Cell cycle, apoptosis, cell differentiation, and lipid metabolism gene expression in endometriotic tissue and exposure to parabens and benzophenones.

AIM: To describe the expression profile in endometriotic tissue of genes involved in four signaling pathways related to the development and progression of endometriosis (cell cycle, apoptosis, cell differentiation and lipid metabolism) and to explore its relationship with the women exposure to chemicals with hormonal activity released from cosmetics and personal care products (PCPs). METHODS: This cross-sectional study, encompassed within the EndEA study, comprised a subsample of 33 women with endometriosis. Expression levels of 13 genes (BMI1, CCNB1, CDK1, BAX, BCL2L1, FOXO3, SPP1, HOXA10, PDGFRA, SOX2, APOE, PLCG1 and PLCG2) in endometriotic tissue and urinary concentrations of 4 paraben (PB) and 3 benzophenone (BP) congeners were quantified. Bivariate linear and logistic regression analyses were performed to explore the associations between exposure and gene expression levels. RESULTS: A total of 8 out 13 genes (61.5 %) were expressed in >75 % of the samples. Exposure to congeners of PBs and/or BPs was associated with the overexpression of CDK1 gene (whose protein drives cells through G2 phase and mitosis), HOXA10 and PDGFRA genes (whose proteins favor pluripotent cell differentiation to endometrial cells), and APOE (whose protein regulates the transport and metabolism of cholesterol, triglycerides and phospholipids in multiple tissues) and PLCG2 genes (whose protein creates 1D-myo-inositol 1,4,5-trisphosphate and diacylglycerol, two important second messengers). CONCLUSIONS: Our findings suggest that women exposure to cosmetic and PCP-released chemicals might be associated with the promotion of cell cycle and cell differentiation as well as with lipid metabolism disruption in endometriotic tissue, three crucial signaling pathways in the development and progression of endometriosis. However, further studies should be accomplished to confirm these preliminary data.

[Association of SARS-CoV-2 infection and administration of COVID-19 vaccines with alterations in the menstrual cycle. Literature review]. / Asociación de la infección por SARS-CoV-2 y la administración de las vacunas contra la COVID-19 con alteraciones en el ciclo menstrual. Revisión de la literatura.

A number of factors can affect a woman's menstrual cycle, including diseases or drugs, such as COVID-19 disease and vaccinations. The aim of this review is to explore the studies published to date that have studied the presence of alterations that may be related to COVID-19 or vaccination against the SARS-CoV-2 virus.We conducted a review in the PubMed database, selecting 10 articles in which the menstrual cycle of adult women of childbearing age was studied, 3 of them in which the participants had been diagnosed with COVID-19 and 7 in which the participants had been vaccinated against the SARS-CoV-2 virus.Regarding COVID-19-related disturbances, 16%-47.2% of the participants presented a prolongation of their cycle, which was more frequent in those who reported more COVID-19 symptoms, and which normalised after 1-2 cycles.Regarding the alterations described after SARS-CoV-2 vaccination, 45%-78% of participants reported menstrual cycle alterations, with disparate results for the different parameters analysed, except that the alterations resolved in about 2 months.Both COVID-19 disease and vaccination appear to be associated with the occurrence of menstrual disturbances, which are limited in time and not severe. However, studies are scarce to date, and it is important to continue to develop studies that provide scientific evidence.

Cosmetic and personal care product use, urinary levels of parabens and benzophenones, and risk of endometriosis: results from the EndEA study.

AIM: To explore the relationship of urinary concentrations of different congeners of benzophenones and parabens with the utilization of cosmetics and personal care products (PCPs) and their impact on the risk of endometriosis, and to evaluate the influence of oxidative stress on associations found. METHODS: This case-control study comprised a subsample of 124 women (35 cases; 89 controls). Endometriosis was confirmed (cases) or ruled out (controls) by laparoscopy, with visual inspection of the pelvis and biopsy of suspected lesions (histological diagnosis). Urinary concentrations of benzophenone-1 (BP-1), benzophenone-3 (BP-3), 4-hydroxibenzophenone (4-OH-BP), methyl- (MeP), ethyl- (EtP), propyl- (PrP), and butyl-paraben (BuP), and biomarkers of oxidative stress [lipid peroxidation (TBARS) and total antioxidant power (TAP)] were quantified. Information was gathered on the frequency of use of cosmetics and PCPs. Associations between the frequency of cosmetics/PCP use, urinary concentrations of benzophenones and parabens, oxidative stress, and endometriosis risk were explored in logistic and linear multivariable regression analyses. RESULTS: The frequency of utilization of certain cosmetics and PCPs was significantly associated with urinary concentrations of benzophenones and parabens. After adjustment for potential confounders, the risk of endometriosis was increased in women in the second versus first terciles of MeP (OR = 5.63; p-value<0.001), BP-1 (OR = 5.12; p-value = 0.011), BP-3 (OR = 4.98; p-value = 0.008), and Æ©BPs (OR = 3.34; p-value = 0.032). A close-to-significant relationship was observed between TBARS concentrations and increased endometriosis risk (OR = 1.60, p-value = 0.070) and an inverse association between TAP concentrations and this risk (OR = 0.15; p-value = 0.048). Oxidative stress results did not modify associations observed between benzophenone/paraben exposure and endometriosis risk. CONCLUSIONS: Our findings indicate that the frequency of cosmetics and PCP utilization is a strong predictor of exposure to certain benzophenone and paraben congeners. These compounds may increase the risk of endometriosis in an oxidative stress-independent manner. Further studies are warranted to corroborate these findings.

Menstrual blood concentrations of parabens and benzophenones and related factors in a sample of Spanish women: An exploratory study.

AIM: To evaluate concentrations of parabens (PBs) and benzophenones (BzPs) in menstrual blood and explore related sociodemographic/lifestyle factors, and to compare between menstrual and peripheral blood concentrations in a subset of samples. MATERIAL AND METHODS: Concentrations of 4 PBs [methyl- (MeP), ethyl- (EtP), propyl- (PrP) and butyl-paraben (BuP)] and 6 BzPs [BzP-1, BzP-2, BzP-3, BzP-6, BzP-8 and 4-OH-BzP] were determined in menstrual blood from 57 women and in both menstrual and peripheral blood samples from 12 women, all healthy Spanish women of reproductive age. Socio-demographic characteristics and lifestyle habits [diet and use of cosmetics and personal care products (PCPs)] were gathered using an online questionnaire. Spearman correlation analysis was performed to examine the relationship between menstrual and peripheral blood concentrations, while multivariable linear regression was used to identify potential explanatory variables for menstrual PB and BzP concentrations. RESULTS: Globally, all menstrual blood samples had detectable levels of ≥3 compounds, and 52.6% of the samples contained ≥6 compounds. MeP, PrP, and BzP-3 were the most frequently detected compounds (detection frequencies >90.0%), with median concentrations of 1.41, 0.63, and 1.70 ng/mL of menstrual blood, respectively. Age, the use of PCPs, and consumption of some food items (meat, pasta, cheese, or dairy products) were related to the menstrual blood concentrations of some PBs/BzPs. Serum:menstrual blood ratios of PBs/BzPs ranged from 1.7 to 3.6, with no inter-matrix correlations. CONCLUSIONS: This study reveals, to our knowledge for the first time, the widespread presence of several PBs and BzPs in intimate contact with gynecological tissues, although their concentrations in menstrual blood were not correlated with those in peripheral blood from the same women. These results shed light on the information provided by the menstrual blood as a potential matrix for characterizing exposure to PBs and BzPs, whose consequences for women's reproductive health need to be addressed.

Anogenital distance and reproductive outcomes in 9- to 11-year-old boys: the INMA-Granada cohort study.

BACKGROUND: Studies examining the association of anogenital distance (AGD), a biomarker of prenatal androgen exposure, with sexual development in children are lacking. OBJECTIVE: To assess the association between AGD measures and reproductive outcomes, including puberty onset, testicular volume, reproductive hormone levels, and urogenital malformations in boys aged 9-11 years. MATERIALS AND METHODS: A cross-sectional study was conducted among children belonging to the Spanish Environment and Childhood (INMA) Project, a population-based birth cohort study. The present sample included 279 boys for whom data were available on AGD, pubertal stage, testicular volume, and relevant covariates. Out of the boys with AGD data, 187 provided a blood sample for hormone analysis. AGD was measured from the center of the anus to the base of the scrotum. Pubertal development was assessed according to Tanner stage of genital development (G1-G5), and testicular volume was measured with an orchidometer. RESULTS: After adjusting for potential confounders, logistic regression analysis showed that AGD was positively associated with testicular volume but not with Tanner stage (>G1 vs. G1), serum hormone levels, or undescended testis. Regardless of their age, body mass index, and Tanner stage (G1 or >G1), boys with longer AGD showed increased odds of a testicular volume >3 mL (OR = 1.06, 95%CI = 1.00-1.19 per 10% increment in AGD; and OR = 3.14, 95%CI = 0.99-9.94 for AGD >42 mm vs. <33 mm). DISCUSSION: Longer AGD was associated with testicular growth, an indicator of gonadarche, but not with other reproductive outcomes. CONCLUSIONS: Although AGD was positively associated with testicular volume, it remains unclear whether AGD predicts testis size at puberty or is related to puberty onset.

Thyroid status and its association with cognitive functioning in healthy boys at 10 years of age.

OBJECTIVE: Thyroid hormones (THs) are crucial for the correct maturation of the CNS and the neurodevelopment of the child. We aimed to investigate the association of TSH and free thyroxine (FT4) levels with cognitive functioning in children from the INMA-Granada cohort studied during their follow-up at the age of 9-11 years. DESIGN: We evaluated 300 children from the original cohort, which comprised 668 eligible mother-son pairs recruited at birth from 2000 to 2002 in Granada (Spain). METHODS: FT4 and TSH concentrations were measured, and cognitive development was assessed using neuropsychological tests (n=187). Children with chronic disease related to thyroid function and/or cognitive development were excluded. RESULTS: Median TSH and FT4 levels were 3.1 µIU/ml and 1.2 ng/dl respectively. In multivariable regression analyses adjusted for maternal and child characteristics, children with TSH levels in the top tertile had worse verbal comprehension and immediate and long-term recall. Children with FT4 levels in the top tertile had better attention and lower impulsivity and were at a lower risk of scoring below the 20th percentile in intelligence quotient (OR=0.24; 95% CI=0.08-0.74; P=0.013) and in abstract reasoning ability (OR=0.28; 95% CI=0.09-0.88; P=0.029). CONCLUSION: Our findings indicate that circulating THs and TSH may in the top tertile have an impact on cognitive functions; thus, higher TSH slightly but significantly increased the risk of a lower score in certain neuropsychological tests.