# Maternal-Foetal Effects of Exposure to Bisphenol A: Outcomes and Long-Term Consequences
## 5 Maternal-Foetal Effects of BPA
### Foetal Reproductive Function
Additionally, human BeWo trophoblast cell lines treated with BPA were also used to analyse the expression of oestrogen receptors, key enzymes for oestrogen synthesis, BCRP and DNA methyltransferases, as well as to investigate cell apoptosis. Overall, the results of this study showed increased BPA and oestrogen levels and reduced BCRP expression in the placentae from pregnancies diagnosed with foetalgrowth restriction, and in BPA-treated BeWo cells, there was also a reduction in BCRP mRNA and protein expression, increased oestrogen production involving enzymes for oestrogen synthesis, and the silencing of BCRP, which led to increased apoptosis. The authors concluded that the BPA accumulation in the placenta might lead to BCRP downregulation, and in BeWo cells, BPA is involved with oestrogen production and cell apoptosis through oestrogen receptors upregulation, culminating in foetal growth restriction [77]. On the other hand, two studies found opposite results. In a Spanish study, 488 mother-child pairs were recruited to investigate whether prenatal exposure to BPA was associated with foetal growth. For this, maternal urine samples were collected at approximately 12- and 32-weeks' gestation (first and third trimesters) for BPA quantification, and foetal ultrasound was used to assess femur length, head circumference, abdominal circumference and biparetal diameter. At the time of delivery, weight, length and head circumference were also measured, and the placentas were collected and measured to estimate the growth in utero. The results showed no significant associations between BPA and foetal/birth parameters [78]. Similarly, [PERSON] and co-workers found no association between maternal BPA exposure and foetal growth, even with four time-points urine collection and ultrasound scans, for BPA quantification and growth parameters measurement, respectively [36]. In a Danish study, 88 pregnant women with a singleton were recruited upon amniocentesis to investigate the connection between maternal EDC exposure and birth parameters. For this, urine samples were collected from the pregnant women after amniocentesis (between 12 and 36 weeks gestation) for BPA quantification. When correlated with newborns' birth size parameters (birth weight, length and head/abdominal circumferences), there was an overall significant decrease with increasing BPA exposure in male infants only. These results indicate that maternal BPA exposure has a negative sex-specific effect on infants' birth size [79]. In order to compare the effects of different bisphenol exposures on birth size, [PERSON] and colleagues quantified BPA, BPF and BPS in maternal urine collected in each trimester of pregnancy. From the results of the 845 volunteers, although the concentrations of BPA in urine were higher than those of BPF and BPS, no significant differences in birth parameters were found; only BPF and BPS had an inverse association with birth weight, length and ponderal index [80]. These results suggest that despite being substitutes, these compounds may have similar or worse adverse effects than BPA. In an attempt to use new quantification methods, [PERSON] and colleagues conducted an investigation where newborn dried blood spots were used to measure neonatal exposure to EDCs. Specifically, a total of 3111 newborn infants (2071 singleton and 1040 twins) were enrolled in the study, of whom five drops of whole blood were taken from a heel stick. Additionally, gestational age, birthweight, length, head circumference and ponderal index (kg/m\({}^{3}\)) were also measured. When comparing BPA levels with birth parameters, unlike the previous study, there was a negative association with gestational age and birthweight in twins, while in singletons, a positive association was found for ponderal index, i.e., with neonatal adiposity [81]. In a different study, amniotic fluid from 35 pregnant women was collected to study the influence of BPA exposure on abnormal foetal growth velocity.