Nanoparticles and Spermatogenesis: How do Nanoparticles Affect Spermatogenesis and Penetrate the Blood–testis Barrier

Zhou Lan; Wan-Xi Yang


Nanomedicine. 2012;7(4):579-596. 

In This Article

Abstract and Introduction


Due to the widespread use of nanomaterials in medical, industrial and military applications, the question as to whether nanoparticles (NPs) cause harmful disturbances in human health, especially on the reproductive system, remains a matter of concern. In this review, we focus mainly on the in vivo and in vitro effects of NPs on spermatogenesis at the clinical, cellular and molecular levels. In general, most NPs display adverse effects on spermatogenesis at these various levels; but, some NPs show no adverse effects. However, the mechanism underlying NP disruption of spermatogenesis and penetration of the blood–testis barrier remains unclear. In this review, we raise many hypotheses for experimental testing in order to elucidate the mechanism.


Nanotechnology is a rapidly emerging industrial area that studies and develops materials with surface structure and chemical properties on the nanoscale dimension and with special properties arising from this. One of the definitions of the term nanoscale is particles that are <100 nm in at least one dimension[1] and which are therefore called nanoparticles (NPs). However, some particles that are >100 nm but <1000 nm are also called NPs if the particles demonstrate some special properties. For example, recent advances in nanotechnology allowed the production of a unique copper nanostructure that combines two special properties of strength and ductility that are often mutually exclusive.[2]

In the past decade, the nanotechnology industry has grown rapidly worldwide and predictions indicate continued growth in the future. The cause of this rapid growth involves the ever-expanding applications of nanomaterials/NPs in the following areas: catalysts, fuel lubricants, paints, conductive inks, cosmetics, drug delivery, hydrogen storage, sensor devices, structural materials, medical therapeutics, UV light absorption, and free-radical scavengers.[3] Recently, the applications of NPs have expanded to include measurement science,[4] dermatology,[5] cancer therapy[6] and even cosmetics.[7] This rapid growth calls into question not only the health of workers at the manufacturing plant but also the health of the public due to the release of nanomaterials/NPs in the environment.

Stern and McNeil reviewed NP safety issues and identified areas of agreement and disagreement with regard to NP risk, NP exposure and NP hazards.[8] They not only indicated that a paucity of NP safety studies exist but also that the NP safety studies are predominantly acute toxicology studies, not chronic studies. In addition, the current paradigm of NP safety focuses only on NP size as the determining factor in toxicity to the exclusion of other important NP properties (e.g., surface structure, surface chemistry, inorganic or organic surface coatings) that significantly change NP biocompatibility. Other studies and reviews have also addressed the issue of safety concerns and NP toxicology.[9–14]

Epidemiologists have taken an active interest in male reproductive health because young men in some regions demonstrate suboptimal sperm quality and sperm number.[15,16] The alarming fact is that both human sperm quality and sperm number have declined in recent years and the cause is unknown in the majority of cases. The possibility of public exposure must be considered. Hoover et al. indicates that the potential routes of exposure to NPs include inhalation, dermal and possibly ingestion exposures, and that a wide range of NP sizes, shapes, functionalities, concentrations, exposure frequencies and durations are involved.[17] Despite the abovementioned findings, the role that NPs play as a reproductive toxicant in spermatogenesis remains largely unknown. In this regard, Ema et al. reviewed the reproductive and developmental toxicity of NPs.[9] Ema et al. indicated that in vivo studies show that titanium dioxide (TiO2) NPs injected subcutaneously into pregnant mice result in male offspring with altered spermatogenesis and histopathological changes in the testes, and that carbon black (CB) NPs instilled within the trachea of pregnant mice result in male offspring with altered spermatogenesis.[9] In addition, Ema et al. indicated that in vitro studies show that: TiO2 and CB NPs affect Leydig cell viability; gold NPs reduce human sperm motility; and silver, aluminum and molybdenum trioxide NPs damage spermatogonia stem cells.[9] However, we admit that no obvious clinical evidence shows a direct cause–effect relationship between the problem of human sperm quality/quantity and NPs. Cormier et al. pointed out that particles will affect the human reproductive system, but what kind of particles (NPs or non-NPs) affect the human reproductive system were not pointed out.[18] The fact that the problem of human sperm quality and quantity could be caused by multiple factors makes it impossible to come to an absolute conclusion. However, the many experimental results on model animals and considerable exposure of humans to NPs make it reasonable for us to consider that NPs may be one of the factors. Bonde et al.[19] points out that less-appropriate parameters, incomplete data and insufficient statistical methods have led to the inaccurate conclusion that the quantity as well as the quality of sperm has been declining, which was made by Farrow in 1994.[16] Bonde et al. also thought that not only environmental toxicants, but also the wide range of behavioral, medical and other factors that have the potential to damage human reproduction should be taken into consideration.[19] Our conclusion is, that according to the previous result that NPs affect animal spermatogenesis and the fact that NPs exist in our environment, we can at least give a warning that NPs may be a threat to people who are largely exposed to them.

By contrast, not all NPs will necessarily demonstrate an adverse effect leading to toxicity. For example, Shi et al. reported that nanoselenium (nano-Se) diet supplementation produced positive effects on various parameters of sperm quality in male goats.[20] Thus, NPs must be investigated on a case-by-case basis without a predetermined bias as to whether a NP will have a positive or negative effect on a particular system or parameter.

In addition, spermatogenesis occurs in a very safe environment because of the blood–testis barrier (BTB).[21] NPs, theoretically speaking, cannot penetrate the BTB. However, the following studies discussed in this article show that NPs have the capacity to penetrate the BTB while non-NPs do not.

In order to summarize the extent of our knowledge at the present time, this review mainly focuses on how NPs affect spermatogenesis at the clinical, cellular and molecular levels, and how NPs penetrate the BTB.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.