Ovarian aging and infertility

Abstract

The biological state of the ovum remains the key element in normal reproduction. Age-related decrease in the number of oocytes, as well as disturbed neuroendocrine function of the ovary and lesions in the uterus, contribute to reduced fertility. Decreasing number of ovarian follicles is accompanied by reduction of their quality, including mainly abnormalities of the nucleus (dispersed chromatin, decondensation of chromosomes and abnormalities connected with the spindle apparatus). This results in failed reproduction due to abnormal gametogenesis, fertilization process, early development of the embryo and abnormal implantation. This work describes age-related biochemical mechanisms conditioning molecular changes occurring due to abnormal microenvironment of the ovary; their accumulation leads to aging and to a more rapid apoptosis of the oocyte. There are many theories explaining the causes of oocyte destruction, including abnormal vascularization, oxidative stress, imbalance of free radicals, influence of toxic compounds and genetic changes. Decreased blood perfusion in the microenvironment of a maturating ovum leads to hypoxia and thus to a chain of reactions of oxidative stress. Oxidative imbalance leads to abnormalities of cellular biomolecules. Moreover, it is suggested that glycation processes in a cell, leading to the formation of compounds called AGEs (Advanced Glycation End Products), are also responsible for aging of the cells. They contribute directly to protein damage, induce a chain of reactions of oxidative stress, and increase the inflammatory reactions. Recently, the role of mitochondria and telomeres in the aging process and loss of reproductive functions has been especially underscored. Moreover, this work stresses the prognostic value of clinically used markers evaluating the ovarian reserve. The role of Anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), estradiol, inhibin B and antral follicle count (AFC) was presented in this paper.