scholarly journals Premature Ovarian Insufficiency (POI) Induced by Dynamic Intensity Modulated Radiation Therapy via P13K-AKT-FOXO3a in Rat Models

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Lianli He ◽  
Xiaoqin Long ◽  
Nixiao Yu ◽  
Yajun Li ◽  
Xiaoyun Liu ◽  
...  
Keyword(s):  
Intensity Modulated Radiation Therapy ◽  
Female Rats ◽  
Premature Ovarian Insufficiency ◽  
Follicular Atresia ◽  
Ovarian Insufficiency ◽  
Preantral Follicles ◽  
Oxidative Markers ◽  
Oxidative Damages ◽  
Radiation Group ◽  
Radiation Induced

This study is aimed to investigate the mechanisms of radiation-induced mouse models of premature ovarian insufficiency (POI). Wistar female rats were grouped into the control, 3.2 Gy, 4.0 Gy, and 4.8 Gy groups. Overall ovarian functions were assessed with the H&E staining and ELISA. Proinflammatory cytokine secretion was analyzed ELISA, and the reactive oxygen species (ROS) levels were analyzed with immunohistochemistry. Protein expressions were analyzed by Western blot analysis. The 4.0 Gy and 4.8 Gy groups had significantly lower ovarian weight coefficients than the control and 3.2 Gy groups (after only one irradiation therapy). The 3.2 Gy radiation group induced periodic disturbance and hormone change at 4 weeks after radiation. In the 4.0 Gy and 4.8 Gy groups, the preantral follicles and antral follicles were decreased, while Atresia follicles were increased. E2 was decreased, while FSH and LH secretions were increased. The ovaries in the 4.0 Gy group were not completely atrophied, and some preantral follicles remained. Ovarian atrophy and follicular Atresia were found in the 4.8 Gy group. Inflammatory and oxidative markers were upregulated. PI3K and AKT were downregulated in the 4.0 Gy and 4.8 Gy groups, while FOXO3a was upregulated. Ovarian injuries may lead to oxidative damages and inflammatory injuries, downregulate the expression of P13k and Akt, upregulate the expression of FOXO3a, and lead to follicular atresia in the ovary.

scholarly journals Prenatal ethanol exposure induces susceptibility to premature ovarian insufficiency

2019 ◽  
Vol 243 (1) ◽  
pp. 43-58 ◽  
Author(s):  
Yuan Ni ◽  
Dan Xu ◽  
Feng Lv ◽  
Yang Wan ◽  
Guanlan Fan ◽  
...  
Keyword(s):  
Ethanol Exposure ◽  
Signalling Pathway ◽  
Female Rats ◽  
Premature Ovarian Insufficiency ◽  
Prenatal Ethanol Exposure ◽  
Steroidogenic Enzymes ◽  
Ovarian Insufficiency ◽  
Adult Rats ◽  
Primordial Follicles ◽  
Expression Levels

Prenatal ethanol exposure (PEE) adversely affects the offspring reproductive system. We aimed to confirm the susceptibility to premature ovarian insufficiency (POI) in female PEE offspring and elucidate its intrauterine programming mechanism. The pregnant Wistar female rats were intragastrically administered with 4 g/kg × day of ethanol from gestational day (GD) 9 to 20. Offspring reproductive parameters were detected on GD20, postnatal week (PW) 6 and PW12. The PEE foetuses showed a decreased number of oocytes, increased ovarian cell apoptosis and upregulated expression levels of ovarian insulin-like growth factor 1 (IGF1) signalling pathway and steroidogenic enzymes. The proportion of atretic follicles in adult rats was increased, while the number of anti-Müllerian hormone-positive antral follicles was decreased. The serum oestradiol (E2) levels were decreased, but the follicle stimulation hormone levels were elevated. The ovarian Igf1 signalling pathway was transformed from activation during puberty to relative inhibition in adulthood, and the expression levels of ovarian steroidogenic enzymes were inhibited in adulthood. Furthermore, we treated the human granulosa cell line KGN with different ethanol concentrations (15, 30, 60, 120 mM) and found that the expression of IGF1 signalling pathway components, 3β-HSD and P450arom, as well as the production of E2, was increased. After IGF1 siRNA transfection, P450arom expression and E2 production were downregulated. These results suggest that PEE induces POI susceptibility in adult females, which may be caused by over-activation of the foetal ovarian Igf1 signalling pathway and steroidogenesis under PEE, resulting in accelerated early development of folliculogenesis and depletion of primordial follicles.

Menstrual cycle characteristics in women with premature ovarian insufficiency

2019 ◽  
Author(s):  
Miomira Ivovic ◽  
Ljiljana Marina ◽  
Milina Tancic-Gajic ◽  
Zorana Arizanovic ◽  
Magdalena Stankovic ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Insufficiency
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