Looking Inside the World of Granulosa Cells: The Noxious Effects of Cigarette Smoke

Abstract

The detrimental implications of tobacco smoke on systemic health have been widely established during the past few decades. Nonetheless, increasing evidence has begun to shed more light on the serious impact that smoke exposure could also have on mammal reproductive health in terms of overall ovarian dysfunction and gestation. A variety of these complications seem to be causally related to specific chemical substances contained in cigarette smoke and their possible effects on ovarian tissues and cells, such as granulosa cells. Granulosa cells represent the functional unit of the ovary and are able to establish a bidirectional cross-talk relationship with the oocyte during folliculogenesis, which makes them vital for its correct growth and development. Based on these premises, the current review focuses on the presence of related smoke-induced damages in granulosa cells. Data have been grouped according to the studied tobacco constituents and the molecular pathways involved, in order to synthesize their impact on granulosa cells and fertility. Attention is further brought to the correlation between electronic cigarettes and female reproduction, although there have been no investigations so far regarding e-cigarette-related granulosa cell exposure. We summarize how tobacco constituents are able to cause alterations in the “life” of granulosa cells, ranging from luteal steroidogenesis and follicular loss to granulosa cell apoptosis and activation of the autophagic machinery. Further studies have been conducted to elucidate the relationship between lifestyle and fertility as to reduce the morbidity connected with infertility.

Genetically Predicted Cigarette Smoking in Relation to Risk of Polycystic Ovary Syndrome

“… 30 Secondly, the positive correlation between smoking and androgen metabolism was reported. 31 For example, some chemical substances contained in cigarette smoke could cause changes in luteal steroidogenesis, affecting progesterone and estradiol production, as well as suppression of the oocyte-cumulus complex expansion. 32 Another influence of smoking could be its effect on insulin.…”

Impact of Cigarette Smoking on the Expression of Oxidative Stress-Related Genes in Cumulus Cells Retrieved from Healthy Women Undergoing IVF

“…The exposure to tobacco smoke constituents is known to potentially harm human reproductive health, with particular reference to the ovary. Several experimental studies conducted in vitro or in vivo showed that nicotine (with its principal metabolite-cotinine), together with benzo[a]pirene (BaP), dimethylbenz[a]anthracene (DMBA) and cadmium, exert central roles in the process of ovotoxicity, influencing the steroidogenesis, the correct follicle development and the correct meiotic progression of the oocytes [ 2 , 4 , 5 ]. Although a number of studies have explored the mechanisms behind cigarette smoke-induced ovarian toxicity, the understanding of this process remains, so far, not completely elucidated.…”

“…Among the 4000 chemicals that constitute cigarette smoke (CS), the polycyclic aromatic hydrocarbons (PAHs), nitrosamines, heavy metals, alkaloids and aromatic amines represent the most studied classes of toxicants [ 2 ]. The male and female reproductive systems represent sensitive targets of the harmful effects of cigarette smoke [ 3 , 4 , 5 ]. In women, cigarette smoke exposure is associated with earlier menopause and delayed conception [ 6 ].…”

“…In addition, cigarette smoking is linked to lower clinical pregnancy and live birth rates, together with increased spontaneous miscarriage rate [ 7 , 8 , 9 , 10 , 11 ], both in couples naturally conceiving and in those undergoing in vitro fertilization (IVF) techniques [ 6 , 7 ] compared to non-smoking couples. The ovaries are highly vulnerable to the deranging effects of cigarette smoking; steroidogenesis and folliculogenesis are the ovarian processes most affected by this exposure [ 4 , 5 ]. In addition, the cigarette smoke-induced oxidative stress (OS) appears to be one of the main causes of ovarian injury [ 12 , 13 , 14 ], together with the abnormal crosstalk between oocyte and granulosa-cells, DNA damage and increased cell death [ 2 , 4 , 5 , 15 ].…”

“…The ovaries are highly vulnerable to the deranging effects of cigarette smoking; steroidogenesis and folliculogenesis are the ovarian processes most affected by this exposure [ 4 , 5 ]. In addition, the cigarette smoke-induced oxidative stress (OS) appears to be one of the main causes of ovarian injury [ 12 , 13 , 14 ], together with the abnormal crosstalk between oocyte and granulosa-cells, DNA damage and increased cell death [ 2 , 4 , 5 , 15 ]. The OS is defined as the dysregulation between the endogenous antioxidant defense mechanisms and the production of reactive oxygen species (ROS), with a consequent excess of ROS [ 12 ].…”