Female sexual behavior, estrous cycle and gene expression in sexually dimorphic brain regions after pre- and postnatal exposure to endocrine active UV filters.
The developing female brain represents a potential target for estrogenic environmental chemicals because it depends on estrogen but is exposed to low endogenous estrogen levels, thus facilitating competition by exogenous estrogen receptor (ER) agonists. We investigated effects of two estrogenic UV filters, 4-methylbenzylidene camphor (4-MBC) and 3-benzylidene camphor (3-BC). 4-MBC has been detected in human milk, indicating potential exposure of fetus and infant. The two chemicals were administered in chow to rats of the parent generation before mating, during pregnancy and lactation, and to their offspring until adulthood. Female sexual behavior was recorded on videotape in adult female offspring on proestrus evening at the beginning of the dark phase. 4-MBC (7 and 24mg/kg bw/day) and 3-BC (2.4 and 7mg/kg bw/day) reduced proceptive behavior (jump and ear wiggling) and receptive behavior (lordosis quotient), and increased rejection behavior towards the male. Estrous cycles were not affected by 4-MBC but disturbed by 3-BC. mRNAs encoding for genes involved in female sexual behavior, ERalpha, ERbeta, progesterone receptor (PR) and steroid receptor coactivator-1 (SRC-1), were measured by real-time RT-PCR in ventromedial hypothalamic nucleus (VMH) and medial preoptic area of adult male and female offspring (studied in diestrus) after pre- and postnatal exposure to 3-BC (0.24, 0.7, 2.4 and 7mg/kg bw/day). Gene expression was affected in a sex- and region-specific manner. PR mRNA in female VMH was reduced to male levels at dose levels of 2.4 and 7mg/kg bw/day 3-BC. Our data demonstrate that female sexual behavior represents a sensitive target of endocrine disrupters and point to an involvement of PR in VMH.
Faass
Oliver
O
GREEN Tox and Institute of Anatomy, University of Zurich, Zurich, Switzerland.
Schlumpf
Margret
M
Reolon
Sasha
S
Henseler
Manuel
M
Maerkel
Kirsten
K
Durrer
Stefan
S
Lichtensteiger
Walter
W
D000818:Animals; D000831:Animals, Newborn; D001593:Benzyl Compounds / Q000008:administration & dosage; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002164:Camphor / Q000008:administration & dosage / Q000031:analogs & derivatives; D004703:Endocrine System / Q000187:drug effects* / Q000378:metabolism; D030762:Estrous Cycle / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012727:Sex Characteristics; D012737:Sex Factors; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D013473:Sunscreening Agents / Q000008:administration & dosage*; D014466:Ultraviolet Rays
D001593:Benzyl Compounds; D013473:Sunscreening Agents; C511303:3-benzylidene camphor; D002164:Camphor; C038939:enzacamene