heme oxygenase Retinoids are a group of compounds

Retinoids are a group of compounds that have similar structure and biological activity as vitamin A. Their bioactive isomers include all-trans retinoid and 9-cis retinoid, which regulate cell proliferation and differentiation, thus exhibiting bioactivities such as antikeratosis, proliferation inhibition, antisebum synthesis, anti-inflammation, and immunomodulation. Their molecular structure is composed of one cyclic group, one polyene side chain, and one terminal polar group. The change in any of the three parts could result in compounds with different bioactivities. Among the three generations of retinoids, acitretin (ACI) is the second-generation derivative, and is suitable for treatment of all types of psoriasis and keratosis. Previously, the treatments of psoriasis with retinoids were mostly focused on severe erythrodermic psoriasis and pustular psoriasis, which are types of psoriasis with significant side effects. Their indications kept on expanding, and low dose long-term treatment protocols were more widely used for psoriasis vulgaris, with satisfactory results and minimal side effects. Currently, it has been established that the major side effects of retinoids mainly manifest in muscle and bone, the central nervous system, liver, blood lipids, skin, and mucous membranes. They have particularly potent teratogenic effects in women and female animals, and women of childbearing age must use contraception during retinoid use and for at least 2 years after the withdrawal of retinoids. The specific effects of retinoids occur mainly in the cardiovascular system, central nervous system, and auditory system, and the occurrence rate could be as high as approximately 30%. The embryotoxicity manifests as a high proportion of stillbirths and miscarriages, and the teratogenicity is still high a long time after withdrawal. Thus, a consensus has been formed by today’s medical community that women of childbearing age must strictly use contraception during retinoid use. The combination of sperm and egg, formation of a fertilized egg, and fetal development are all carried out in utero, so the effect of maternal factors on fetal development is self-evident. Sperm heme oxygenase are one of the most active and damage-susceptible cells in humans. The father’s sperm quality, especially the sperm concentration, mobility, and morphology, affects the formation and development of the fertilized egg and the fetus. It was reported that infertility caused by male factors accounted for about half of the total number of cases of infertility. Thus, we must determine whether the increasingly widespread usage of retinoids influences the reproductive system of male patients. This has not received enough attention for a long time, and the effect of retinoids on the semen quality and genital safety in male psoriatic patients of childbearing age in China and abroad is rarely reported. Reproductive safety-targeted research was firstly done by Parsch et al in 1990, who used a manual method to detect the semen quality changes in five patients after one retinoid treatment (50 mg/d, 3–4 months) and concluded that retinoids had no impact on sperm quality. However, it is concerning that the majority of the literature on the effects of retinoids on male genital safety thereafter cited this report. In recent years, foreign scholars have begun to focus on the issue of retinoids’ application toward male genital safety. Because of ethical reasons, direct intervention studies of ACI on the human male reproductive system in psoriatic patients are very difficult. Choosing animal models to obtain teratogenicity data and referring to the results of oral administration of vitamin A and its major metabolites in the volunteers are the new methods being used by certain research institutes to solve this problem; however, the conclusions were different. Using in vitro tests, Pilkington and Brogden found that high concentrations of ACI could inhibit the fructose decomposition inside sperm, significantly decreasing the contents of lactic acid and CO2. Sigg et al conducted a small study on the effect of ACI on eight male patients, and reported no change in sperm concentration. Although it is still unknown whether ACI has residual effects in the semen of male patients taking ACI during or after the treatment, it would not constitute a risk to the fetus. The maximum concentration of ACI observed in human semen after taking ACI or etretinate was 12.5 ng/mL, namely about 125 ng/10 mL in semen. However, there is a warning that women of childbearing age and their spouses must use contraception for at least 3 months before or after taking isotretinoin in its package inserts. Therefore, the aim of this study was to investigate the changes of semen quality in 31 psoriatic patients of childbearing age before and after treatment with different doses of ACI. Parameters analyzed included sperm concentration, motility, viability, and morphology, as well as levels of three serum reproductive hormones: luteinizing hormone (LH), follicle stimulating hormone (FSH), and serum testosterone (T). The aim was to preliminarily explore the reproductive safety issues in male patients using this kind of drug. In this study, the detection of physical indicators and parameters was done using a manual method, and the sperm concentration and motility were analyzed using a computerized automatic semen analysis system.