Protective Mechanism of Luteinizing Hormone and Follicle-Stimulating Hormone Against Nicotine-Induced Damage of Mouse Early Folliculogenesis.

Wen-Xiang Liu,Wei Shen,Shun-Feng Cheng,Shao-Jing Tan,Yan-Jie Zhang,Francesca Gioia Klinger,Donatella Farini,Massimo De Felici,Yu-Feng Wang

doi:10.3389/fcell.2021.723388

Abstract

Previous studies have shown that nicotine could impair the germ cell cyst breakdown and the primordial follicle assembly by autophagy. In this paper, we discovered that luteinizing hormone (LH) and follicle-stimulating hormone (FSH) could counteract the damage caused by nicotine of mouse germ cell cyst breakdown. The neonatal mice were separately intraperitoneally injected with nicotine, nicotine plus LH, nicotine plus FSH, and saline (control) for 4 days. Compared with the nicotine group, the quality of oocytes and the number of follicles were remarkably increased in the nicotine plus LH group or nicotine plus FSH group. LH and FSH could alleviate nicotine-induced oocyte autophagy by different pathways. LH reduced the nicotine-induced autophagy by restoring the phosphorylation level of adenosine 5′-monophosphate-activated protein kinase α-1, while FSH by downregulating the phosphorylation level of Forkhead box class O 1. In addition, in a subsequent study of 6-week mice in different treated groups, we found that LH and FSH supplementation significantly improved normal maturation rates, fertilization rates, and embryo’s developmental potential of oocytes in oocytes exposed to nicotine. Taken together, these results suggested that LH and FSH could counteract the damage caused by nicotine and finally ensure normal germ cell cyst breakdown and early embryo development.

Highlights

Smoking has long been a well-established risk factor in human reproductive conditions, especially in women who smoke during pregnancy, which is associated with various pregnancy complications (Kharrazi et al, 2004)
The statistical results showed that 100 mIU/kg luteinizing hormone (LH) or 100 mIU/kg follicle-stimulating hormone (FSH) were the lowest concentrations for inhibiting the effect of nicotine on the cyst breakdown of the ovary without changing the total oocyte number (Figure 1, Supplementary Figure 1, and Supplementary Table 3)
We found that nicotine was able to significantly increase the phosphorylation level of adenosine 5 -monophosphate (AMP)activated protein kinase α-1 (AMPKα1), an upstream signaling of AKT and mTOR, and this increase was drastically reduced in the ovaries co-treated with LH but not in those co-treated with FSH (Figures 4C,D)

Summary

Introduction

Smoking has long been a well-established risk factor in human reproductive conditions, especially in women who smoke during pregnancy, which is associated with various pregnancy complications (Kharrazi et al, 2004). Despite a gradual decline in the number of smokers over the past few decades, there was about 10–30% of women still smoking during pregnancy in western countries (Reitan and Callinan, 2017). Nicotine inhaled by a pregnant woman after smoking can cross the LH/FSH Against Nicotine-Induced Damage placenta, exposing the fetus to nicotine (Slotkin, 1998). Luck et al (1985) proved that smoking mothers have higher levels of nicotine in their amniotic fluid, and the developing fetuses were exposed to high levels of nicotine. Evidences indicated that birth malformations and intellectual impairment in later life are linked to smoking during pregnancy, with established causality (Little et al, 2004).

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Conclusion