Prenatal Testosterone Exposure Effects on Female Sexual Behavior in High and Low Licking/Grooming Offspring

Amanda P. Borrow, Nicole M. Cameron Psychology Department, SUNY Binghamton, Binghamton NY, USA, 13902

Introduction In girls, onset of puberty and sexual promiscuity are influenced by mother-child interaction (Belsky et al. 2010). Onset of puberty is also affected by steroid exposure during development (Mouritsen et al. 2010). In female rats, the influence of maternal care is also important. Greater maternal care levels decrease female offspring’s receptivity towards males and motivation to mate (Cameron et al. 2008). Cross fostering is not sufficient to reverse the phenotype of Low but not of females born to High licking/grooming (LG) mothers (Cameron et al. 2008). In utero testosterone exposure is also associated with High LG and may play a role in onset of puberty and sexual behavior.

Hypothesis

In utero testosterone exposure will inhibit the effects of low maternal care levels on female offspring’s behavior and physiology.

Methods

Mother’s LG scores (Fig 1) were determined by observing the first 6 days postpartum five times a day for 72 minutes.

Fig.1 Frequency of % LG scores Dams were implanted with a 5mg-21 day slow release testosterone pellet (T) or a placebo (P) (Innovative Research of America) on day 16 of pregnancy (Placebo, M=97.81±15.91 pg/ml; Testosterone, M=1927.38±423.17 pg/ml). Anogenital distance was measured at Day 55. Adult female offspring were ovariectomized and steroid-primed or sham-operated and mated in a pacing-chamber for 45 min or 15 intromissions. Sexual behaviors were recorded and scored. Sham-operated female’s brains were collected following perfusion 90 min after mating. For estrogen receptor alpha visualization via immunohistochemistry, sections were placed in rabbit anti-ER alpha (1:30,000; sc-542; Santa Cruz, CA).Every fifth section of the anteroventral periventricular nucleus (AVPV), the medial preoptic area (mPOA) and the ventromedial hypothalamus (VMH) were analyzed.

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Fig. 2. Testosterone increased anogenital index (AGI) for both Low (p<0.01) and High (p<0.01) females.

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Phenotype Treatment Surgery n Mounts Intromissions Ejacula8ons Percent  Exits

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Placebo  

   

Testosteron

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OVX  

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OVX

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28.80±9.09  

15.00±7.64  

31.11±7.38  

34.50±8.20

11.00±1.22  

6.50±1.71  

8.11±1.77  

8.38±1.88

1.20±0.20a  

0.83±0.31ab  

0.33±0.17ab  

0.50±0.19ab

44.15±14.84a  

70.49±5.34b  

58.32±6.83ab  

47.85±7.23ab

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Placebo  

   

Testosteron

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Sham  

OVX  

Sham  

OVX

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7  

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23.60±9.813

0.29±11.33  

20.80±7.32  

17.43±4.33

5.20±2.27  

5.00±2.42  

6.20±2.48  

9.14±2.14

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0.43±0.21ab

45.94±9.85ab  

57.18±6.98ab  

68.01±8.19ab  

44.53±9.11a Table 1. Sexual behavior received and percent exits from the center chamber following male behavior for Low, Mid, and High LG females exposed to T or P pellets and OVX or sham-operated in adulthood. *p<0.05

Fig. 3. Surgery significantly decreased average lordosis rating (p<0.05). An interaction between maternal care, testosterone treatment, and steroid replacement was found (p<0.05).

Fig. 4. An LG phenotype x Treatment interaction was seen for the rate of paracopulatory behavior (p<0.05).

Fig. 5. Testosterone significantly decreased ER alpha-ir in the AVPV (a), but not in the mPOA (b) or the VMH (c). (d) AVPV of control-treated animal (left) and testosterone-treated animal (right) (e) mPOA of control-treated animal (left) and testosterone-treated animal (right) (f) VMH of control-treated animal (left) and testosterone-treated animal (right)

(a) (b) (c) 4.1-5.0 6.1-7.0 8.1-9 10.1-11 12.1-13 14.1-15 16.1-17

% Licking & Grooming

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*  

*  

Summary •  Testosterone caused masculinization of female

genitalia. •  Testosterone inhibits the effects of maternal care on

lordosis rating, the rate of paracopulatory behavior and the number of ejaculations received.

•  Circulating endogenous hormone levels particularly influence High LG offspring sexual behavior

•  Testosterone decreased estrogen receptor alpha expression in the AVPV, but not the mPOA or VMH

Conclusion Testosterone succeeded in inhibiting lower maternal care level effects on sexual behavior. These findings demonstrate that greater testosterone in utero exposure in Highs may be in part responsible for lowered sexual proceptivity and receptivity.

Future Experiments Assessing the effects of prenatal exposure to aromatase inhibitor and androgen receptor inhibitor on sexual behavior and estrogen receptor alpha expression in adult females of High and Low LG animals.

References Belsky et al. (2010) Develop Psychol, 46:120-8 Cameron et al. (2008) PLoS ONE, e2210 Mouritsen et al. (2010) Int J Androl, 33:346-59 http://www.flickr.com/photos/necilbug/3357394357

(d) (e) (f)

Control Control Control Testosterone Testosterone Testosterone

AVPV mPOA VMH