Table 1 Bisphenol A and hypothalamus-pituitary-ovary (HPO) axis: hypothalamus
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 | 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 GnRH pulsatility in hypothalamic explants | Adult female | Fernandez 2009 | [79] |
Rat | Sprague-Dawley | Female pups | Subcutaneous Injection | From PND1 to PND10 | 5, 50 and 500 μg/kg bw/day | PND13 | Adult female rats postnatally exposed to BPA presented alterations in GnRH secretion, as demonstrated by a decrease in the IPI | Adult female and female pups | Fernandez 2010 | [80] | |
Experimental studies in vivo | Mouse | CD-1 | Adult pregnant mice | Oral gavage | From GD1 to PND20 | 12, 25 and 50 mg/kg bw/ day | PND50 | Increased Kiss1 and GnRH mRNA expression at 25–50 mg/Kg bw/day during proestrus phase | Female offspring (F1) in adulthood | Xi 2011 | [29] |
Mouse | CD-1 | Female pups | Oral gavage | From PND20 to PND49 | 25 and 50 mg/kg bw/ day | PND50 | No effect on Kiss1 and GnRH mRNA expression during proestrus phase | Female offspring (F1) in adulthood | Xi 2011 | [29] | |
Mouse | ICR | Adult female mice | Oral administration | Proestrus after 4th/5th estrus cycle | 20 μg/kg bw/day | 6 h after BPAadministration | Increased GnRH mRNA expression in POA as well as Kiss1 mRNA in AVPV, but not Kiss1 in ARC during proestrus | The same adult female mice (12- week-old) | Wang 2014 | [78] | |
Mouse | ICR | Adult female mice | Injection into the right lateral ventricle | Proestrus after 4th/5th estrus cycle | 0.02, 0.2, 2.0, 20.0, and 200.0 nM/3 ml | 6 h after BPA administration | Increased GnRH mRNA expression in POA. Increased Kiss1 mRNA in AVPV and decreased Kiss1 mRNA in ARC during proestrus | The same adult female mice (12- week-old) | Wang 2014 | [78] | |
Mouse | C57BL/6J | Adult second-pregnancy dams | Oral gavage | Pregnancy (gestational day 15) and lactation (PND21) period | 0.05 and 5 mg/kg bw/ day | During diestrus 5 weeks after BPA administration | Increased Kisspeptin protein expression in RP3V but no change in GnRH protein in the POA during diestrus | Female offspring in adulthood (from 8 weeks of age) | Naule 2014 | [81] | |
Rat | Wistar-derived strain | Female Pups (F1) | Subcutaneous Injection | From PND1 to PND7 | 0.05 and 20 mg/kg bw/ day | During estrus from PND85 to PND100 | Increased GnRH mRNA levels at 0.05 mg/kg bw/day and decreased at 20 mg/kg bw/day during estrus | Female offspring in adulthood (PND100) | Monje 2010 | [82] | |
Rat | Long Evans | Female Pups (F1) | Subcutaneous Injection | From PND1 to PND3 | 50 μg/kg bw/ day and 50 mg/kg bw/ day | 7 weeks after PND148 | No impairement of GnRH neurons activation | Female pups (F1) | Adewale 2009 | [83] | |
Monkey | Macaca mulatta | Pubertal female | Infusion in stalk-median eminence | During follicular phase | 0.1, 1 and 10 nM | Each 20’ for 240’ after BPA exposure | Decreased GnRH and Kisspeptin secretion and pulse after 10nM of BPA at puberty | Pubertal female | Kurian 2015 | [84] | |
Sheep | n.r. | Adult pregnant sheep | Subcutaneous Injections | From GD 30 to GD90 | 5 mg/kg/day | During estrus in sheep at 21 months of age | Decreased GnRH mRNA expression in hypothalamus. Increased of ERα mRNA expression and reduced ERβ mRNA expression in POA. | Female Offspring in adulthood | Mahoney 2010 | [85] |