Table 3 Bisphenol A and hypothalamus-pituitary-ovary (HPO) axis: ovary
Source | Strain | Age | Exposure route | Time of exposure | Doses | Time of observation | Outcome | Outcome observed in | Reference n° | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
Experimental studies in vitro and ex-vivo | Rats | Ovarian theca- interstitial (T-I) obtained from Sprague– Dawley rats | 28–30 days old | In vitro administration | 72 h | BPA low concentration 10–7 M and high concentration from 10 to 4 M to 10–6M | After 72 h | Increase cholesterol side-chain cleavage enzyme (P450scc) and 17 alpha-hydroxylase/17,20 lyase (P450c17) mRNA at all BPA concentrations tested. Increased StAR mRNA expression and T secretion at BPA 10–5 and 10–4M | Ovarian theca- interstitial (T-I) obtained from Sprague– Dawley rats | Zhou 2008 | [28] |
Rats | Granulosa cells obtained from Sprague– Dawley rats | 28–30 days old | In vitro administration | 72 h | from 10 to 4 M to 10–7M | After 72 h | Increased StAR mRNA and P levels in cell media from BPA 10–7 to 10–5 M. Decreased P levels in cell media at BPA 10–4 M. E2 levels dose-dependently decreased while aromatase mRNA increased after BPA at 10–7 to 10–4M | Granulosa cells obtained from Sprague– Dawley rats | Zhou 2008 | [28] | |
Mice | FVB | Adult female | Ex vivo administration in antral follicles | PND32 | 4.4, 44, and 440 μM | 120 h | Decreased levels of P and E2 in cell media at 440 μM of BPA. Decreased StAR and 3ß-HSD mRNA expression in antral follicules after BPA exposure of 440 μM | Antral follicules of adult female mice | Peretz 2011 | [32] | |
Human | Luteinized granulosa cells | Fertile and infertile patients < 38 years old | In vitro Administration | 48 h | 0.2, 0.02,2.0, 20 μg/ml | After 48 h | P and E2 reduced secretion in cell media. P450scc, 3ß-HSD and aromatase mRNA expression reduced at BPA higher concentrations. | Luteinized granulosa cells | Mansur 2016 | [33] | |
Mice CD-1 | Antral follicles | PND32-PND35 | In vitro administration | 24h-96h | 1.0. 10, 100μg/ml | 24h-96h | Lack of cholesterol conversion to Pregnenologne and consequently decreased of CYP11a1 and StAR expression. Decrease of androsteneidione, T, and E2 levels | Antral follicles | Peretz 2013 | [34] | |
Experimental studies in vivo | Mouse | CD-1 | Adult pregnant mice | Oral gavage | Cohort A: From GD1 to PND20 | 12, 25 and 50 mg/kg bw/day | PND50 | Increased serum E2 levels associated with mRNA and protein P450scc and aromatase expressions up- regulation after BPA exposure to 12, 25 and 50 mg/kg bw/day in proestrus phase | Female offspring (F1) in adulthood | Xi 2011 | [29] |
Mouse | CD-1 | Female pups (F1) | Oral gavage | Cohort B: From PND20 to PND49 | 25 and 50 mg/kg bw/day | PND50 | Increased serum E2 levels wherease no change in CYP mRNA expression at proestrus phase | Female offspring (F1) in adulthood | Xi 2011 | [29] | |
Rat | Sprague- Dawley | 8-week-old | Oral gavage | 90 days | 0.001 or 0.1 mg/kg bw/day | After 90 days of exposure during estrus | Decreased serum E2 levels. Decreased aromatase protein expression in granulosa cells in particular after BPA exposure of 0.001 mg/kg bw/day. Downregulation of StAR protein expression after BPA exposure of 0.001 or 0.1 mg/kg bw/day | The same adult female rats (8-week- old) | Lee 2013 | [30] | |
Rat | Wistar | Adult pregnant rats | Oral administration (drinking water) | From GD1 to PND21 | 3 μg/kg bw/day | PND30 | Increased serum E2 levels | Female offspring (F1) in prepubertal phase | Gamez 2015 | [31] | |
Mice | ICR | Adult Female mice | Oral administration | 6h | 20μg/kg bw/ day | Diestrus, proestrus and estrus | Increased serum E2 levels during proestrus | The same adult mice | Wang 2014 | [78] | |
Mice | ICR | Adult female mice | Injection into the right lateral ventricle | 6h | 0.02, 0.2, 2,20 and 200 nM/3μl | Diestrus, proestrus and estrus | Increased serum E2 levels during proestrus | The same adult mice | Wang 2014 | [78] | |
Rat | Sprague-Dawley | Female pups | Subcutaneous Injection | From PND1 to PND10 | 6.2–2.5 mg/kg bw/day and 62.5–25.0 mg/ kg bw/day | PND13 | Increased levels of serum E2 and T, and decreased P serum levels | The same rats in adulthood | Fernandez 2010 | [80] | |
Rats | Sprague-Dawley | Adult female | Oral administration | After two classic estrous cycles | 50 mg/kg bw/ day | 6 consecutive weeks | Increased mRNA and protein expression of FSHR | The same adult female rats | Zhou 2014 | [86] | |
Mice | C57BL/6 J | 39 days old | Oral administration | 12–15 days (first 3 reproductive cycle) | 50 μg/kg bw/ day | At third proestrus | No significant change in serum E2 levels | The same adult female mice (39-days-old) | Moore-Ambriz 2015 | [87] | |
Ewes | Suffolk | N.R. | Injection | From GD30 to GD90 | 0.5 mg/k | From GD30 to GD90 | Prenatal BPA increased Cyp19 and 5α-reductase expression in day 65, but not day 90, ovaries. Fetal ovarian microRNA expression was altered by prenatal BPA with 45 down-regulated at day 65 and 11 down-regulated at day 90 of gestation. These included microRNAs targeting Sry- related high-mobility-group box (SOX) family genes, kit ligand, and insulin-related genes | Female offspring at fetal day 65 and at fetal day 90 | Veiga- Lopez 2013 | [90] | |
Rat | Sprague- Dawley | 28 days-old | Oral gavage | 42 days | 10 mg/kg bw/ day | After the last treatment day, during diestrus | Slight but not significant increase of E2 serum levels and reduction of P serum levels | The same adult female rats (70-days-old) | Zaid 2018 | [88] | |
Mouse | C57BL/6 J | Adult second- pregnancy mice | Oral gavage | Pregnancy GD15) and lactation (PND21) period | 0.05 and 5 mg/kg bw/day | During diestrus 5 weeks after BPA administration | Increased serum E2 levels in diestrus | Female offspring in adulthood | Naule 2014 | [81] |