摘要：Industrial chemicals such as persistent organic pollutants (POPs) have been associated with reduced fertility in women, including longer time-to-pregnancy (TTP), higher odds for infertility, and earlier reproductive senescence. Fertility is highly dependent on the ovarian reserve, which is composed of a prenatally determined stock of non-growing follicles. The quantity and quality of the follicles decline with age, thereby eventually leading to menopause. In the clinical setting, assessing ovarian reserve directly through the histological analysis of follicular density in ovaries is not practical. Therefore, surrogate markers of ovarian reserve, such as serum anti-Müllerian hormone (AMH) are typically used. Here, we studied associations between chemical exposure and ovarian reserve in a cohort of pregnant women undergoing elective caesarean section (n = 145) in Stockholm, Sweden. Full data (histological, clinical, serum) were available for 50 women. We estimated the size of the reserve both directly by determining the density of follicles in ovarian cortical tissue samples, and indirectly by measuring AMH in associated serum samples. Concentrations of 9 organochlorine pesticides (OCPs), 10 polychlorinated biphenyls (PCBs), 3 polybrominated diphenylethers (PBDEs) and 9 perfluoroalkyl substances (PFAS) were determined in serum, and clinical data were retrieved from electronic medical records. Healthy follicle densities (median 0, range 0–193 follicles/mm 3 ) and AMH levels (median 2.33 ng/mL, range 0.1–14.8 ng/mL) varied substantially. AMH correlated with the density of growing follicles. Twenty-three chemicals detected in more than half of the samples were included in the analyses. None of the chemicals, alone or as a mixture, correlated with AMH, growing or atretic follicles. However, HCB, transnonachlor, PCBs 74 and 99 were associated with decreased non-growing follicle densities. HCB and transnonachlor were also negatively associated with healthy follicle density. Further, mixture of lipophilic POPs (PBDE 99, p,p’-DDE, and PCB 187) was associated with lower non-growing follicle densities. In addition, exposure to HCB, p,p’-DDE, and mixture of OCPs were significantly associated with higher odds of infertility. The results suggest that exposure to chemicals may reduce the size of ovarian reserve in humans, and strongly encourage to study mechanisms behind POP-associated infertility in women in more detail.
关键词：Ovary ; Ovarian reserve ; Anti-Müllerian hormone ; Female fertility ; Persistent organic pollutants ; AFC antral follicle count ; AMH anti-Müllerian hormone ; BMI body mass index ; CI confidence interval ; CV coefficient of variation ; FSH follicle stimulating hormone ; GC–MS/MS gas chromatography; tandem mass spectrometry ; GM; geometric mean HCB; hexachlorobenzene ; HCH hexachlorocyclohexane ; IQR interquartile range ; LA lipid-adjusted ; LC-MS/MS liquid chromatography/triple quadrupole mass spectrometry ; LOD limit of detection ; LOQ limit of quantification ; OCP organochlorine pesticide ; OR odds ratio ; PBDE polybrominated diphenyl ethers ; PCB polychlorinated biphenyl ; PeCB pentachlorobenzene ; PFAS perfluoroalkyl substances ; PFDA perfluorodecanoic acid ; PFDoA perfluorododecanoic acid ; PFHpA perfluoroheptanoic acid ; PFHxS perfluorohexane sulfonic acid ; PFHxA perfluorohexanoic acid ; PFNA perfluorononanoic acid ; PFOS perfluorooctanesulfonic acid ; PFOA perfluorooctanoic acid ; PFUnDA; perfluoroundecanoic acid p;p’-DDE dichlorodiphenyldichloroethylene ; p;p’-DDT dichlorodiphenyltrichloroethane ; POP persistent organic pollutant ; TTP time-to-pregnancy ; WQS weighted quantile sum
