Male infertility is a global concern that is becoming increasingly common. Seminal work by Levine et al. found the prevalence of male infertility to be increasing, though predominantly in the Western world.
However, in an update from the same group it was found that the prevalence of male infertility had increased globally by 76.9% when compared to decades earlier.1,2 Non-obstructive azoospermia (NOA) represents the most severe form of male infertility estimated to affect 10-15% of the infertile male population.
While many postulates have been proposed to explain these troubling trends, a hypothesis rapidly gaining traction as a potential etiology is endocrine disrupting chemicals (EDCs). European and United States environmental agencies describe EDCs as chemicals that interfere with the endocrine system, mimicking or disrupting normal hormonal function and causing adverse effects on humans and wildlife, including their progeny. Although their deleterious effects on fertility and azoospermia are becoming better documented, their direct effect on male fertility is still somewhat unknown and demands greater etiologic discussion.
The different classes and estimated raw number of these environmental toxins is truly astounding. EDCs are thought to adversely affect not only the hypothalamic-pituitary axis and work as a hormone disruptor, but they are additionally thought to structurally damage testicular parenchyma, directly harm Leydig and Sertoli cells, and even alter sperm DNA and epigenetic integrity.3 In addition to causing implicit harm as aforementioned, EDCs may also cause infertility by predisposing to cancer and other health issues that either precipitate or exacerbate infertility and azoospermia. Animal, and now human studies, have found that high levels of EDCs have been linked to abnormalities of the genital apparatus – cryptorchidism and hypospadias – and the development of testicular tumors. Furthermore, maternal exposure to EDCs has also been found to have a predilection for generating testicular tumors in progeny.4
A particularly insidious form of EDC - also a modern ecological conundrum - is the ubiquitous pollution from plastic, specifically microplastics and nanoplastics. Plastics have been found on every corner of the Earth, and animal studies have shown that they accumulate in the ovaries, testes, and corporal tissues. This in turn triggers inflammatory and oxidative damage to germ cells and sperm, thus impairing spermatogenesis.5 Moreover, studies are beginning to emerge that are drawing more direct links to these chemicals as a possible cause of the population level declines as discussed, though more data is required for causation. Hence, among the many classic etiologies discussed, the effects of the environment on male fertility may begin to overtake many of the traditional etiologies learned in medical school and residency. It is therefore incumbent upon the reproductive physician to become familiar with these classic etiologies and be aware of now emerging etiologies of male infertility and azoospermia.
Written by:
- Logan Hubbard, Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI
- Amarnath Rambhatla, Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI
- Sidney Glina, Department of Urology, ABC Medical School, Av Lauro Gomes, Santo André, Brazil
References:
- Levine H, Jørgensen N, Martino-Andrade A, et al. Temporal trends in sperm count: a systematic review and meta-regression analysis of samples collected globally in the 20th and 21st centuries. Hum Reprod Update. Mar 01 2023;29(2):157-176. doi:10.1093/humupd/dmac035
- Levine H, Jørgensen N, Martino-Andrade A, et al. Temporal trends in sperm count: a systematic review and meta-regression analysis. Hum Reprod Update. Nov 01 2017;23(6):646-659. doi:10.1093/humupd/dmx022
- Lahimer M, Abou Diwan M, Montjean D, et al. Endocrine disrupting chemicals and male fertility: from physiological to molecular effects. Front Public Health. 2023;11:1232646. doi:10.3389/fpubh.2023.1232646
- Cannarella R, Gül M, Rambhatla A, Agarwal A. Temporal decline of sperm concentration: role of endocrine disruptors. Endocrine. Jan 2023;79(1):1-16. doi:10.1007/s12020-022-03136-2
- Marcelino RC, Cardoso RM, Domingues ELBC, Gonçalves RV, Lima GDA, Novaes RD. The emerging risk of microplastics and nanoplastics on the microstructure and function of reproductive organs in mammals: A systematic review of preclinical evidence. Life Sci. Apr 15 2022;295:120404. doi:10.1016/j.lfs.2022.120404