the sex endocrine system,7-day PFBS exposure led to an acute stimulation of transcriptional profiles in females,which,subsequently,recovered after the 21-day exposure.The potency of hypoxia to disturb the sex hormones was much stronger than PFBS.A remarkable increase in estradiol concentration was noted in medaka blood after hypoxia exposure.Changes in sex endocrinology of coexposed fish were largely determined by hypoxia,which drove the formation of an estrogenic environment.PFBS further enhanced the endocrine disrupting effects of hypoxia.However,the hepatic synthesis of vitellogenin and choriogenin,two commonly used sensitive biomarkers of estrogenic activity,failed to initiate in response to the estrogen stimulus.Compared to sex endocrine system,disturbances in thyroidal axis by PFBS or hypoxia were relatively mild.Overall,the present findings will advance our toxicological understanding about PFBS pollutant under the interference of hypoxia.

Food contaminants and potential risk of diabetes development:A narrative review

The number of people diagnosed with diabetes continues to increase,especially among younger populations.Apart from genetic predisposition and lifestyle,there is increasing scientific and public concern that environmental agents may also contribute to diabetes.Food contamination by chemical substances that originate from packaging materials,or are the result of chemical reactions during food processing,is generally recognized as a worldwide problem with potential health hazards.Phthalates,bisphenol A(BPA)and acrylamide(AA)have been the focus of attention in recent years,due to the numerous adverse health effects associated with their exposure.This paper summarizes the available data about the association between phthalates,BPA and AA exposure and diabetes.Although their mechanism of action has not been fully clarified,in vitro,in vivo and epidemiological studies have made significant progress toward identifying the potential roles of phthalates,BPA and AA in diabetes development and progression.These chemicals interfere with multiple signaling pathways involved in glucose and lipid homeostasis and can aggravate the symptoms of diabetes.Especially concerning are the effects of exposure during early stages and the gestational period.Well-designed prospective studies are needed in order to better establish prevention strategies against the harmful effects of these food contaminants.

Occurrences of Glucocorticoids in Aquatic Environment and Their Removal during Wastewater Treatment

Glucocorticoids(GCs) are a group of endocrine-disrupting compounds(EDCs) frequently prescribed against various medical conditions.Recently,GCs have been shown to be effective in managing septic shock in patients infected with the 2019 novel coronavirus(COVID-19).Due to colossal consumption and potential risks to aquatic organisms,GCs have immensely attracted the focus of the scientific research community as a water pollutant.Therefore,the aim of this paper is to review the current knowledge on the occurrence of various GCs in the aquatic environment and their removal during wastewater treatment.A variety of GCs are ubiquitous in surface water,hospital wastewater,and sewage water worldwide.And the minimum concentration in volume is below 0.01 ng/L,and the maximum one is 10 000 ng/L,and enter the environment through hospital and urban wastewater discharging.Compared with natural GCs,higher risks to aquatic environments could be induced by synthetic GCs.The current activated sludge processes used in wastewater treatment plants(WWTPs) are not fully effective in eliminating GCs,some of which may further increase the risk of GC in the environment.In comparison with the aerobic process in WWTPs,the anaerobic and anoxic processes were found to be more efficient for GC degradation.Of the studied GCs,fluticasone propionate,clobetasol propionate,fluocinolone acetonide,and triamcinolone acetonide need more attention due to their low removal efficiencies and strong toxicity.Among the advanced treatment processes,reverse osmosis,ultraviolet irradiation,CaO_(2),and plasma could achieve significant GC activity removal while micro/ultra-filtration,chlorination,and ozonation were less efficient.

Health Impacts and Mechanisms of Per- and Polyfluoroalkyl Substances (PFAS) from Epidemiological to Toxicological

This research provides a comprehensive analysis of the health impacts of Per- and Polyfluoroalkyl Substances (PFAS) through an integration of epidemiological and toxicological studies. The study identifies significant correlations between PFAS exposure and adverse health outcomes, including thyroid dysfunction, elevated cholesterol levels, and increased risk of specific cancers. Utilizing a mixed-methods approach, the research combines a systematic review and meta-analysis of recent literature with in vitro and in vivo toxicological experiments. The epidemiological analysis reveals increased risks of thyroid dysfunction, cholesterol elevation, and certain cancers among PFAS-exposed individuals. Toxicological findings further corroborate these results, showing dose-dependent cytotoxic effects in human cell lines and endocrine disruption in rodent models. The study emphasizes the importance of regulatory measures to mitigate PFAS exposure and the urgent need for more comprehensive research into their long-term effects. The integration of epidemiological and toxicological data underscores the significant health risks posed by PFAS, highlighting the necessity of immediate action to limit exposure and develop safer alternatives.

Removal of endocrine disrupting chemicals from water through urethane functionalization of microfiltration membranes via electron beam irradiation

Polyethersulphone(PES)membranes modified with urethane functional groups were prepared through an interfacial reaction using electron beam irradiation.The removal of eight endocrine disrupting chemicals(EDCs)was studied using both pristine and functionalized PES membranes.The prepared membranes underwent characterization using several techniques,including attenuated total reflectance-Fourier transform infrared(ATR-FTIR)spectroscopy,scanning electron microscopy,contact angle analysis,and measurements of pure water flux.Furthermore,dynamic adsorption experiments were conducted to evaluate the adsorption mechanism of the prepared membrane toward the eight EDCs.The urethane functionalized membranes were hydrophilic(52°contact angle)and maintained a high permeate flux(26000 L/h m^(2) bar)throughout the filtration process.Dynamic adsorption results demonstrated that the introduction of urethane functional groups on the membranes significantly enhanced the removal efficiency of 17β-estradiol,estriol,bisphenol A,estrone,ethinylestradiol,and equilin.The adsorption loading of 17β-estradiol on the functionalized PES membrane was 6.7±0.7 mg/m^(2),exhibiting a 5-fold increase compared to the unmodified PES membrane.The membranes were successfully regenerated and reused for three adsorption cycles without experiencing any loss of adsorption capacity.

Toxic Effects of Atrazine on Reproductive System of Male Rats

Objective This study was designed to evaluate the toxic effects of Atrazine （ATZ） on the reproductive system of male rats. 〈br〉 Methods Male Sprague-Dawley rats were exposed to ATZ by gavage at dosages of 0, 38.5, 77, and 154 mg/kg bw/day for 30 d. The toxic effects of ATZ to rats were assessed through histopathologcal observation, spermatozoa quality evaluation, testicular marker enzyme indicators, antioxidant capacity and reproductive hormone levels. Results Significant adverse effects on reproductive system were observed in rats exposed to ATZ at different dosages compared with 0 mg/kg group, including an irregular and disordered arrangement of the seminiferous epithelium in 154 mg/kg group;a decreased spermatozoa number and an increased spermatozoa abnormality rate in 77 and 154 mg/kg groups;decreased levels of acid phosphatase （ACP）, alkaline phosphatase （AKP）, lactic dehydrogenase （LDH）, and succinate dehydrogenase （SDH） with the increasing of ATZ concentration; a decreased level of total antioxidant capacity （TAC） in a dose-dependent manner, and a decreased reduced glutathione （GSH） level and an increased malondialdehyde （MDA） content in 154 mg/kg group;and decreased serum levels of testosterone （T） and inhibin-B （INH-B） and an increased serum level of follicle stimulating hormone （FSH） in 77 and 154 mg/kg groups, and an increased serum level of luteinizing hormone （LH） in 154 mg/kg group. Conclusion These results suggested that relatively high doses of ATZ could exert reproductive toxicity of male rats.

Similar causes of various reproductive disorders in early life

During the past few decades, scientific evidence has been accumulated concerning the possible adverse effects of the exposure to environmental chemicals on the well-being of wildlife and human populations. One large and growing group of such compounds of anthropogenic or natural origin is referred to as endocrine-disrupting chemicals （EDCs）, due to their deleterious action on the endocrine system. This concern was first focused on the control of reproductive function particularly in males, but has later been expanded to include all possible endocrine functions. The present review describes the underlying physiology behind the cascade of developmental events that occur during sexual differentiation of males and the specific role of androgen in the masculinization process and proper organogenesis of the external male genitalia. The impact of the genetic background, environmental exposures and lifestyle factors in the etiology of hypospadias, cryptorchidism and testicular cancer are reviewed and the possible role of EDCs in the development of these reproductive disorders is discussed critically. Finally, the possible direct and programming effects of exposures in utero to widely use therapeutic compounds, environmental estrogens and other chemicals on the incidence of reproductive abnormalities and poor semen quality in humans are also highlighted.

Gene-environment interactions in male reproductive health： special reference to the aryl hydrocarbon receptor signaling pathway

Over the last few decades, there have been numerous reports of adverse effects on the reproductive health of wildlife and laboratory animals caused by exposure to endocrine disrupting chemicals （EDCs）. The increasing trends in human male reproductive disorders and the mounting evidence for causative environmental factors have therefore sparked growing interest in the health threat posed to humans by EDCs, which are substances in our food, environment and consumer items that interfere with hormone action, biosynthesis or metabolism, resulting in disrupted tissue homeostasis or reproductive function. The mechanisms of EDCs involve a wide array of actions and pathways. Examples include the estrogenic, androgenic, thyroid and retinoid pathways, in which the EDCs may act directly as agonists or antagonists, or indirectly via other nuclear receptors. Dioxins and dioxin-like EDCs exert their biological and toxicological actions through activation of the aryl hydrocarbon-receptor, which besides inducing transcription of detoxifying enzymes also regulates transcriptional activity of other nuclear receptors. There is increasing evidence that genetic predispositions may modify the susceptibility to adverse effects of toxic chemicals. In this review, potential consequences of hereditary predisposition and EDCs are discussed, with a special focus on the currently available publications on interactions between dioxin and androgen signaling.

Persistent organic pollutants and male reproductive health

Environmental contaminants such as persistent organic pollutants （POPs） are man-made bioaccumulative compounds with long half-lives that are found throughout the world as a result of heavy use in a variety of consumer products during the twentieth century. Wildlife and animal studies have long suggested adverse effects of exposure to these compounds on human reproductive health, which, according to the endocrine disrupter hypothesis, are ascribed to the compounds＇ potential to interfere with endocrine signaling, especially when exposure occurs during certain phases of fetal and childhood development. An extensive number of epidemiological studies have addressed the possible effects of exposure to POPs on male reproductive health, but the results are conflicting. Thus far, most studies have focused on investigating exposure and the different reproductive health outcomes during adulthood. Some studies have addressed the potential harmful effects of fetal exposure with respect to malformations at birth and/ or reproductive development, whereas only a few studies have been able to evaluate whether intrauterine exposure to POPs has long-term consequences for male reproductive health with measurable effects on semen quality markers and reproductive hormone levels in adulthood. Humans are not exposed to a single compound at a time, but rather, to a variety of different substances with potential divergent hormonal effects. Hence, how to best analyze epidemiological data on combined exposures remains a significant challenge. This review on POPs will focus on current knowledge regarding the potential effects of exposure to POPs during fetal and childhood life and during adulthood on male reproductive health, including a critical revision of the endocrine disruption hypothesis, a comment on pubertal development as part of reproductive development and a comment on how to account for combined exposures in epidemiological research.

Combined Subchronic Toxicity of Bisphenol A and Dibutyl Phthalate on Male Rats

Objective To evaluate the combined subchronic toxicity of bisphenol A（BPA） and dibutyl phthalate（DBP） in male Sprague Dawley（SD） rats.Methods Forty 4‐week‐old male rats weighing 115‐125 g were randomly divided into BPA‐treated,DBP‐treated group,BPA＋DBP‐treated and control groups and fed with a soy‐ and alfalfa‐free diet containing 285.4 ppm BPA,285.4 ppm DBP,285.4 ppm BPA plus 285.4 ppm DBP,and a control diet,respectively,for 90 consecutive days.At the end of the study,the animals were sacrificed by exsanguination via the carotid artery under diethyl etherane aesthesia and weighed.Organs,including liver,kidneys,spleen,thymus,heart,brain,and testis underwent pathological examination.The androgen receptor（AR）,gonadotropin‐releasing hormone receptor（GNRHR）,and progesterone hormone receptor（PR） genes from the hypothalamus were detected by real‐time PCR.The biomedical parameters were analyzed.Results No significant difference was found in food intake,body weight,tissue weight,organ/brain weight ratio,and biomedical parameters among the four groups（P〉0.05）.However,BPA and DBP up‐regulated AR,PR and GNRHR expression levels in rats and showed a synergistic or an additive effect in the BPA＋DBP group.Conclusion The combined subchronic toxicity of BPA and DBP is synergistic or additive in male SD rats.

Gene-environment interaction and male reproductive function

As genetic factors can hardly explain the changes taking place during short time spans, environmental and lifestyle-related factors have been suggested as the causes of time-related deterioration of male reproductive function. However, considering the strong heterogeneity of male fecundity between and within populations, genetic variants might be important determinants of the individual susceptibility to the adverse effects of environment or lifestyle. Although the possible mechanisms of such interplay in relation to the reproductive system are largely unknown, some recent studies have indicated that specific genotypes may confer a larger risk of male reproductive disorders following certain exposures. This paper presents a critical review of animal and human evidence on how genes may modify environmental effects on male reproductive function. Some examples have been found that support this mechanism, but the number of studies is still limited. This type of interaction studies may improve our understanding of normal physiology and help us to identify the risk factors to male reproductive malfunction. We also shortly discuss other aspects of gene-environment interaction specifically associated with the issue of reproduction, namely environmental and lifestyle factors as the cause of sperm DNA damage. It remains to be investigated to what extent such genetic changes, by natural conception or through the use of assisted reproductive techniques, are transmitted to the next generation, thereby causing increased morbidity in the offspring.