FSH binds to the FSH receptor (FSHR) of granulosa cells in the ovarian follicles. LH binds to LH receptor (LHR) of thecal cells (in case of ovarian follicles) and Leydig cells (in case of testis). Cholesterol presents the precursor molecule for all steroidogenic hormones, including sex hormones. The production and function of steroid hormones will be discussed in the next chapter. Besides, the phthalates modification of gene expression can also influence the onset of cancer. The function of some genes regulating male and female reproductive system development . Altered gene expression directly influences reproductive health and hormone secretion 238,241. Contrarily, at 13 mg/kg/day, the mixture of phthalates (DBP, BBzP, DEHP, DiNP) increased the expression of Lhr in male C57/BL6 mice . Altered hormonal balance can be influenced by the phthalates’ impact on the intracellular signaling. The PPAR, ERα, and ERβ ligand-binding domains are significantly larger, allowing for access to diverse groups of small molecules, especially environmental chemicals 158,234. In silico studies observed that HMWP had a higher affinity to SHBG in comparison with LMWP. Phthalates effect on the HPG axis and steroidogenesis (epidemiological studies). The study by Lee et al. confirmed that DEP acts like an estrogenic chemical. Results from in vitro studies confirm the existence of these inconsistencies. Mendiola et al. observed decreased estradiol levels in men with increased levels of MEHP. Some animal species and strains, seem to be less sensitive to phthalate-induced toxicity, and part of this variability may be attributed to differences in phthalate biotransformation 187,188. Contributed to the concept, and the interpretation of the data concerning the intracellular mechanisms of phthalate toxicity. The other example could be a deficit of information about cancer occurrence in phthalate-exposed men. The available publications report that phthalates can either delay or induce precocious puberty onset. A Romanian study involved 37 women diagnosed with cervical cancer aged 26–76. A US study by Adibi et al. among 283 pregnant women showed that urinary levels of ∑DEHP during pregnancy caused birth after the 41st gestational week or increased the probability of the section . This study reported significantly higher levels of ∑DBP among the women with recurrent miscarriage . Specifically, studies have argued that BAT provides a more accurate reflection of androgen status than total testosterone (55, 57). In other words, those with high exposure levels may not show the strongest associations or even associations in the same direction as those with lower concentrations of exposure. Another potential reason for the different associations by age are differences in the distribution of phthalate metabolite concentrations.
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