Smoking and reproduction: gene damage to human gametes and embryos

Abstract

Assisted conception is a useful methodology for detecting disturbances in clinical outcome, meiotic maturation, and genetic integrity of human gametes. Germinal cells are vulnerable to genetic damage from smoking, but can repair damage during meiosis. In ejaculated spermatozoa, repair capacity declines drastically. Smoking alters the meiotic spindle of oocytes and spermatozoa, leading to chromosome errors which affect reproductive outcomes. Smoking is associated with reduced numbers of retrieved oocytes, leading to early age of menopause. Oocyte elimination occurs preferentially during meiosis I, a period sensitive to genetic damage. Smoking inhibits embryo fragmentation; inhibition may confer survival advantage to embryos genetically altered. Smoking is associated with low sperm quality, but clinical effects are not recognized. Cadmium (a heavy metal), nicotine (a toxic alkaloid), and its metabolite cotinine, are detectable in gonadal tissues and fluids in association with smoking. Cotinine incorporates into ovarian granulosa-lutein cells, compromising the developmental potential of follicles. Benzo[a]pyrene is a carcinogenic polycyclic aromatic hydrocarbon resulting from cigarette combustion. Its reactive metabolite binds covalently to DNA, forming adducts. Smoking-related adducts were detectable in ovarian granulosa-lutein cells, oocytes, spermatozoa and preimplantation embryos. Transmission of altered DNA from smoking by spermatozoa was demonstrated in preimplantation embryos and in association with increased risk of childhood cancer.

A single, mild, transient scrotal heat stress causes DNA damage, subfertility and impairs formation of blastocysts in mice

“…Studies in mice have used a variety of techniques to determine the effects of heat stress on fertility and it is notable that similar disturbances in testicular function and reduced fertility have been recorded in animals housed at 36 8C for 12 or 24 h and those subjected to a transient scrotal heat stress at 42-43 8C for 20-60 min (Lue et al 1999, 2000, Rockett et al 2001, Setchell et al 2001, Banks et al 2005, Zhang et al 2005. Our study includes novel data on the origin of DNA damage found in sperm i.e.…”

“…in fathers who smoke, can be passed on to their children and has been linked with an increased incidence of childhood cancer in their offspring (Zenzes et al 1999, Zenzes 2000. This has caused concern over the use of sperm from subfertile men in assisted reproductive technologies (IVF and ICSI).…”

“…DNA damage rates in sperm are higher in infertile individuals (Irvine et al 2000), patients subjected to cancer therapies (Charak et al 1990, Kenney et al 2001, men who smoke (Zenzes et al 1999, Zenzes 2000 and also possibly in older men (Wyrobek et al 2006). Concerns have been expressed that using sperm with damaged DNA for intracytoplasmic sperm injection (ICSI) could have a long-term effect on the health of the children born to subfertile couples (Gosden et al 2003).…”

DNA adduct kinetics in reproductive tissues of DNA repair proficient and deficient male mice after oral exposure to benzo(a)pyrene

“…If DNA damage is not removed, this might lead to the formation of mutations in the germ line, or DNA damage may persist in sperm cells until after fertilization, thus affecting the developing embryo [Zenzes, 2000]. Further studies should elucidate whether GGR/NER works efficiently to protect the inherited DNA against mutation induction.…”

Synergism between the N-acetyltransferase 2 gene and oxidant exposure increases the risk of idiopathic male infertility

“…It is well known from the literature that oxidative stress is considered to be the major pathological mechanism of tissue injury of the male reproductive tract occurring during cigarette smoking (de Jong et al, 2014;Zenzes, 2000) and excessive alcohol drinking (de Jong et al, 2014;Emanuele and Emanuele, 2001a). Allele 590A is part of the NAT2*6A haplotype, which causes the slow-acetylator phenotype due to producing proteins that are poorly expressed, unstable or possess reduced catalytic activities (Badawi et al, 1995).…”