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

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

Decreased 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 control

Female rats in adulthood in estrus phase

Fernandez 2009

[79]

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 FSH mRNA expression. No significant change in serum LH and FSH Levels at 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

No significant change in LH and FSH mRNA expression at proestrus phase

Female offspring (F1) in adulthood

Xi 2011

[29]

Rat

Sprague-Dawley

8-week-old

Oral gavage

From GD1 to PND20

0.001 or 0.1 mg/kg bw/ day

After 90 days of exposure

Increased 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 estrus

The same adult female rats (8-week- old)

Lee 2013

[30]

Rat

Wistar

Adult pregnancy rats

Oral administration (drinking water)

From GD1 to PND21

3 μg/kg bw/Day

PND30

Increased serum LH levels. No significant change in serum FSH levels

Female offspring in prepubertal phase

Gamez 2015

[31]

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

Decreased basal and GnRH-stimulated serum LH levels at BPA 62.5–25.0 mg/kg bw/day.

Female pups

Fernandez 2009

[79]

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

During estrus

Decreased GnRH-stimulated (15′) serum LH levels at BPA 62.5–25.0 mg/kg bw/day during estrus

Female rats in adulthood

Fernandez 2009

[79]

Mouse

ICR

Adult female mice

Oral Administration

Proestrus after 4th/5th estrus

20 μg/kg bw/ day

During diestrus, proestrus and estrus

Increased serum LH and FSH levels during proestrus

The same adult female mice

Wang 2014

[78]

Mouse

ICR

Adult female mice

Injection into the right lateral ventricle

Proestrus after 4th/5th estrus

0.02, 0.2, 2,20 and 200nM/3μl

During diestrus, proestrus and estrus

Increased serum LH levels during proestrus

The same adult female mice

Wang 2014

[78]

Rat

Sprague-Dawley

Adult Female rats

Oral Administration

After two classic estrous cycles

50 mg/kg bw/day

6 consecutive weeks

Increased serum LH and FSH levels

The same adult female rats

Zhou 2014

[86]

Mice

C57BL/6J

Adult female mice

Oral administration

12–15 days (first 3 reproductive cycle)

50 μg/kg bw/ Day

51–54 days

No significant change in serum LH and FSH Levels

The same adult female mice

Moore- Ambriz 2015

[87]

Rat

Sprague- Dawley

Adult Female rats

Oral gavage

42 days

10 mg/kg bw/day

After the last treatment day, during diestrus

Decreased serum LH and FSH levels during diestrus

The same adult female rats

Zaid 2018

[88]

Rat

Wistar

Adult female

Subcutaneous Injection

From PND 90 to PND105

25 ng/kg/d and 5 mg/kg/ day

24 h after last treatment, during diestrus

No significant change in serum LH and FSH levels. Delay in LH surge during diestrus

The same adult female rats

Lòpez-Rodríguez 2019

[89]

Mouse

C57BL/6J

Adult second- pregnancy mice

Oral gavage

Pregnancy From GD15 to lactation (PND21) period

0.05 and 5 mg/kg bw/ day

During diestrus 5 weeks after BPA administration

No change in serum LH levels during diestrus

Female offspring in adulthood

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

Precluded the production of an E2-induced LH surge at 20 mg/kg bw/day during estrus

Female pups in adulthood from PND85 to 100

Monje 2010

[82]