The clinical application value of seminal plasma biochemical tests in the diagnosis of male infertility

       The World Health Organization (WHO) refers to couples of childbearing age who have lived together for more than one year, have a normal sexual history, and do not use any contraceptive measures, but the female partner is infertile due to the male partner, as male infertility. According to the WHO survey, about 15% of couples of childbearing age are infertile, with 8% to 22% of the problems occurring in the male partner, 25% to 37% in the female partner, and 21% to 38% in both partners. Infertility has become an important global medical and sociological problem.? Li Yuan, Department of Urology, Guangdong Provincial Hospital of Traditional Chinese Medicine Currently, although routine semen analysis has become an important routine tool for clinical evaluation of male fertility, male infertility is a more complex clinical syndrome. With the depth of research, biochemical indicators in seminal plasma are receiving more and more attention. It can not only understand the main tissue sources of various components in seminal plasma, but also reflect the functions of testes, epididymis and other accessory gonads, and the influence on sperm quality, which has important clinical practical significance for the comprehensive evaluation of male fertility. This paper reviews the biochemical indicators of seminal plasma that are commonly used in the clinical diagnosis of male infertility because of the large number of secretion products of each gonad.  1. The secretory function of the testes and accessory gonads?  1.1 The secretory function of testis?       Lactate dehydrogenase isoenzyme: Lactate dehydrogenase isoenzyme C4 (LDH-C4) is only found in human and mammalian mature testes and sperm cells at all levels, is a sperm-specific isoenzyme, and its synthesis is regulated by androgen secretion, is one of the main enzymes of sperm energy, and has certain antigenic properties. The activity of LDH-C4 in seminal plasma correlates with sperm density, survival, motility and acrosome reaction, and has a damaging effect on reproduction. Recent studies have found that LDH-C4 in spermatozoa of male infertility and oligospermia is reduced compared to spermatozoa of normal fertility, and the activity of LDH-C4 in seminal plasma of infertility is greater than that of normal fertility. Therefore, the measurement of its content can be used as an objective indicator to reflect the status of spermatogenic function of the testes, to evaluate the quality of semen and the ability to fertilize, and also to reflect whether the seminal tract is open or not.       The Tf is a glycoprotein. 80% of Tf in seminal plasma is secreted and synthesized by the supporting cells, and Tf is used to transfer iron from blood to germ cells to promote their development and maturation, and its level affects sperm production. The seminal plasma Tf content of infertile patients is related to sperm density, and the seminal plasma Tf content of infertile patients with normal sperm density is related to the sperm acrosome integrity rate. Low concentrations of seminal plasma Tf can cause a decrease in sperm acrosome integrity rate, which can affect the fertilization function of sperm and lead to infertility. Therefore, seminal plasma Tf can be used as an important indicator to evaluate the function of testicular supporting cells or varicocele as well as sperm fertilization function.?  1.2 Secretory function of the accessory gonads?       The secretory function of the epididymis: ①L-carnitine: carnitine is synthesized in the liver, transported to the epididymis via the blood and constantly concentrated, mainly in the free and acetylated forms. Spermatozoa are not yet mature after being produced in the testis and have neither fertilization nor motility. As sperm move from the head to the tail of the epididymis, and the content of levocarnitine in the luminal fluid of the epididymis gradually increases, the content of carnitine in sperm also increases accordingly, providing energy for sperm through carnitine promoting fat β-oxidation, promoting sperm development and maturation, enhancing the motility and fertilization ability of sperm, but at this time, the extremely high concentration of carnitine in the tail of the epididymis puts mature sperm in a However, the extremely high concentration of carnitine in the caudal epididymis at this time puts mature sperm in a relatively quiet state by inhibiting excessive motility, which facilitates sperm enrichment and storage in the caudal epididymis. Therefore, the level of seminal plasma L-carnitine directly affects sperm motility and male fertility. The measurement of seminal plasma levocarnitine is very informative for the evaluation of epididymal function. ②Neutral α-glucosidase: There are two isomers of α-glucosidase in seminal plasma, the main one is neutral α-glucosidase which only originates from the epididymis, and the other acidic α-glucosidase which is less abundant mainly originates from the prostate. The neutral α-glucosidase secreted by the epididymis can catalyze the breakdown of carbohydrates in polysaccharides or glycoproteins into glucose, which provides energy for sperm metabolism and motility. Its activity can directly affect semen quality and is positively correlated with sperm maturation, forward motion and sperm fertilization ability. In some pathological conditions, such as epididymitis and obstruction of the vas deferens, the enzyme is reduced in seminal plasma and its activity is reduced. In reflecting epididymal dysfunction, neutral α-glucosidase is more specific and sensitive than L-carnitine. ③γ-glutamyl transpeptidase (γ-GT): seminal plasma γ-GT is more abundant in the head of epididymis. Highly active γ-GT can catalyze the hydrolysis of glutathione, and the generated γ-glutamyl can combine with the high concentration of free amino acids and peptides contained in the head of epididymis to achieve trans-sperminal membrane transport. When the epididymis is afflicted, its secretion and concentration capacity decreases, and the activity of γ-GT also decreases, which affects the transmembrane transport of free amino acids and important peptides, resulting in the impairment of sperm maturation and the decrease of sperm motility. On the other hand, when obstruction occurs at the junction or below the head of the epididymis, the activity of γ-GT can also be reduced, therefore, γ-GT can be used as one of the functional indicators of the head of the epididymis. The secretory function of the spermatophore gland: ① Fructose: the characteristic substance secreted by the spermatophore? Fructose is the main source of sperm energy, and it is directly involved in sperm energy acquisition and fertilization. The content of seminal plasma fructose is affected by the level of testosterone in the blood, and androgen deficiency can cause a decrease in fructose content. Therefore, seminal plasma fructose is not only used to judge the secretory function of the seminal vesicle gland, but also indirectly reflects the function of T secretion by the testicular interstitial cells, which is of great significance to judge male fertility. The corrected fructose concentration is mostly used clinically as a judgment of seminal vesicle gland function: A low seminal plasma fructose content in patients with obstructive azoospermia, in which the seminal plasma fructose content is almost 0 in patients with vas deficiency and seminal vesicle deficiency; B higher seminal plasma fructose concentration in patients with non-obstructive azoospermia than in those with normal fertility, which may be related to the decreased ability of sperm to utilize fructose; C seminal vesicle atrophy caused after seminal vesicle inflammation, as well as relative androgen deficiency, which can make lower seminal plasma fructose, D incomplete ejaculation or too frequent ejaculation may also lead to lower fructose content; E as an aid to the diagnosis of retrograde ejaculation, bladder urine (containing semen) is taken after ejaculation for fructose determination. Prostaglandins (PG): PG is widely distributed in various tissues and body fluids in the body, but semen contains the most types of PG and the highest concentration. 15 types of PG are known to be included in human semen, among which PGE2 and PGF2α have obvious effects on the male reproductive system. PGE2 can stimulate the increase of intracellular cAMP and increase sperm motility, while PGF2α can reduce cAMP or increase PG plays an anti-spermatogenic role by interfering with testicular vascular function, stimulating testicular varicocele-like muscle cell contraction and inhibiting testosterone production, which correlates with sperm density. PG content in seminal plasma is regulated by testosterone, and in turn PG has an effect on testosterone production. In addition, PG has a contractile function on the smooth muscle of the vas deferens, the smooth muscle of the female genital tract and the cavernous muscle of the penis, which also plays a physiological role in promoting sperm transport, facilitating the passage of sperm through the cervical mucus and enhancing penile erection and ejaculation, etc.?       The amount of zinc, citric acid and acid phosphatase (ACP) in the semen is a reliable indicator of the prostate’s secretory function, and there is a good correlation between them. ①Zinc: The prostate is one of the organs in the body that contains the most zinc. The zinc content in normal human seminal plasma is 1.2 to 3.8 mmol/L, which is 100 times higher than that in plasma, which reflects the importance of seminal plasma zinc in maintaining sperm motility function. Zinc in seminal plasma has a very important role in male reproductive function, mainly in: influencing testicular interstitial cell function; perpetuating lipid oxidation in sperm cell membranes, maintaining cell structural stability and physiological permeability, and thus maintaining good sperm motility; maintaining sperm chromatin stability; scavenging oxygen free radicals produced by leukocytes and defective sperm, reducing the toxicity of oxygen free radicals to sperm; and anti-bacterial infection, etc. Therefore, the zinc content of seminal plasma can be used as one of the indicators of prostate function. Citric acid: The citric acid content in seminal plasma is high, almost all of which originates from the prostate gland, and the content in seminal plasma ranges from 1.4 to 6.3 mmol/L. Citric acid has a strong buffering effect and plays an important role in maintaining the osmotic pressure balance and moderate pH of seminal plasma, but has no significant correlation to sperm metabolism. Citric acid production is regulated by androgens, and its level also indirectly reflects serum testosterone.
(Excerpted from Prof. Liu Jihong)