Of the nine biological trace elements, zinc, copper and selenium are important in reproduction in males and females. Zinc content is high in the adult testis, and the prostate has a higher concentration of zinc than any other organ of the body. Zinc deficiency first impairs angiotensin converting enzyme (ACE) activity, and this in turn leads to depletion of testosterone and inhibition of spermatogenesis. Defects in spermatozoa are frequently observed in the zinc-deficient rat. Zinc is thought to help to extend the functional life span of the ejaculated spermatozoa. Zinc deficiency in the female can lead to such problems as impaired synthesis/secretion-of (FSH) and (LH), abnormal ovarian development, disruption of the estrous cycle, frequent abortion, a prolonged gestation period, teratogenicity, still-births, difficulty in parturition, pre-eclampsia, toxemia and low birth weights of infants. The level of testosterone in the male has been suggested to play a role in the severity of copper deficiency. Copper-deficient female rats are protected against mortality due to copper deficiency, and the protection has been suggested to be provided by estrogens, since estrogens alter the subcellular distribution of copper in the liver and increase plasma copper levels by inducing ceruloplasmin synthesis. The selenium content of male gonads increases during pubertal maturation. Selenium is localized in the mitochondrial capsule protein (MCP) of the midpiece. Maximal incorporation in MCP occurs at steps 7 and 12 of spermatogenesis and uptake dereases by step 15. Selenium deficiency in females results in infertility, abortions and retention of the placenta. The newborns from a selenium-deficient mother suffer from muscular weakness, but the concentration of selenium during pregnancy does not have any effect on the weight of the baby or length of pregnancy. The selenium requirements of a pregnant and lactating mother are increased as a result of selenium transport to the fetus via the placenta and to the infant via breast milk.

Zinc, copper and selenium in reproduction

Male factor infertility is increasing in developed countries, and several factors linked to lifestyle have been shown to negatively affect spermatogenesis. Sertoli cells are pivotal to spermatogenesis, providing nutritional support to germ cells throughout their development. Sertoli cells display atypical features in their cellular metabolism; they can metabolize various substrates, preferentially glucose, the majority of which is converted to lactate and not oxidized via the tricarboxylic acid cycle. Why Sertoli cells preferentially export lactate for germ cells is not entirely understood. However, lactate is utilized as the main energy substrate by developing germ cells and has an antiapoptotic effect on these cells. Several biochemical mechanisms contribute to the modulation of lactate secretion by Sertoli cells. These include the transport of glucose through the plasma membrane, mediated by glucose transporters; the interconversion of pyruvate to lactate by lactate dehydrogenase; and the release of lactate mediated by monocarboxylate transporters. Several factors that modulate Sertoli cell metabolism have been identified, including sex steroid hormones, which are crucial for maintenance of energy homeostasis, influencing the metabolic balance of the whole body. In fact, energy status is essential for normal reproductive function, since the reproductive axis has the capacity to respond to metabolic cues.

Metabolic regulation is important for spermatogenesis

Recent years have brought a paradigm shift for the role of the essential trace element zinc in immunity. Although its function as a structural component of many enzymes has been known for decades, current experimental evidence points to an additional function of the concentration of free or loosely bound zinc ions as an intracellular signal. The activity of virtually all immune cells is modulated by zinc in vitro and in vivo. In this review, we discuss the interactions of zinc with major signaling pathways that regulate immune cell activity, and the implications of zinc deficiency or supplementation on zinc signaling as the molecular basis for an effect of zinc on immune cell function.

Functional Significance of Zinc-Related Signaling Pathways in Immune Cells

Objective. —To examine the relationship between vasectomy and prostate cancer. Design. —Retrospective cohort study. Setting. —Husbands of nurses in 11 large states in the United States. Participants. —In questionnaires administered in 1976 and 1978, 14607 married female participants of the Nurses' Health Study reported vasectomy as the couple's form of contraception. In 1989, we contacted these 14607 women and 14 607 age-matched participants whose husbands had not had a vasectomy prior to 1978 to ascertain their husband's disease status between 1976 and 1989. Main Outcome Measure. —Diagnosis of prostate cancer. Results. —During the study period, from 1976 through 1989, 96 new cases of prostate cancer were diagnosed in the cohort. Vasectomy was associated with an increased risk of prostate cancer (age-adjusted relative risk, 1.56; 95% confidence interval, 1.03 to 2.37;P=.04). The relative risk of prostate cancer increased overtime since vasectomy. Among men who had their vasectomy 20 or more years in the past, the relative risk of prostate cancer was 1.89 (95% confidence interval, 1.14 to 3.14;P=.005), and after excluding stage A and B cases, the relative risk was 2.06 (95% confidence interval, 0.95 to 4.43;P=.07). This elevated risk of prostate cancer among vasectomized men persisted when we adjusted for smoking, alcohol consumption, educational level, body mass index, and geographical area of residence. Conclusions. —These results support evidence from other epidemiologic studies that vasectomy increases risk of prostate cancer. A biological mechanism whereby vasectomy influences the rate of prostate cancer may be related to a diminished secretory rate of prostatic fluid following vasectomy, or, alternatively, to the postvasectomy immune response to sperm antigens, which may cross-react with tumor-associated antigens and suppress tumor immunosurveillance mechanisms. (JAMA. 1993;269:878-882)

https://jamanetwork.com/journals/jama/articlepdf/403555/jama_269_7_029.pdf

A Retrospective Cohort Study of Vasectomy and Prostate Cancer in US Men

Hormonal regulation is essential to spermatogenesis. Sertoli cells (SCs) have functions that reach far beyond the physical support of germ cells, as they are responsible for creating the adequate ionic and metabolic environment for germ cell development. Thus, much attention has been given to the metabolic functioning of SCs. During spermatogenesis, germ cells are provided with suitable metabolic substrates, in a set of events mediated by SCs. Multiple signaling cascades regulate SC function and several of these signaling pathways are hormone-dependent and cell-specific. Within the seminiferous tubules, only SCs possess receptors for some hormones rendering them major targets for the hormonal signaling that regulates spermatogenesis. Although the mechanisms by which SCs fulfill their own and germ cells metabolic needs are mostly studied in vitro, SC metabolism is unquestionably a regulation point for germ cell development and the hormonal control of these processes is required for a normal spermatogenesis.

Hormonal control of Sertoli cell metabolism regulates spermatogenesis

Zinc content of spermatozoa collected from the caput and cauda portions of the rat epididymis was determined by atomic absorption spectroscopy. The results showed about 60% reduction in the spermatozoal zinc content by the time they reach the cauda epididymis. This reduction was inhibited in rats receiving micro dose oestrogen which incuced ‘functional’ sterility. It appears that the fall in zinc content of spermatozoa during their transport in the epididymis is related to sperm maturation and that oestrogen treatment interferes with this reduction in sperm zinc content.

Zinc content of maturing spermatozoa in oestrogen treated rats.

Studies on mechanism(s) of antifertility action of gossypol in rat and hamster

Structure activity relationship of some 2,3-diaryl-2H-1-benzopyrans to their anti-implantation, estrogenic and antiestrogenic activities in rat

The activities of nine enzymes of the TCA cycle were estimated in the initial segment, caput, corpus and cauda segments of epididymis and vas deferens of adult rhesus monkey and expressed as units per mg DNA. These enzymes were also estimated in epididymal segments and vas deferens of castrated and castrated-androgen replaced monkeys as well. Results indicated higher activities of most of the enzymes in vas deferens as compared to epididymal segments. All the enzymes showed marked reduction in epididymis and vas deferens after castration, the effect being much more pronounced in the epididymis, than in the vas. Androgen replacement in castrated monkeys stimulated most of the enzymes markedly in epididymis and in the vas deferens as compared to their castrated values. The response of cauda and vas deferens to exogenous androgen treatment was however moderate, as compared to the other epididymal segments. The studies indicate that energy metabolism in the epididymis (as well as in the vas deferens) is stric...

Activities and androgenic regulation of kreb cycle enzymes in the epididymis and vas deferens of rhesus monkey.

The possible physiological role of estrogen in the regulation of energy metabolism of epididymis and vas deferens of rhesus monkey was investigated. A few selected key enzymes of glycolysis (hexokinase, phosphofructokinase and pyruvate kinase) and TCA cycle (succinate dehydrogenase and malate dehydrogenase) were measured in these two organs of (a) castrated estrogen treated, (b) castrated estrogen + dihydrotestosterone (DHT) treated animals and compared with those in castrated and castrated + DHT treated animals. Results reveal that DHT stimulated the activities of all these enzymes whereas estrogen failed to stimulate any of the enzymes in castrated animals. However, estrogen in combination with DHT caused a marked stimulation of the enzymes and the response of the epididymis and vas deferens to combination treatment was significantly more than that caused by DHT alone. The results suggest that circulating estrogen in male has a physiological role and acts synergistically with androgen in regulating acce...

Archana Srivastava

Papers

Zinc content of maturing spermatozoa in oestrogen treated rats.

Studies on mechanism(s) of antifertility action of gossypol in rat and hamster

Structure activity relationship of some 2,3-diaryl-2H-1-benzopyrans to their anti-implantation, estrogenic and antiestrogenic activities in rat

Activities and androgenic regulation of kreb cycle enzymes in the epididymis and vas deferens of rhesus monkey.

Androgen-estrogen synergy in the regulation of energy metabolism in epididymis and vas deferens of rhesus monkey.