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Table 1 Bisphenol A and hypothalamus-pituitary-ovary (HPO) axis: hypothalamus

From: Bisphenol A: an emerging threat to female fertility

  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]