The effect of controlled ovarian hyperstimulation on ovarian reserve via PTEN pathway.

Reproduction & Fertility Pub Date : 2022-09-12 Print Date: 2022-07-01 DOI:10.1530/RAF-21-0075
Perihan Sezginer, Cigdem Elmas, Fatma Yıldız
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Abstract

Abstract: This study was carried out to investigate whether repeated controlled ovarian hyperstimulation (COH) affects ovarian reserve. For this reason, we aimed to show possible changes in the expression of PTEN and FOXO3, which are involved in preserving the over-reserve, after applying the COH protocol methods. For this purpose, 18 young Wistar albino female rats (8 weeks old) were randomly assigned as group 1 (control), group 2, and group 3 as 6 subjects in each group. Experimental groups were treated with 10 IU/0.1 mL pregnant mare's serum gonadotropin and a COH protocol consisting of 10 IU/0.1 mL human chorionic gonadotropin injection after 48 h. This procedure was applied three and five times to group 2 and group 3, respectively. For the control groups, the same procedures were performed with 0.1 mL of 0.9% sodium chloride solution. At the end of the experiment, the ovarium tissues were placed in a 10% neutral formaldehyde solution for light microscopic examinations. In histological sections stained with hematoxylin and eosin, the number of ovarian follicles was determined using the physical dissector method. However, the expression of PTEN, FOXO3, and LH-R molecules was evaluated by immunohistochemical methods. As a result of our study, it was concluded that COH administration reduces the expression levels of PTEN and FOXO3 proteins and LH-R, which are among the essential components of the PIK3 intracellular signaling pathway and also increased the levels of hormones such as follicle-stimulating hormone, estradiol, and luteinizing hormone, which are over-reserve markers, and causes adverse effects on the histological structure, oocyte morphology, and number of ovaries.

Lay summary: Today, approximately 10-15% of couples experience fertility problems. However, assisted reproductive techniques help people with fertility problems to get pregnant. The main purpose of these techniques is to put the sperm and egg together outside the woman's body where the eggs are fertilized and then to return the fertilized eggs (embryos) to the womb. During a woman's menstrual cycle, several hormones influence the growth of the eggs. This process can be mimicked by using various medications. Medication is given to increase the number of eggs that develop. However, this method is not the same as normal ovulation. Therefore, in our study, we wanted to examine the effect that developing multiple follicles has on the number and quality of eggs remaining for the future.

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控制性卵巢过度刺激通过PTEN途径对卵巢储备的影响。
摘要:本研究旨在研究重复控制性卵巢过度刺激(COH)是否会影响卵巢储备。出于这个原因,我们旨在展示在应用COH协议方法后,PTEN和FOXO3的表达可能发生的变化,这两种表达与保留过量储备有关。为此,将18只年轻的Wistar白化雌性大鼠(8周龄)随机分为第1组(对照组)、第2组和第3组,每组6名受试者。实验组在48小时后用10 IU/0.1 mL妊娠母马血清促性腺激素和由10 IU/0.1mL人绒毛膜促性腺激素注射组成的COH方案进行治疗。该程序分别在第2组和第3组应用3次和5次。对于对照组,使用0.1 mL 0.9%氯化钠溶液进行相同的程序。实验结束时,将卵巢组织置于10%中性甲醛溶液中进行光镜检查。在苏木精和伊红染色的组织学切片中,使用物理解剖法测定卵巢卵泡的数量。然而,PTEN、FOXO3和LH-R分子的表达通过免疫组织化学方法进行评估。作为我们研究的结果,我们得出结论,COH给药降低了PTEN和FOXO3蛋白以及LH-R的表达水平,它们是PIK3细胞内信号通路的重要成分之一,还增加了促卵泡激素、雌二醇和黄体生成素等激素的水平,这些激素是过度储备的标志物,并对组织结构、卵母细胞形态和卵巢数量造成不良影响。总结:如今,约有10-15%的夫妇遇到生育问题。然而,辅助生殖技术可以帮助有生育问题的人怀孕。这些技术的主要目的是将精子和卵子放在卵子受精的女性体外,然后将受精卵(胚胎)送回子宫。在女性的月经周期中,几种激素会影响卵子的生长。这个过程可以通过使用各种药物来模仿。给药是为了增加卵子的数量。然而,这种方法与正常排卵不同。因此,在我们的研究中,我们想检验发育多个卵泡对未来剩余卵子数量和质量的影响。
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