Implications of a combined perinatal exposure to BPA and BP-3 for offspring folliculogenesis and ovarian function in mice

Article Experimental

Implications of a combined perinatal exposure to BPA and BP-3 for offspring folliculogenesis and ovarian function in mice

Elisabeth Krieger ^ab1, Florence Fischer ^abc1, Julia Howanski ^ab, Marita Wagner ^a, Federica Romanelli ^ab, Beate Fink ^a, Mario Bauer ^a, Anne Schumacher ^abd, Tobias Kretschmer ^abd2, Ana C. Zenclussen ^abde2

a Department of Environmental Immunology, Helmholtz-Center for Environmental Research – UFZ, Permoserstrasse 15, Leipzig 04318, Germany

b Perinatal Immunology, Saxonian Incubator for Clinical Translation (SIKT), Medical Faculty, Leipzig University, Philipp-Rosenthal-Strasse 55, Leipzig 04103, Germany

c Institute for Clinical Immunology, Leipzig University, Johannisallee 30, Leipzig 04103, Germany

d Leipzig Reproductive Health Research Center (LE-REP), Leipzig University, Liebigstrasse 20a, Leipzig 04103, Germany

e German Center for Child and Adolescent Health (DZKJ), partner site Leipzig/Dresden, Germany

ARTICLE INFO
Edited by Dr G Liu
Keywords:
Endocrine disrupting chemicals
Bisphenol A
Benzophenone-3
Folliculogenesis
Ovarian function
Fertility

Highlights

•BPA and BP-3 exposure impact on PMSG and hCG-induced folliculogenesis and atresia.
•Exposed offspring show changes in ovarian gene expression and NK cell number.
•BPA + BP-3 exposure increases the risk of reproductive impairment upon hCG treatment.

ABSTRACT

Endocrine disrupting chemicals (EDCs), like bisphenol A (BPA) and benzophenone-3 (BP-3), can interfere with
hormone systems, posing risks to fertility and reproduction. Exposure to EDCs is unavoidable making it a relevant
environmental health topic, however the impact of real-life EDC mixtures is largely unknown. This study
explored the effects of a combined BPA and BP-3 exposure at tolerable intake levels for humans during pregnancy
and early life on ovarian development and function in an established mouse model. Mice were daily exposed to
concentrations of 4 µg/kg BPA orally, 50 mg/kg BP-3 dermally, and the combination of BPA+BP-3 through
gestation and lactation, a susceptible developmental period. Female offspring of BPA and BP-3 exposed mice
exhibited increased birth weight and elevated bodyweight by postnatal day 7. By day 30, after hormonal
stimulation to induce ovulation, exposed offspring showed disrupted ovarian follicle maturation and altered
ovarian response to stimulation with exogenous gonadotropins. Moreover, the number of NK cells rose in the
ovaries, and genes linked to hormone signaling, hormone synthesis, and ovarian tissue remodeling were altered
relative to unexposed controls.

These findings suggest that early life exposure to BPA and BP-3 at environmentally relevant doses impairs ovarian development and function in mice indicating that immune cells and
hormonal signaling in the ovaries are targets of endocrine disruptors at relevant concentrations. Such endocrine
disruption may be compromising fertility and reproductive health in later life. Our research underscores the
importance of investigating the impact of combined EDC exposure on the reproductive system.

Article

These findings suggest that early life exposure to BPA and BP-3 at environmentally relevant doses impairs ovarian development and function in mice indicating that immune cells and
hormonal signaling in the ovaries are targets of endocrine disruptors at relevant concentrations. Such endocrine
disruption may be compromising fertility and reproductive health in later life.

This study explored the effects of a combined BPA and BP-3 exposure at tolerable intake levels for humans during pregnancy and early life on ovarian development and function in an established mouse model.

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