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Definition: 

Infertility, a couple’s inability to conceive after one year of unprotected regular intercourse, is an important issue in the world. The use of natural products in the treatment of infertility has been considered as a possible alternative to conventional therapies. The present study aimed to investigate the effects and the mechanisms of various natural products on infertility.

1. Infertility

Female infertility can be caused by failures at various steps, including ovulation, fertilization, embryo development, embryo transport, and implantation [12]. The different responses of environment toxicity include reduced fertility, spontaneous abortions, low birth weight, impaired folliculogenesis, and even damage to the ovaries [13]. OS induces infertility in woman through a variety of mechanisms [3], having a direct effect on the oocyte, embryo, and implantation by causing cell membrane lipid peroxidation, cellular protein oxidation, and DNA damage [14]. Excess ROS in the follicle may overwhelm follicular fluid antioxidant defense and hinder the endometrium which normally functions to support the embryo and its development [3]. Appropriate development of embryo and receptive endometrium are crucial factors for successful implantation [15]. Endometrial receptivity is critical for blastocyst adhesion and invasion during the complex process of implantation. Leukemia inhibitory factor (LIF) in particular is one of the major factors that regulates endometrial receptivity. Defects of LIF expression is involved in multiple implantation failures in patients with female infertility. OS is also associated with conditions such as endometriosis, hydrosalpinges, polycystic ovary syndrome (PCOS), and unexplained subfertility [14]. In addition, there is a lack of specific genetic markers because of the absence of an inherited syndrome that could implicate a gene in the pathogenesis of female infertility [16]. Mutations in the human LH P-subunit gene recently have been reported and linked with infertility. Endometriosis is noted in up to 30–40% of infertile women. Luteinizing hormone (LH) and its receptors have been linked with endometriosis-associated infertility. Reproduction is tightly controlled by hypothalamic–pituitary–gonadal axis [17]. Reproduction systems respond to hormonal signals from the pituitary gland which, in turn, is controlled by hormones produced in the hypothalamus [18]. Interruption of these processes, in any of the functional events in either sex, leads to fertility impairment [17] including gonadal dysgenesis, amenorrhea, premature ovarian failure [18]. Mammalian reproductive physiology is primarily regulated by the gonadotrophins luteinizing hormone (LH) and follicle stimulating hormone (FSH) secreted from the anterior pituitary which act on the gonads to produce sex steroids [19]. These pituitary hormones in turn enhance the proliferation of the follicular cells and the production of estrogens (principally estradiol) by ovarian cholesterol catabolism [20]. Additionally, they can lead to and restore spermatogenesis [21]. The initiation and maintenance of mammalian infertility are connected with G-protein coupled receptor 54 (GPR54) [22]. The mutation in GPR 54 is characterized by the absence of sexual maturation and low levels of gonadotropin releasing hormones (GnRH). Abnormal GnRH secretion induces anovulation, luteal insufficiency, and premature oocyte maturation, leading to menstrual disorders, polycystic ovary syndrome (PCOS), recurrent miscarriage, and infertility [16]. Additionally, it could affect the testicular function with decrease in T release [23]. Estrogen affects granulosa cells by promotion of proliferation, suppression of apoptosis, and augmentation of FSH effects. Homeostatic maintenance of prolactine (PRL) is essential since this hormone performs multiple physiological functions [24]. Increased PRL levels can cause infertility and bone loss in both women and men. It has been reported that E2 increases serum and pituitary PRL in ovariectomized rats. In addition, precursor of E2 and P4, pregnelone sulfate also increases prolactin production in the rat pituitary. On the other hand, compounds derived from natural food and herbal medicine showing promising antioxidant and antiapoptotic potentials have been considered an alternative therapy for disease [25].

The antioxidant system plays an importance role in protecting reproductive and other biological tissues below a critical threshold of ROS, preventing negative effects on reproduction [26]. Herbal medicines possessing antioxidants reduced ROS levels, protecting germ cells from OS-mediated apoptosis [27]. They could be used as complementary, alternative medicines to promote pregnancy [28].

This entry is adapted from the peer-reviewed paper 10.3390/antiox9100957