Prenatal letrozole produces a subpopulation of male rats with same-sex preference and arousal as well as female sexual behavior

Olvera-Hernández, Sandra; Chavira, Roberto; Fernández‐Guasti, Alonso

doi:10.1016/j.physbeh.2014.11.060

Cited by 30 publications

(12 citation statements)

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“…XY-chromosome individuals with complete androgen insensitivity syndrome (CAIS) show fewer male-typical behaviors and more female-typical behaviors despite normally functioning testes with androgen exposure during gestation[ 7 , 8 ]. These findings have been supported by studies using animals[ 9 – 11 ], which revealed that experimental manipulations of hormones during gestation affected the sexual dimorphism of behaviors.…”

Section: Introductionmentioning

confidence: 68%

The Relationship between the Second-to-Fourth Digit Ratio and Behavioral Sexual Dimorphism in School-Aged Children

et al. 2016

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Sexually dimorphic brain development and behavior are known to be influenced by sex hormones exposure in prenatal periods. On the other hand, second-to forth digit ratio (2D/4D) has been used as an indirect method to investigate the putative effects of prenatal exposure to androgen. In the present study, we herein investigated the relationship between gender-role play behavior and the second-to-fourth digit ratio (2D/4D), which has been used as an indirect method to investigate the putative effects of prenatal exposure to androgens, in school-aged children. Among 4981 children who became 8 years old by November 2014 and were contactable for this survey by The Hokkaido Study of Environment and Children's Health, 1631 (32.7%), who had data for 2D/4D and Pre-school Activities Inventory (PSAI) as well as data for the survey at baseline, were available for analysis. Parents sent reports of PSAI on the sex-typical characteristics, preferred toys, and play activities of children, and black and white photocopies of the left and right hand palms via mail. PSAI consisted of 12 masculine items and 12 feminine items, and a composite score was created by subtracting the feminine score from the masculine score, with higher scores representing masculine-typical behavior. While composite scores in PSAI were significantly higher in boys than in girls, 2D/4D was significantly lower in boys than in girls. Although the presence or absence of brothers or sisters affected the composite, masculine, and feminine scored of PSAI, a multivariate regression model revealed that 2D/4D negatively correlated with the composite scores of PSAI in boys, whereas no correlation was found in girls. Although 2D/4D negatively correlated with the masculine score in boys and girls, no correlation was observed between 2D/4D and the feminine score. In conclusion, although social factors, such as the existence of brother or sisters, affect dimorphic brain development and behavior in childhood, the present study revealed that the prenatal hormonal environment was an important factor influencing masculine-typical dimorphic brain development and behavior in school-aged children.

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Section: Introductionmentioning

confidence: 68%

The Relationship between the Second-to-Fourth Digit Ratio and Behavioral Sexual Dimorphism in School-Aged Children

et al. 2016

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“…This effect could be associated with the uterine blood flow, since blood flows predominantly from the cervix to the ovaries in pregnant rats (Lipton et al, 1998). In the same context, a recent paper showed that prenatal exposure to letrozole produces two subpopulations of rats with different sex preference (Olvera-Hernández, Chvira & Fernández-Guasti, 2015). To explain this observation, the authors suggested that the fetuses were exposed in utero to a different amount of drug.…”

Section: Discussionmentioning

confidence: 99%

Pentylenetetrazole-induced seizures in developing rats prenatally exposed to valproic acid

Puig-Lagunes

Manzo

Beltran-Parrazal

et al. 2016

PeerJ

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BackgroundEpidemiological evidence indicates epilepsy is more common in patients with autism spectrum disorders (ASD) (20–25%) than in the general population. The aim of this project was to analyze seizure susceptibility in developing rats prenatally exposed to valproic acid (VPA) as autism model.MethodsPregnant females were injected with VPA during the twelfth embryonic day. Seizures were induced in fourteen-days-old rat pups using two models of convulsions: pentylenetetrazole (PTZ) and lithium-pilocarpine (Li-Pilo).ResultsTwo subgroups with different PTZ-induced seizure susceptibility in rats exposed to VPA were found: a high susceptibility (VPA+) (28/42, seizure severity 5) and a low susceptibility (VPA−) (14/42, seizure severity 2). The VPA+ subgroup exhibited an increased duration of the generalized tonic-clonic seizure (GTCS; 45 ± 2.7 min), a higher number of rats showed several GTCS (14/28) and developed status epilepticus (SE) after PTZ injection (19/27) compared with control animals (36.6 ± 1.9 min; 10/39; 15/39, respectively). No differences in seizure severity, latency or duration of SE induced by Li-Pilo were detected between VPA and control animals.DiscussionPrenatal VPA modifies the susceptibility to PTZ-induced seizures in developing rats, which may be linked to an alteration in the GABAergic transmission. These findings contribute to a better understanding of the comorbidity between autism and epilepsy.

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“…Pharmacological manipulation of aromatase has also been utilized to examine the effects of the removal of E2 during gestation on later adult sexual behaviors. Olvera-Hernandez et al (2015) reported a feminized-pattern of results in male Wistar rats after prenatal exposure to Letrozole (0.56 μg/kg of the dam) with 30% of males showing same-sex preference and 33% displaying lordosis. However, 44% of treated males also displayed a completely masculinized pattern of sexual behavior, i.e., mounting behaviors, intromission, and ejaculation toward receptive females ( Olvera-Hernandez et al, 2015 ), suggestive that some males might be resistant to the effects of this AI.…”

Section: Aromatase and Sociosexual Behaviorsmentioning

confidence: 99%

“… Olvera-Hernandez et al (2015) reported a feminized-pattern of results in male Wistar rats after prenatal exposure to Letrozole (0.56 μg/kg of the dam) with 30% of males showing same-sex preference and 33% displaying lordosis. However, 44% of treated males also displayed a completely masculinized pattern of sexual behavior, i.e., mounting behaviors, intromission, and ejaculation toward receptive females ( Olvera-Hernandez et al, 2015 ), suggestive that some males might be resistant to the effects of this AI. The mechanism by which prenatal exposure to AI affects adult sexual behavior could be epigenetic in origin ( Matsuda et al, 2011 ; Nugent et al, 2015 ; McCarthy et al, 2017 ).…”

Section: Aromatase and Sociosexual Behaviorsmentioning

confidence: 99%

Sexually Dimorphic Effects of Aromatase on Neurobehavioral Responses

Shay

Vieira‐Potter

Rosenfeld

2018

Front. Mol. Neurosci.

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Aromatase is the enzyme responsible for converting testosterone to estradiol. In mammals, aromatase is expressed in the testes, ovaries, brain, and other tissues. While estrogen is traditionally associated with reproduction and sexual behavior in females, our current understanding broadens this perspective to include such biological functions as metabolism and cognition. It is now well-recognized that aromatase plays a vital lifetime role in brain development and neurobehavioral function in both sexes. Thus, ongoing investigations seek to highlight potentially vital sex differences in the role of aromatase, particularly regarding its centrally mediated effects. To characterize the role of aromatase in mediating such functions, effects of aromatase inhibitor (AI) treatments on humans and animal models have been determined. Aromatase knockout (ArKO) mice that systemically lack the enzyme have also been employed. Humans possessing mutations in the gene encoding aromatase, CYP19, have also provided critical insight into how aromatase affects brain function in a possible sex-dependent manner. A better understanding of how AIs, used to treat breast cancer and other clinical conditions, may detrimentally affect neurobehavioral responses will likely promote development of future therapies to combat these effects. Herein, we will provide a critical review of the current knowledge of sex differences in aromatase regulation of various neurobehavioral functions. Although many species have been used to better understand the functions of aromatase, this review focuses on rodent models and humans. Critical gaps in our present understanding of this area will be considered, and important future research directions will be discussed.

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Prenatal letrozole produces a subpopulation of male rats with same-sex preference and arousal as well as female sexual behavior

Cited by 30 publications

References 71 publications

The Relationship between the Second-to-Fourth Digit Ratio and Behavioral Sexual Dimorphism in School-Aged Children

The Relationship between the Second-to-Fourth Digit Ratio and Behavioral Sexual Dimorphism in School-Aged Children

Pentylenetetrazole-induced seizures in developing rats prenatally exposed to valproic acid

Sexually Dimorphic Effects of Aromatase on Neurobehavioral Responses

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