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

From: Bisphenol A: an emerging threat to female fertility

 SourceStrainAgeExposure routeTime of exposureDosesTime of observationOutcomeOutcome observed inReference n° 
Experimental studies in vitro and ex-vivoRatSprague-DawleyFemale PupsSubcutaneous InjectionFrom PND1 to PND106.2–2.5 mg/kg bw/day and 62.5–25.0 mg/kg bw/dayPND13Increased GnRH pulsatility in hypothalamic explantsAdult femaleFernandez 2009[79]
RatSprague-DawleyFemale pupsSubcutaneous InjectionFrom PND1 to PND105, 50 and 500 μg/kg bw/dayPND13Adult female rats postnatally exposed to BPA presented alterations in GnRH secretion, as demonstrated by a decrease in the IPIAdult female and female pupsFernandez 2010[80]
Experimental studies in vivoMouseCD-1Adult pregnant miceOral gavageFrom GD1 to PND2012, 25 and 50 mg/kg bw/ dayPND50Increased Kiss1 and GnRH mRNA expression at 25–50 mg/Kg bw/day during proestrus phaseFemale offspring (F1) in adulthoodXi 2011[29]
MouseCD-1Female pupsOral gavageFrom PND20 to PND4925 and 50 mg/kg bw/ dayPND50No effect on Kiss1 and GnRH mRNA expression during proestrus phaseFemale offspring (F1) in adulthoodXi 2011[29]
MouseICRAdult female miceOral administrationProestrus after 4th/5th estrus cycle20 μg/kg bw/day6 h after BPAadministrationIncreased GnRH mRNA expression in POA as well as Kiss1 mRNA in AVPV, but not Kiss1 in ARC during proestrusThe same adult female mice (12- week-old)Wang 2014[78]
MouseICRAdult female miceInjection into the right lateral ventricleProestrus after 4th/5th estrus cycle0.02, 0.2, 2.0, 20.0, and 200.0 nM/3 ml6 h after BPA administrationIncreased GnRH mRNA expression in POA. Increased Kiss1 mRNA in AVPV and decreased Kiss1 mRNA in ARC during proestrusThe same adult female mice (12- week-old)Wang 2014[78]
MouseC57BL/6JAdult second-pregnancy damsOral gavagePregnancy (gestational day 15) and lactation (PND21) period0.05 and 5 mg/kg bw/ dayDuring diestrus 5 weeks after BPA administrationIncreased Kisspeptin protein expression in RP3V but no change in GnRH protein in the POA during diestrusFemale offspring in adulthood (from 8 weeks of age)Naule 2014[81]
RatWistar-derived strainFemale Pups (F1)Subcutaneous InjectionFrom PND1 to PND70.05 and 20 mg/kg bw/ dayDuring estrus from PND85 to PND100Increased GnRH mRNA levels at 0.05 mg/kg bw/day and decreased at 20 mg/kg bw/day during estrusFemale offspring in adulthood (PND100)Monje 2010[82]
RatLong EvansFemale Pups (F1)Subcutaneous InjectionFrom PND1 to PND350 μg/kg bw/ day and 50 mg/kg bw/ day7 weeks after PND148No impairement of GnRH neurons activationFemale pups (F1)Adewale 2009[83]
MonkeyMacaca mulattaPubertal femaleInfusion in stalk-median eminenceDuring follicular phase0.1, 1 and 10 nMEach 20’ for 240’ after BPA exposureDecreased GnRH and Kisspeptin secretion and pulse after 10nM of BPA at pubertyPubertal femaleKurian 2015[84]
Sheepn.r.Adult pregnant sheepSubcutaneous InjectionsFrom GD 30 to GD905 mg/kg/dayDuring estrus in sheep at 21 months of ageDecreased GnRH mRNA expression in hypothalamus. Increased of ERα mRNA expression and reduced ERβ mRNA expression in POA.Female Offspring in adulthoodMahoney 2010[85]