Abstract
The medical comorbidities including skin diseases are associated with male infertility. The most common cause of male infertility is the inability of testes to produce sperm; however, the influence of persistent dermatitis on testicular function has not been elucidated so far. We investigated the relationship between skin inflammation and impaired sperm production using a spontaneous dermatitis mouse model. We examined the breeding records of dermatitis mice and their wild-type littermates. Sperm count, motility, and viability were analyzed by direct microscopic observation and flow cytometry. In addition, testis and epididymis were histologically examined. Finally, sperm viability was evaluated in another dermatitis mouse model and in wild-type mice in which inflammatory cytokines were intraperitoneally administered. Compared to wild-type littermate mice, the number of children born was lower in mice with dermatitis. The body weight and testis size were decreased age-dependently. In the skin disease group, the sperm count and movement ratio were clearly decreased, and reduced sperm viability was observed. Histological examination revealed the detachment of Sertoli cells and reduced spermatogenesis. The fibrosis of epididymal stroma was severe, and it might affect defective sperm maturation in the epididymis. In addition, this phenomena was reproduced by a hapten applied dermatitis mouse model and the intraperitoneal administration of inflammatory cytokines. Once the skin is inflamed, inflammatory cytokines are produced and released, which may affect testicular and sperm function. Additional studies are needed to determine the relationship between male infertility and severe dermatitis in human.
Highlights
Infertility is a disease of the reproductive system defined by the failure to achieve a clinical pregnancy for 12 months or more with regular unprotected sexual intercourse [1], and it is becomingBiomedicines 2020, 8, 293; doi:10.3390/biomedicines8090293 www.mdpi.com/journal/biomedicinesBiomedicines 2020, 8, 293 a widespread concern
We previously reported that inflamed skin produces and releases large amounts of pro-inflammatory cytokines including interleukin (IL)-1α/β compared to normal skin, which inflow into the systemic circulation, affecting distant organs
Our results showed that severe dermatitis leads to multiple alterations of spermatogenesis and sperm viability
Summary
Infertility is a disease of the reproductive system defined by the failure to achieve a clinical pregnancy for 12 months or more with regular unprotected sexual intercourse [1], and it is becomingBiomedicines 2020, 8, 293; doi:10.3390/biomedicines8090293 www.mdpi.com/journal/biomedicinesBiomedicines 2020, 8, 293 a widespread concern. Increasing evidence has shown that male infertility is associated with an increased risk of common and incident tumors and cardiovascular, metabolic, and autoimmune diseases [4]. These processes may include genetic, developmental, or lifestyle-based factors; the exact nature of these associations remains unknown. The most common cause of male infertility is the inability to produce sperm in the testes, which occurs in approximately two-thirds of infertile men [4,5,6], and various studies have been conducted for sperm dysfunction [7,8], including the malformation of sperm heads [9,10], ciliopathy [8], and thyroid dysfunction [11], but the details of sperm dysfunction have not been determined. Focusing on skin diseases can be divided into congenital and acquired
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