Chronic effects of maternal tobacco-smoke exposure and/or α-lipoic acid treatment on reproductive parameters in female rat offspring

ABSTRACT

Prenatal tobacco-smoke exposure negatively affects the reproductive functions of female offspring and oxidative stress plays a major role at this point. Alpha-lipoic acid (ALA), well known as a biological antioxidant, has been used as a nutritional supplement and as a therapeutic agent in the treatment of certain complications during pregnancy. We aimed to investigate the effects of maternal tobacco-smoke exposure and/or ALA administration on puberty onset, sexual behavior, gonadotrophin levels, apoptosis-related genes, apoptotic cell numbers and oxidative stress markers in the adult female rat offspring. Sprague-Dawley rats were divided into four groups; control, tobacco smoke (TS), TS+ALA and ALA groups. Animals were exposed to TS and/or ALA for 8 weeks before pregnancy and throughout pregnancy. All treatments ended with birth and later newborn female rats were selected for each experimental group. The experiment ended at postnatal day 74–77. Maternal tobacco smoke advanced the onset of puberty in the female offspring of the TS group (p < 0.05). In all treatment groups; the mean number of anogenital investigations and lordosis quality scores showed a decline, serum luteinizing hormone levels significantly increased (p < 0.05) and several histopathological changes in ovaries were observed compared to the control group. In addition, an increase in apoptotic marker levels and apoptotic cell numbers was detected in the ovaries of all treatment groups. Decreased TAS and increased TOS levels were detected in all treatment groups compared to control. These findings suggested that maternal tobacco smoke and/or ALA administration may be leading to the impaired reproductive health of female offspring.

Abbreviations: ALA: alpha-lipoic acid; LH: luteinizing hormone; FSH: follicle-stimulating hormone; TAS: total antioxidant status; TOS: total oxidant status; Apaf1: apoptotic protease-activating factor 1; Casp3: caspase 3; Casp9: caspase 9; CF: cyst follicles; 4-HNE: 4-Hidroxynonenal; 8-OHdG: 8-hydroxydeoxyguanosine; TUNEL: terminal deoxynucleotidyl transferase-mediated deoxyuridine-biotin nick end labeling; ROS: reactive oxygen species; GnRHR: gonadotropin-releasing hormone receptor; HPG: hypothalamic–pituitary–gonadal; AMPK: AMP-activated protein kinase; ELISA: enzyme-linked immunosorbent assay; cDNA: complementary DNA; qPCR: quantitative real-time PCR; FC: follicular cysts; PF: primary follicle; SF: secondary follicle; GF: graafian follicle; CL: corpus luteum; DF: degenerated follicle; AF: atretic follicle

KEYWORDS:

• Maternal tobacco smoke exposure
• alpha-lipoic acid
• puberty onset
• sexual behavior
• rat female offspring

Disclosure statement

The authors declare that there is no conflict of interest regarding the publication of this paper.

Authors contributions

Designed the study, analyzed data, revised the paper, and approved the final version: EEG; performed the research, analyzed data, drafted the article, and approved the final version: NKT, AT, NU, AY, RFA, SC, İEO.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This study was supported by the Firat University Scientific Research Projects Management Unit, Elazig, TURKEY, [Project number T.F. 17.49.