Background Fetal growth restriction (FGR) is not only a major determinant of perinatal morbidity and mortality but also leads to adverse health effects in later life. Over the past decade, numerous studies have indicated that maternal exposure to ambient air pollution has been a risk factor for abnormal fetal growth in developed countries where PM 2.5 levels are relatively low. However, studies in highly polluted regions, such as China, and studies that rely on assessments in utero are scarce. Methods A total of 7965 women were selected from 11,441 women from the Shanghai Maternity and Infant Living Environment (SMILE) cohort who were pregnant between January 1, 2014, and April 30, 2015. From January 1, 2014, to April 30, 2015, weekly average PM 2.5 values from 53 monitors were calculated and the inverse distance weighted (IDW) method was used to create a Shanghai pollution surface map according to the participants residential addresses. Individual exposure was the average PM 2.5 value of every gestational week between the first gestational week and one week before the ultrasound measurement date (the range of measurements per participant was 1 to 10). Repeated fetal ultrasound measurements during gestational weeks 14~40 were selected. The estimated fetal weight (EFW) was calculated by biparietal diameter (BPD), abdominal circumference (AC), and femur length (FL) formulas. In total, 29,926 ultrasound measurements were analysed. Demographic variables, other pollutants (SO 2 , NO 2 , PM 10 and O 3 ) and relative humidity and temperature were controlled for potential confounding through generalized estimating equations (GEE). Results The full model showed that with each 10 μg/m 3 increase in PM 2.5 exposure, the means (mm) of AC, BPD, FL decreased by 5.48 (− 9.06, − 1.91), 5.57 (− 6.66, − 4.47), and 5.47 (− 6.39, − 4.55), respectively; the mean EFW decreased by 14.49 (− 16.05, − 13.49) grams by Hadlock’s third formula and 13.56 (− 14.71, − 12.50) grams by Shepard’s formula with each 10 μg/m 3 increase in PM 2.5 exposure. Conclusions A negative correlation existed between maternal PM 2.5 exposure during pregnancy and fetal growth indicators, which may increase the risk of fetal growth restriction. Electronic supplementary material The online version of this article (10.1186/s12940-019-0485-3) contains supplementary material, which is available to authorized users.

As the main constituent cells of the human placenta, trophoblasts proliferate, differentiate, and invade the uterine endometrium via a series of processes, which are regulated exquisitely through intercellular signaling mediated by hormones, cytokines, and growth factors. Programmed cell death ligand 1 (PD-L1) is a biomarker of the response to immune checkpoint inhibitors and can regulate maternal-fetal immune tolerance during pregnancy progression. Recently, it was found that PD-L1 may regulate obstetric complications by affecting the function of trophoblasts. Therefore, we examined the expression and localization of PD-L1 in the human placenta and observed the effects of PD-L1 on trophoblasts migration and invasion in both the trophoblasts line HTR-8/SVneo and an extravillous explant culture model. Finally, we explored the molecular mechanisms underlying PD-L1-regulated trophoblasts migration and invasion through RNA sequencing and bioinformatics analysis. Our data showed that PD-L1 was mainly expressed in syncytiotrophoblasts and that its protein levels increased with gestational age. Interestingly, the protein expression of PD-L1 was significantly decreased in placentas from pregnancies with preeclampsia compared with normal placentas. Importantly, the migration and invasion abilities of trophoblasts were significantly changed after knockdown or overexpression of PD-L1 in HTR-8/SVneo cells and an extravillous explant culture model, which was partially mediated through the transcription factor PU.1 (encoded by Spi1)-regulated Rho GDP-dissociation inhibitor beta (ARHGDIB) expression. These results suggested that PD-L1 was highly involved in the regulation of trophoblasts migration and invasion, providing a potential target for the diagnosis and treatment of placenta-derived pregnancy disorders.

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