Cigarette smoke impairs granulosa cell proliferation and oocyte growth after exposure cessation in young Swiss mice: an experimental study

Abstract

BackgroundCigarette smoke is associated with decreased female fertility, causing damage to ovarian function and disturbing follicle development. However, the effects of cigarette toxicants on ovarian function depend on duration and intensity of exposure. The aim of this study was to assess the effects of brief, intense exposure to tobacco smoke on granulosa cell number, oocyte growth, and follicle size during puberty in female Swiss mice.MethodsTen female Swiss mice aged 35 days were exposed to tobacco smoke from 3R4F reference research cigarettes. They were exposed to an automatic smoking machine 8 h/day, 7 days/week for 15 days. Ten age-matched controls were kept in a different room and exposed to ambient air. At the end of 15 days, five mice in each group were euthanized and the ovaries were analyzed for follicular morphometry and granulosa cell count. The remaining animals were kept for an additional 30 days for further analysis as an ex-smoker group and control group. Comparison between the two groups was evaluated by the Student’s t-test or a two-way ANOVA followed by Bonferroni post-test was applied for multiple comparisons.ResultsWe found that cigarette smoke impaired antral follicular growth even after exposure cessation (p < 0.001). Both smoking and ex-smoking groups exhibited similar follicle diameter. However, at the same follicular stage, the number of granulosa cells was smaller in the ex-smoking group compared to smoking animals (p < 0.001). This was associated with increased oocyte diameter in ex-smoking animals compared to smoking animals (p < 0.01).ConclusionsThe negative effects of cigarette smoking seem to last even after exposure has been interrupted. Moreover, brief exposure during puberty may induce silent oocyte disruption, which could in turn lead to decreased fecundity rates.

Environmental pollutants, a possible etiology for premature ovarian insufficiency: a narrative review of animal and human data

“…1). This has been shown for numerous substances: BPA [47], phthalates (DEHP [39, 41], DBP [38]), PAH [41, 96], cigarette smoke [65, 76, 77, 79, 82], pesticides [51–54], dioxins [100], genistein [91], PCB [104]. Secondly, a decreased pool of primordial follicles (situation 5 in Fig.…”

“…Exposure to tobacco induces a depletion in follicle stock [75–78], according to a mechanism of apoptosis and oxidative stress [75–78]. This depletion in follicle stock seems to persist, even in the case of discontinuing smoking [79]. Only one study highlighted an increase in oxidative stress associated with a decrease in bcl-2 (anti-apoptosis genes) without being able to show a real mechanism of cellular apoptosis (no difference in the proportion of TUNEL positive cells in exposed and non exposed ovarian follicles) [77].…”

The effect of heat stress on gene expression, synthesis of steroids, and apoptosis in bovine granulosa cells

“…Evidence indicates that multiple granulosa cell dysfunctions lead to disordered ovulatory and ovarian function (Tatone et al 2008). Investigations of the effects of various agents on granulosa cells show that mycotoxin deoxynivalenol induced bovine ovarian granulosa cell apoptosis (Guerrero-Netro et al 2015), and cigarette smoke impairs granulosa cell proliferation in young Swiss mice (Paixão et al 2012). Furthermore, while much is now known about the Electronic supplementary material The online version of this article (doi:10.1007/s12192-016-0673-9) contains supplementary material, which is available to authorized users.…”

Prenatal Exposures and Anti-Müllerian Hormone in Female Adolescents

“…Preconceptual paternal smoking has been associated with DNA damage in the cord blood of the offspring whereas maternal passive smoking has not, indicating that the association of paternal smoking was transmitted via the spermatozoal genome (28). In animal models, transient tobacco exposure can inhibit granulosa cell proliferation and promote apoptosis (29, 30). Whether this can be transmitted transgenerationally is at present unknown.…”