Per- and polyfluoroalkyl substances (PFASs) are widely used in China, but little is known about the association between prenatal PFASs exposure and fetal reproductive development as well as its potential mechanism. We investigated the effects of cord blood PFASs on fetal reproductive hormones and its potential mechanism in relation to steroidogenic enzymes. Ten selected PFASs (n = 351) including PFOS, PFOA, PFBS, PFDA, PFDoA, PFHpA, PFHxS, PFNA, PFOSA, and PFUA, and two reproductive hormones estradiol (E2) (n = 351) and testosterone (T) (n = 349) were measured in 351 cord blood serum samples from a Chinese birth cohort between 2010 and 2013. Three steroidogenic enzymes including P450arom (n = 125), 3β-HSD1 (n = 123), and 17β-HSD1 (n = 116) were measured in 125 placental tissue samples. Linear regression tested the associations between cord blood PFASs and reproductive hormones in cord blood. Mediation analysis assessed the role of placental steroidogenic enzymes between cord blood PFASs and reproductive hormones. The positive associations between PFOA, PFHxS and E2 levels, PFOS, PFUA, PFNA and T levels, and PFOS, PFUA and T/E2 ratio were significant. PFUA, PFNA, PFDA, PFHxS, and ∑PFASs were associated with higher P450arom levels. PFHxS was also associated with increased 3β-HSD1 and 17β-HSD1 levels. These associations were more pronounced in females than males when stratified by gender. Furthermore, 17β-HSD1 demonstrated mediating effects in the positive association between cord blood PFHxS and E2 levels in females. Our findings suggested the potential impacts of cord blood PFASs on fetal reproductive hormones, in which steroidogenic enzymes may play important roles. These associations were more pronounced in females than males.

Background: The association of sleep onset time and duration with cardiometabolic health is not well characterized. Methods and Results: This study included 6696 adults aged 20 to 80 years from the NHANES (National Health and Nutrition Examination Study) 2015 to 2018. Participants were categorized into 9 groups according to the cross‐tabulation of sleep onset time (<22:00 [early], 22:00–23:59 [optimal], and ≥24:00 [late]) and duration (<7 hours [insufficient], 7–8 hours [sufficient], and ≥9 hours [excessive]), with optimal sleep onset time and sufficient duration as the reference. The primary outcomes included hypertension, hypertriglyceridemia, low high‐density lipoprotein cholesterol, hyperglycemia, central obesity, and metabolic syndrome. Inappropriate sleep onset time and sleep duration were associated with increased odds of hypertension, hypertriglyceridemia, and metabolic syndrome, especially among participants aged 40 to 59 years. Compared with men reporting optimal onset and sufficient duration, men reporting optimal onset with excessive duration (odds ratio [OR]: 2.01 [95% CI, 1.12–3.58]) and late onset with insufficient duration (OR, 1.74 [95% CI, 1.13–2.68]) had higher odds of metabolic syndrome. Compared with women reporting optimal onset and sufficient duration, women reporting optimal onset and insufficient duration (OR, 1.61 [95% CI, 1.11–2.32]) and early onset and excessive duration (OR, 2.16 [95% CI, 1.30–3.57]) had higher odds of hypertension, and women reporting late onset and excessive duration (OR, 5.64 [95% CI, 1.28–6.77]) were at the highest odds of hypertriglyceridemia. Conclusions: Late sleep onset as well as insufficient or excessive sleep duration are associated with adverse cardiometabolic outcomes, particularly in participants aged 40 to 59 years.