1. Introduction
The female reproductive system becomes fertile through the action of various hormones involved in the hypothalamic-pituitary-ovarian (HPO) axis [1]. The action of the gonadotropin-releasing hormone secreted by the hypothalamus stimulates the pituitary gland to promote the secretion of the luteinizing hormone (LH) and the follicle-stimulating hormone (FSH), which are types of the gonadotropin hormone (GTH) [2]. GTH acts on the ovary to increase the secretion of steroid hormones, including estradiol (E2) and progesterone (P4) [3]. Enhanced steroid hormones inhibit the activity of the hypothalamus and pituitary gland [4].
The role of hormones in reproduction is very important, and changes in the HPO axis are caused by hormones produced in vivo. The types of exogenous hormones in the environment are diverse and have several effects. In the case of chemicals used mainly in factory processes, even if the product is not directly used, it is discarded into the environment through wastewater and exposed to humans [5,6,7]. Therefore, various chemicals present in the environment have biomagnification and accumulate in top predators [8,9,10].
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Among the endocrine-disrupting chemicals (EDC), estrogenic chemicals cause direct damage to female reproductive organs [11,12]. The effects can cause disease of the reproductive organs, leading to infertility, such as polycystic ovary syndrome (PCOS) and endometriosis (EMS). PCOS is a common disease affecting 5 to 18% of women worldwide. This causes symptoms, such as an excess of androgens, anovulation, and polycystic ovaries, which lead to various complications [13,14]. EMS is also a disease in many women, in which the endometrium attaches to the extrauterine tissue and proliferates. This symptom deforms the pelvic structure and causes pain due to adhesion to a wide range of tissues [15,16].
The causes of infertility due to exposure to these chemicals include the anti-müllerian hormone (Amh) in the ovary, Spermatogenesis and oogenesis specific basic helix-loop-helix 2 (Sohlh2), Kit ligand (Kitlg), and Head box l2 (Foxl2). The changes in the expression of genes affect follicle development and cause problems with ovulation [17] or failure of endometrial proliferation due to changes in the genes of the heart. Neural crest derivatives expressed 2 (Hand2), Fk506 binding protein 4 (Fkbp4), and Homeobox a 10 (Hoxa10) in the uterus can cause implantation difficulties [18]. Problems with the synthesis and secretion of GTH and steroid hormones can cause infertility [19,20]. Increases in GTH are associated with steroidogenic acute regulatory protein (Star); Cytochrome P450 family 11 subfamily A member 1 (Cyp11a1); Hydroxy-delta-5-steroid dehydrogenase, 3 beta-and steroid delta isomerase 1 (Hsd3b1) and Cytochrome P450 family 19 subfamily A member 1 (Cyp19a1) genes increases steroid hormone production [21]. The expression of receptors that respond to the secretion of hormones increases, and the same strong activity occurs when the hormones increase [22]. These various causes can lead to problems with the reproductive system in females related to pregnancy.
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Decamethylcyclopentasiloxane (D5; CAS number. 541-02-6), a type of cyclic volatile methyl siloxane (cVMS) used in this study, has been produced commercially since the 1940s. This compound has also been used in silicone polymers, household products, and personal care products [23]. D5, used in producing various products for lubrication purposes [24], has been released into the environment through factory processes [25,26,27]. D5 bioaccumulates, and more research is needed to examine the effect.
Female pregnancy failure is also caused by a problem in the development of the embryo. After the implantation of the fertilized egg, the cardiovascular system is first formed during the development of the mammalian embryo [28]. Problems at this stage make it difficult to deliver blood to the tissue, leading to embryonic death in utero [29]. This experiment aimed to determine whether D5 is toxic at the developmental stage at the in vitro level using the embryoid body test (EBT), which confirms the cardiac differentiation capacity of embryos [30,31,32]. In this study, the effects of D5 on the reproduction process in females were examined.
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