Exposure to Mono-n-Butyl Phthalate in Women with Endometriosis and Its Association with the Biological Effects on Human Granulosa Cells

Abstract

To study the association between urinary phthalate metabolite levels, endometriosis, and their effects on human granulosa cells, we recruited patients who underwent laparoscopy to confirm endometriosis (n = 123) and control patients (n = 78). Liquid chromatography–tandem mass spectrometry was used to measure the following five urinary phthalate metabolites: mono-n-butyl phthalate (MnBP), mono(2-ethylhexyl) phthalate, monobenzyl phthalate, mono(2-ethyl-5-oxo-hexyl) phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate. Urinary MnBP levels were higher in patients with endometriosis than in controls after multivariable logistic regression including the number of deliveries, body mass index, and use of medicine as covariables. MnBP correlates with other phthalate metabolites. Previous studies found that endometriosis was a detrimental condition for granulosa cells. In our study, we observed whether MnBP affected granulosa cells. MnBP treatment altered the gene expression of BIRC5, BUB1B, CDC20, cyclin B1, IL-1β, TNF-α, inhibin-B, StAR, and P450ssc and attenuated the ratio of the mitochondrial membrane potential in human granulosa cells. Moreover, MnBP decreased the expression of the anti-Mullerian hormone. These findings suggest that MnBP concentration is associated with endometriosis and may affect the health and steroidogenesis of human granulosa cells.

Integration of genome-wide association study and expression quantitative trait locus mapping for identification of endometriosis-associated genes

“…In our study, the eQTL was performed on the total of 78 tissue samples for endometriosis patients with recorded SNP genotypes. The expression of inturned planar cell polarity protein ( INTU ) was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and been described in detail elsewhere 31 . Glyceraldehyde-3-phosphate dehydrogenase ( GAPDH ) mRNA was amplified using q-PCR with the forward primer 5′-gagtccactggcgtcttcac-3′ and reverse primer 5′-gttcacacccatgacgaaca-3′.…”

The Association of Bisphenol A and Phthalates with Risk of Breast Cancer: A Meta-Analysis

“…Some other epidemiologic studies have focused on the higher BPA level in women with polycystic ovarian syndrome (PCOS) [ 24 , 25 ] and the consistent conclusion can be also found in adolescents [ 26 ]. In addition, various cell cultures [ 27 ], animal models [ 28 ], and human epidemiologic data have supplied evidences that phthalates may change the endometrial environment or are possibly associated with endometriosis [ 29 ]. One recent study has described that BPA exposure may affect the expression of key severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection mediators such as angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), and furin in human tissues.…”

Human Erythrocytes Exposed to Phthalates and Their Metabolites Alter Antioxidant Enzyme Activity and Hemoglobin Oxidation

“…Many epidemiological studies have shown that phthalates, after entering the body, cause disorders of the endocrine system. They can also contribute to the development of allergies, asthma, obesity, metabolic syndrome, type 2 diabetes, cardiovascular diseases, and malignant neoplasms, and all these disorders are associated with oxidative stress induction [ 24 , 25 , 26 , 27 ].…”