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Table 2 Bisphenol A and hypothalamus-pituitary-ovary (HPO) axis: pituitary

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/dayPND13Decreased basal and GnRH-stimulated LH levels in medium of adult anterior pituitary cell cul tures. Adult anterior pituitary cell cultures treated with BPA 6.2–2.5 mg/kg bw/day showed rapid and transient activation of ERK1/2 com pared to controlFemale rats in adulthood in estrus phaseFernandez 2009[79]
Experimental studies in vivoMouseCD-1Adult pregnant miceOral gavageCohort A: from GD1 to PND2012, 25 and 50 mg/kg bw/dayPND50Increased FSH mRNA expression. No significant change in serum LH and FSH Levels at proestrus phaseFemale offspring (F1) in adulthoodXi 2011[29]
MouseCD-1Female pups (F1)Oral gavageCohort B: from PND20 to PND4925 and 50 mg/kg bw/dayPND50No significant change in LH and FSH mRNA expression at proestrus phaseFemale offspring (F1) in adulthoodXi 2011[29]
RatSprague-Dawley8-week-oldOral gavageFrom GD1 to PND200.001 or 0.1 mg/kg bw/ dayAfter 90 days of exposureIncreased serum LH levels and LH protein content after BPA exposure of 0.001 and 0.1 mg/kg bw/ day. No significant change in serum FSH levels and FSH protein expression during estrusThe same adult female rats (8-week- old)Lee 2013[30]
RatWistarAdult pregnancy ratsOral administration (drinking water)From GD1 to PND213 μg/kg bw/DayPND30Increased serum LH levels. No significant change in serum FSH levelsFemale offspring in prepubertal phaseGamez 2015[31]
RatSprague-DawleyFemale pupsSubcutaneous InjectionFrom PND1 to PND106.2–2.5 mg/kg bw/day and 62.5–25.0 mg/kg bw/dayPND13Decreased basal and GnRH-stimulated serum LH levels at BPA 62.5–25.0 mg/kg bw/day.Female pupsFernandez 2009[79]
RatSprague-DawleyFemale pupsSubcutaneous InjectionFrom PND1 to PND106.2–2.5 mg/kg bw/day and 62.5–25.0 mg/kg bw/dayDuring estrusDecreased GnRH-stimulated (15′) serum LH levels at BPA 62.5–25.0 mg/kg bw/day during estrusFemale rats in adulthoodFernandez 2009[79]
MouseICRAdult female miceOral AdministrationProestrus after 4th/5th estrus20 μg/kg bw/ dayDuring diestrus, proestrus and estrusIncreased serum LH and FSH levels during proestrusThe same adult female miceWang 2014[78]
MouseICRAdult female miceInjection into the right lateral ventricleProestrus after 4th/5th estrus0.02, 0.2, 2,20 and 200nM/3μlDuring diestrus, proestrus and estrusIncreased serum LH levels during proestrusThe same adult female miceWang 2014[78]
RatSprague-DawleyAdult Female ratsOral AdministrationAfter two classic estrous cycles50 mg/kg bw/day6 consecutive weeksIncreased serum LH and FSH levelsThe same adult female ratsZhou 2014[86]
MiceC57BL/6JAdult female miceOral administration12–15 days (first 3 reproductive cycle)50 μg/kg bw/ Day51–54 daysNo significant change in serum LH and FSH LevelsThe same adult female miceMoore- Ambriz 2015[87]
RatSprague- DawleyAdult Female ratsOral gavage42 days10 mg/kg bw/dayAfter the last treatment day, during diestrusDecreased serum LH and FSH levels during diestrusThe same adult female ratsZaid 2018[88]
RatWistarAdult femaleSubcutaneous InjectionFrom PND 90 to PND10525 ng/kg/d and 5 mg/kg/ day24 h after last treatment, during diestrusNo significant change in serum LH and FSH levels. Delay in LH surge during diestrusThe same adult female ratsLòpez-Rodríguez 2019[89]
MouseC57BL/6JAdult second- pregnancy miceOral gavagePregnancy From GD15 to lactation (PND21) period0.05 and 5 mg/kg bw/ dayDuring diestrus 5 weeks after BPA administrationNo change in serum LH levels during diestrusFemale offspring in adulthoodNaule 2014[81]
RatWistar-derived strainFemale Pups (F1)Subcutaneous InjectionFrom PND1 to PND70.05 and 20 mg/kg bw/ dayDuring estrus from PND85 to PND100Precluded the production of an E2-induced LH surge at 20 mg/kg bw/day during estrusFemale pups in adulthood from PND85 to 100Monje 2010[82]