Fertility Impairment after Trekking at High Altitude: A Proof of Mechanisms on Redox and Metabolic Seminal Changes

Abstract

Many authors described negative but reversible effects of high-altitude hypoxic exposure on animal and human fertility in terms of sperm concentration, function, and biochemical alterations. The aim of this study was to evaluate the acute and chronic effects of high-altitude exposure on classical sperm parameters, redox status, and membrane composition in a group of travellers. Five healthy Italian males, all lowlanders not accustomed to the altitude, were evaluated after 19 days-trekking through low, moderate, and high altitudes in the Himalayas. Sperm samples were collected before (Pre), 10 days after (Post), and 70 days after the end of the expedition (Follow-up). Sperm concentration, cholesterol and oxysterol membrane content, and redox status were measured. Hypoxic trek led to a significant reduction in sperm concentration (p < 0.001, η2p = 0.91), with a reduction from Pre to Post (71.33 ± 38.81 to 60.65 ± 34.63 × 106/mL) and a further reduction at Follow-up (to 37.13 ± 39.17 × 106/mL). The seminal volume was significantly affected by the hypoxic trek (p = 0.001, η2p = 0.75) with a significant reduction from Pre to Post (2.86 ± 0.75 to 1.68 ± 0.49 mL) and with partial recovery at Follow-up (to 2.46 ± 0.45 mL). Moreover, subjects had an increase in ROS production (+86%), and a decrease in antioxidant capacity (−37%) in the Post period with partial recovery at Follow-up. These results integrated the hormonal response on thyroid function, hypothalamus−pituitary−gonadal axis, and the prolactin/cortisol pathways previously reported. An uncontrolled ROS production, rather than a compromised antioxidant activity, was likely the cause of impaired sperm quality. The reduction in fertility status observed in this study may lie in an evolutionary Darwinian explanation, i.e., limiting reproduction due to the “adaptive disadvantage” offered by the combined stressors of high-altitude hypoxia and daily physical exercise.

Keywords: altitude hypoxia; male infertility; oxidative stress; redox biology; sperm parameters; sperm physiology.

Figure 1

Sperm count results; one participant was removed from the analysis due to too low values; changes over time were significant at * p < 0.05; *** p < 0.001.

Figure 2

Cholesterol and oxysterol results.

Figure 3

EPR results of (A) ROS production rate and (B) TAC via EPR detection. ORAC results of (C) anti-peroxyl (ROO•), (D) anti-hydroxyl (•HO), and (E) anti-peroxynitrite (ONOO•) antioxidant activity of human seminal fluid. Significantly different data are displayed between brackets. Changes over time were significant at * p < 0.05; ** p < 0.01.

Figure 4

Multipanel plots of ROS production rate levels relative to (A) TAC, (B) ROO•, (C) OH•, and (D) ONOO•. The linear regression fit (solid line) is also shown and so is the correlation coefficient (r) reported in each panel. A significant linear relationship was estimated as ** p < 0.01; **** p < 0.001.

Figure 5

Study design of “Kanchenjunga Exploration and Physiology” project.

Figure 6

Scheme of the influence of high altitude on sperm count cells, cholesterol, oxysterols, reactive oxygen species (ROS) production, and antioxidant capacity. Evaluation was performed with seminal fluid collection.