Environmental Estrogen Chlordecone Study On The Influence Of Female Mandarin Vole Sexual Orientation And Brain Estrogen Alpha Receptor

Steriod hormones levels in early development may play an important role in the adult rodents'sexual partner preference.Sexual partner preference is sexual dimorphic,while females prefer males and males prefer females.Many experimental studies indicate that abnormal steriod hormones levels in perinatal period(at the end of gestation and shortly after birth) may affect sexual dimorphisms in brain and behavior during development,which induce abnormal sexual orientation and social behavior in adulthood.The paradigm of this step in the sexual differentiation process of mammals is that:in the presence of high concentration estrogen a male brain differentiation follows, while in the absense of estrogen(as is the normal situation in females) a female brain differentiation follows.The function of estrogen is induced by estrogen receptor alpha(ERα) and estrogen receptor beta(ERβ),ERαprimarly involved in masculinization,while ERβplays a major role in defeninization of sexual orientation and sexual behavior.The chlorinated pesticide chlordecone(CD) is a relatively strong estrogenic chemical and CD acts as a competitive agonist for ERα.CD is associated with estrogenic effects in humans following cases of reproductive dysfunction and neurotoxicity in men exposed in an occupational incident. Female rats exposed in utero to CD showed an increased male mounting as compared to female control rats,but whether the adults' sexual orientation,social interaction and ERαexpression in the brain can be changed when treated with high dose CD or estrogen during early development is not very clear.Then,we investigated the effect of neonatal exposure to CD or estrogen on sexual orientation,social interaction and ERαexpression,so as to study the mechanism of homosexual in reproduction and social behavior.Mandarin vole(Microtus mandaritus),which are high socially monogamous rodent,has become important animal mode of sexual behavioral nurobiology.Immediately after birth,female pups received a single high dose of CD or estrogen,then sexual partner preference was tested to validate whether neonatal exposure to CD can affect the sexual partner preference like estrogen.Then the mandarin voles' social interaction,sexual partner preference and ERαdistribution were tested so as to study the effects of neonatal exposure to CD and estrogen in females and investigate the mechanism of sexual orientation and sexual preference. Our results were the following:1.Results of social interaction of CD group:Mandarin voles of CD group expressed significantly less aggression and more affiliation compared with control females(P＜0.01),it reveals that CD group shows more prosocial behavior and enhances the social connection between each other.When compared with control males,CD group showed more defensive behavior(P＜0.05),but there is no differences in other social behaviors between two groups.It is suggest that the behaviors of CD group were masculinized,then they can express the male-like social behavior in adulthood.2.Results of social interaction of E2 group:Mandarin voles of E2 group showed less aggression and more affiliation compared with control females(P＜0.05),additionally,E2 group expressed the mounting behavior,it revesls that estrogen masculinized the E2 group's sexual behavior.When compared with control males,E2 group mandarin voles expressed more denfensive behavior and less affiliation(P＜0.05).These show that females' social behaviors were masculined but there is still difference with control males'.Additionally,there is no significant difference between CD group and E2 group in their social behaviors to the same sex when tested in social interaction.These reveal that CD and E2 may act the same effect on masculinization of the females' social behaviors.3.Results of sexual orientation of CD group:Mandarin voles of CD group showed a sexual orientation to female and spent more time with female mandarin voles compared with control females(P＜0.05).There is no significant difference in the time of visiting male or female mandarin vole between CD group and control males and the preference score reveals the same case.These results indicate that CD group mandarin voles' sexual orientation has been changed when treated with high dose of CD in 24h after birth and prefer the females to males in adulthood.4.Results of sexual orientation of E2 group;E2 group spent less time with males compared with control females(P＜0.05);There is no significant difference in the time of visiting male or female mandarin vole between E2 group and control males.The preference score reveals that E2 group prefers females to males and has no significant difference with control males.Additionally,there is no significant difference between CD group and E2 group in the time of visiting male or female and the preference scores.It reveals that CD and E2 act the same effects on the masculinization of the females' sexual orientation.5.Results of sexual partner preference of CD group and E2 group:CD group and E2 group mandarin voles showed more frequences of affiliation and mounting to stimulus female than control females(P＜0.05);CD group and E2 group expressed less time of aggression to stimulus female compared with control females(P＜0.05);CD group spent more time of affiliation,mounting and investigation on stimulus female than control females(P＜0.05),and there is no significant difference in the aggression,affiliation,mounting and investigation on stimulus female between CD group and E2 group.These results indicate that treated with high dose of CD or E2 in 24h after birth can masculinize females' social behaviors and show more prosocial behavior with female,even can mount onto females in adulthood.CD group and E2 group showed less frequences and less total duration of lordosis,affiliation and investigation on stimulus male than control females(P＜0.05),and E2 group expressed less frequences and less total duration of affilitaion and mounting than CD group(P＜0.05).These data reveal that esposure to high dose of CD or E2 in 24h after birth,females' social behavior and sexual behavior can be defeminized and masculinized.CD group and E2 group expressed less total duration of affiliative behavior to stimulus than control males(P＜0.05),but no significant difference in any social behavior frequences compared with control males;There is no significant difference in the social behaviors to stimulus male between CD group and E2 group.E2 group showed less frequence of aggression to stimulus male than control males(P＜0.05), and expressed less frequence of mounting on stimulus male compared with CD group and control males(P＜0.05);CD group showed more frequence of lordosis to stimulus male compared with E2 group and control males(P＜0.05);CD group and E2 group spent more time on defensing stimulus males than control males(P＜0.05);E2 group had less total duration of affiliation and mounting than CD group and control males(P＜0.05).These results show that exposure to high dose of CD or E2 in 24h after birth,females expressed more male-typical social behaviors,including sexual behavior in adulthood.6.Results of ERαdistribution in four groups:In comparison to control females,CD group mandarin voles expressed less ERαin the arcuate hypothalamic nucleus(AR)(P＜0.05),the bed nucleus of the stria terminalis(BST)(P＜0.01),Central amygdaloid nucleus(Ce)(P＜0.01),Medial amygdaloid nucleus(MeA)(P＜0.01),the ventromedial hypothalamic nucleus(VMH)(P＜0.01) but more ERαin the media prioptic area(MPO)(P＜0.01).When compared with control males,CD group mandarin voles expressed less ERαin the AR(P＜0.01),MeA(P＜0.05),VMH(P＜0.01) but more ERαin the BST(P＜0.05) and MPO(P＜0.01).These results indicate that exposure to high dose of CD in 24h after birth,the distribution of ERαin female mandarin voles' brains has been changed and like the mode of control males.When compared with the E2 group,CD group mandarin voles expressed less ERαin the AR(P＜0.01),the VMH(P＜0.01) but more ERαin the MPO(P＜0.01);There is no significant differerce in the BST,MeA and Ce between two groups.It reveals that CD group and E2 group have the same case in ERαdistribution in the brain areas which regulate social behaviors and emotion.In conclusion,These results indicate that neonatal exposure to high dose of CD or E2 can alter adult female rodents' social behaviors and sexual orientation,and express male-typical behavior pattern in social interaction and sexual partner preference.It can also alter the ERαdistribution pattern in female's brain areas which regulate the social behaviors and sexual behavior.These results may be are important to reveal the mechanism underlying abnormal sexual behavior and orientation.