External factors affecting fertility, and how to correct their impact

Abstract

Fertility of both men and women has been negatively influenced by external factors and life style in recent decennia. Mechanisms of hormone disruption, oxidative damage, and epigenetic DNA changes play a pivotal role in this process. In Belgium, strict regulations have been imposed to reduce the exposure to xeno-estrogens, which has resulted in a partial recovery of sperm quality. At the other hand, more couples require in vitro fertilisation (IVF) whereby ovarian stimulation may be associated with epigenetic DNA hyper-methylation of follicular cells, and increased risk of carcinogenesis among offspring. In order to reduce the health risks for the offspring it is recommended to optimize the oxidative, epigenetic and metabolic situation of both parents by means of lifestyle adaptation, and the use of appropriate food supplementation before conception and during pregnancy.

Keywords: 8-OH-2 deoxyguanosine; epigenetics; food supplement; hTERT; infertility; oxidative stress.

Figure 1

— The histogram shows the proportion of docosahexaenoic acid (DHA, or cervonic acid, on the vertical axis, in mole%, mean +/- SEM) in the phospholipid fractions of the membrane of spermatozoa of normal fertile men (controls) and of patients in whom infertility is due to idiopathic oligozoospermia, or to varicocele, or to male accessory gland infection (MAGI).

Figure 2

— The diagram shows the mechanism of transition mutagenesis occurring in oxidative DNA damage. Guanine (G) is oxidised into 8-hydroxy-2 deoxyguanosine (8-OH-2dG) by the effect of reactive oxygen species, or free radicals. During DNA replication the 8-OH-2dG will bind to Thymine (T), whereas it should normally bind to Cytosine (C). The dinucleotide Thymine- Adenine (A) will replace the dinucleotide G-C in the daughter cells, which constitutes a transition mutation.

Figure 3

— In this line and dot diagram the proportion of methylation (on the vertical axis, in %) of each one of the 5 dinucleotides of the promoter region of the human telomerase reverse transcriptase (hTERT) is represented. The level of methylation of the Cytosine-Guanine 2 (CpG2) reaches 15% in two out of eight samples (samples number 3 and 7, on the horizontal axis) of follicular fluid of patients treated by IVF with ovarian stimulation.

Figure 4

— This box and whisker plots shows the concentration of 8-OH-2dG (on the vertical axis, in fMol) in the DNA of spermatozoa of infertile men, before treatment and after 6 weeks of intake of the anti-oxidant Astaxanthine (8 mg per day).