Role of reactive oxygen species in male infertility.

In Westernized societies, average consumption of n-6 polyunsaturated fatty acids (PUFAs) far exceeds nutritional requirements. The ratio of n-6 to n-3 PUFAs is generally >10:1 whereas on a primitive human diet it was closer to 1:1. Diets fed to intensively farmed livestock have followed a similar trend. Both n-6 and n-3 PUFAs can influence reproductive processes through a variety of mechanisms. They provide the precursors for prostaglandin synthesis and can modulate the expression patterns of many key enzymes involved in both prostaglandin and steroid metabolism. They are essential components of all cell membranes. The proportions of different PUFAs in tissues of the reproductive tract reflect dietary consumption. PUFA supplements (particularly n-3 PUFAs in fish oil) are promoted for general health reasons. Fish oils may also benefit fertility in cattle and reduce the risk of preterm labor in women, but in both cases current evidence to support this is inconclusive. Gamma-linolenic acid containing oils can alter the types of prostaglandins produced by cells in vitro, but published data to support claims relating to effects on reproductive health are lacking. Spermatozoa require a high PUFA content to provide the plasma membrane with the fluidity essential at fertilization. However, this makes spermatozoa particularly vulnerable to attack by reactive oxygen species, and lifestyle factors promoting oxidative stress have clear associations with reduced fertility. Adequately powered trials that control for the ratios of different PUFAs consumed are required to determine the extent to which this aspect of our diets does influence our fertility.

https://bioone.org/journals/biology-of-reproduction/volume-77/issue-2/biolreprod.107.060558/Polyunsaturated-Fatty-Acids-in-Male-and-Female-Reproduction1/10.1095/biolreprod.107.060558.pdf

Polyunsaturated Fatty Acids in Male and Female Reproduction

Extensive research in our center at the Cleveland Clinic indicates that the seminal oxidative stress test has diagnostic and prognostic capabilities beyond those of conventional tests of sperm quality or functions. An oxidative stress test can accurately discriminate between fertile and infertile men and identify patients with a clinical diagnosis of male-factor infertility who are likely to initiate a pregnancy if they are followed over a period of time. In addition, the test can help select subgroups of patients with infertility in which oxidative stress is a significant factor, and who may benefit from antioxidant supplementation. Incorporation of such a test into routine andrology laboratory practice may be of particular importance to the future management of male infertility. In recent years, the generation of reactive oxygen species (ROS) in the male reproductive tract has become a real concern because of their potential toxic effects at high levels on sperm quality and function. ROS are highly reactive oxidizing agents belonging to the class of free radicals (Aitken, 1994). A free radical is defined as ‘‘any atom or molecule that possesses one or more unpaired electrons’’ (Warren et al, 1987). Recent reports have indicated that high levels of ROS are detected in semen samples of 25% to 40% of infertile men (de Lamirande et al, 1995; Padron et al, 1997). However, a strong body of evidence suggests that small amounts of ROS are necessary for spermatozoa to acquire fertilizing capabilities (Aitken, 1999). Spermatozoa, like all cells living in aerobic conditions, constantly face the oxygen (O2) paradox: O2 is required to support life, but its metabolites such as ROS can modify cell functions, endanger cell survival, or both (de Lamirande and Gagnon, 1995). Hence, ROS must be continuously inactivated to keep only a small

https://onlinelibrary.wiley.com/doi/pdf/10.1002/j.1939-4640.2002.tb02324.x

Oxidative stress and male infertility: from research bench to clinical practice.

Fetal umbilical artery flow velocity waveforms and placental resistance : Clinical significance

Reactive oxygen species (ROS) have beneficial or detrimental effects on sperm functions depending on the nature and the concentration of the ROS involved, as well as the moment and the location of exposure. Excessive generation of ROS in semen, mainly by neutrophils but also by abnormal spermatozoa, could be a cause for infertility. Hydrogen peroxide is the primary toxic ROS for human spermatozoa. Low concentrations of this ROS do not affect sperm viability but cause sperm immobilization mostly via depletion of intracellular ATP and the subsequent decrease in the phosphorylation of axonemal proteins. High concentrations of hydrogen peroxide induce lipid peroxidation and result in cell death. On the other hand, the superoxide anion appears to play a major role in the development of hyperactivation and capacitation. The observations that: (i) exogenously generated superoxide anions induce hyperactivation and capacitation; (ii) capacitating spermatozoa themselves produce elevated concentrations of superoxide anion over prolonged periods of time; and (iii) removal of this ROS by superoxide dismutase prevents sperm hyperactivation and capacitation induced by various biological fluids, stress the importance of the superoxide anion in these processes.

Impact of reactive oxygen species on spermatozoa: a balancing act between beneficial and detrimental effects

Increased reactive oxygen species formation in semen of patients with spinal cord injury.

Congenital absence of the vagina

Cardiovascular changes associated with fetal breathing.

Antiestrogenic Effect of Clomiphene in the Human Being

We report two female sibs, with severe split-hand/split-foot malformation associated with renal and genital anomalies. The patients also have severe mandibular hypoplasia and some other, minor anomalies. The relationship to the acro-renal "syndrome" in particular and to other phenotypes with similar malformations in general is discussed. Because of consanguinity in the parents, autosomal recessive inheritance seems likely. However, the presence of a septate uterus in the mother and a double collecting system in the only living sib could also suggest possible dominant inheritance with variable expressivity.

Bernard Leduc

Papers

Increased reactive oxygen species formation in semen of patients with spinal cord injury.

Congenital absence of the vagina

Cardiovascular changes associated with fetal breathing.

Antiestrogenic Effect of Clomiphene in the Human Being

Acro‐renal‐mandibular syndrome