Association of novel and legacy PFAS with reproductive hormones in women of child‑bearing age

Objective:To evaluate the legacy and novel per-and polyfluoroalkyl substances(PFAS)exposure in women of reproductive age,and to explore the effects on female reproductive hormones.Methods:We used cross-sectional data of 433 normal women of reproductive age from 2013 to 2015.Data of age,age at menarche,parity,BMI,education,and income were collected through questionnaires,serum samples were collected for reproductive hormones,and plasma samples for PFAS measurement by ultraperformance liquid chromatography-tandem mass spectrometer(UPLC-MS/MS).Multiple linear regression and quantile g-computation were adopted to analyze the association between PFAS and reproductive hormones.Results:The detection rates of 6:2 Cl-PFESA,8:2 Cl-PFESA and HFPO-DA in the plasma were 100%,99.8%and 99.9%,respectively.The median concentrations of these chemicals were 2.27 ng/mL,0.07 ng/mL and 0.03 ng/mL,respectively.Multiple linear regression analysis showed a positive association between branched PFOS[1m-PFOS(β=0.131,95%CI:0.021,0.242),br-PFOS(β=0.119,95%CI:0.005,0.234)]and progesterone.In addition,mixed exposure model suggested that PFAS had a positive association with progesterone(β=0.549,95%CI:0.323,0.774).Conclusion:In this study,a mixed exposure model was used to evaluate the combined effects of PFAS mixtures,reflecting the association between multiple environmental PFAS exposure and reproductive hormones,and a higher concentration of novel PFAS was found in women of reproductive age,confirming that PFAS exposure may be related to reproductive hormone disorders in women of reproductive age.

Association of Body Mass Index with Hypothalamus-Pituitary-Ovarian Axis Hormones in Infertile Women in the Niger Delta Region, Nigeria

Background: Infertility is well-known global health problem that has significant impacts on an individual, families and communities. Many modifiable lifestyle risk factors increase the risk of women to several reproductive disorders. Aim: This study established the relationship between obesity and Hypothalamic-Pituitary-Ovarian (HPO) axis hormones in infertile women in the Niger Delta Region, Nigeria. Methodology: Six hundred and twenty-six (626) women aged 18 - 40 years comprising of 513 obese infertile women and 113 non obese women who served as control were recruited for the study. Anthropometric measurements were taken and Body Mass Index was calculated. A non-fasting venous blood sample was collected from the women and analyzed for serum Estrogen, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), Progesterone, Inhibin B, and Prolactin using Enzyme linked immunosorbent assay method. Results: In the present study, the Body Mass Index of women with primary (1°) infertility is significantly (p < 0.05) higher than secondary (2°) infertility women. Whereas, women with 2° infertility were older and have a higher height than women with 1° infertility. The result revealed that serum estrogen, luteinizing hormone, follicle stimulating hormone and prolactin levels were significantly (p < 0.05) higher in the obese infertile women, while inhibin B and progesterone levels were significantly (p < 0.05) reduced in the obese infertile women compared to the control subjects. However, women with 1° infertility have a significantly higher LH and FSH levels than the 2° infertility women. Furthermore, the study revealed that hyperestrogenism is the most prevalent gonadal disorder in women with primary infertility and secondary infertility. The BMI of infertile women suffering Hyperestrogenism is significantly higher than any other female gonadal disorder. The result also showed that there is statistically significant positive correlation between BMI and Hypogonadism, Hypogonadotropic and Amenorrhoea in obese infertility women. While, no significant correlation between BMI and Hypergonadism and Hypergonadotropic was observed. Furthermore, there was a positive correlation between BMI and Hypothalamus-Pituitary Ovarian hormones, as BMI showed a positive correlation with LH, FSH, Estrogen, progesterone, and prolactin in women with primary and secondary infertility, while Inhibin B showed a negative correlation with BMI. Conclusion: There is a relationship between BMI and Hypothalamus-Pituitary Ovarian hormones, signifying that obesity could affect female reproduction and directly impact ovarian function. Therefore, body weight maintenance should be considered as a first line of management of Hypothalamus-Pituitary Ovarian hormonal related infertility.

月经周期中免疫球蛋白G N-糖基化的周期性变化

Immunoglobulin G(IgG)is the most abundant plasma glycoprotein and a prominent humoral immune mediator.Glycan composition affects the affinity of IgG to ligands and consequent immune responses.The modification of IgG N-glycosylation is considered to be one of the various mechanisms by which sex hormones modulate the immune system.Although the menstrual cycle is the central sex hormonerelated physiological process in most women of reproductive age,IgG N-glycosylation dynamics during the menstrual cycle have not yet been investigated.To fill this gap,we profiled the plasma IgG Nglycans of 70 healthy premenopausal women at 12 time points during their menstrual cycles(every 7 days for 3 months)using hydrophilic interaction ultra-performance liquid chromatography(HILIC-UPLC).We observed cyclic periodic changes in the N-glycosylation of IgG in association with the menstrual cycle phase and sex hormone concentration in plasma.On the integrated cohort level,the modeled average menstrual cycle effect on the abundance of IgG N-glycosylation traits was low for each trait,with the highest being 1.1%for agalactosylated N-glycans.However,intrapersonal changes were relatively high in some cases;for example,the largest difference between the minimum and maximum values during the menstrual cycle was up to 21%for sialylated N-glycans.Across all measurements,the menstrual cycle phase could explain up to 0.72%of the variation in the abundance of a single IgG glycosylation trait of monogalactosylation.In contrast,up to 99%of the variation in the abundance of digalactosylation could be attributed to interpersonal differences in IgG N-glycosylation.In conclusion,the average extent of changes in the IgG N-glycopattern that occur during the menstrual cycle is small;thus,the IgG N-glycoprofiling of women in large sample-size studies can be performed regardless of menstrual cycle phase.

EXPRESSIONS OF ESTROGEN OCCUPIED RECEPTOR（EoR） AND PROGESTERONEOCCUPIED RECEPTOR（PoR） AND C－erbB－2ONCOPROTEININ HUMANNASOPHAR

It is first reported here that estrogen occupied receptor(EoR)and progesterone occupied receptor (RoR)expressed in cancerous tissues (59.57% and 82.98% respectively)and morphologically normal epithlium(50 77.78% and 70-88.89%respectively) in nasoplharyngeal carcinomas(NPCs)with insignificant difference(P>0.05).Positive rates of EoR and PoR increased greatly in clinical stage Ⅲ and Ⅳ, compared with in Ⅱ(P<0.05), and exhibited insignificant difference between female cases and male ones(P>0.05).Positive rate of C-erbB-2 was 19.15% in cancerous cells, and 9.68% in stage Ⅲand 66.67% in Ⅳin NPCs(P<0.05).Significant difference of C-erbB-2expression was observed between bilateral cervical lymph node metastasis(BCLM)and unilateral ones(P<0.05)but not for EoR or PoR(P>0.05)These findings suggest that EoR or PoR may be correlated with aggravation but not genesis and node metastasis in NPCs and that C-erbB-2may be correlated with aggravation and promotion of formation of node metastasis in NPCs.