Persistent organic pollutants and the size of ovarian reserve in reproductive-aged women

https://doi.org/10.1016/j.envint.2021.106589Get rights and content
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Highlights

  • Ovarian reserve measured directly and indirectly in pregnant women.

  • Mixture of at least 14 POPs found in all women.

  • Serum AMH correlated with growing, but not non-growing follicle densities.

  • No associations between serum chemicals, AMH, growing or atretic follicle densities.

  • Lipophilic POPs were associated with lower ovarian reserve and infertility.

Abstract

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/mm3) 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.

Keywords

Ovary
Ovarian reserve
Anti-Müllerian hormone
Female fertility
Persistent organic pollutants

Abbreviations

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

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1

Contributed equally to this work.