Prenatal testosterone transfer

Prenatal Testosterone Transfer (also known as prenatal androgen transfer or prenatal hormone transfer) refers to the phenomenon in which testosterone synthesized by a developing male fetus transfers to one or more developing fetuses within the womb and influences development. This typically results in the partial masculinization of specific aspects of female behavior, cognition, and morphology,[1] though some studies have found that testosterone transfer can cause an exaggerated masculinization in males.[2] There is strong evidence supporting the occurrence of prenatal testosterone transfer in rodents and other litter-bearing species,[1] such as pigs.[3] When it comes to humans, studies comparing dizygotic opposite-sex and same-sex twins suggest the phenomenon may occur, though the results of these studies are often inconsistent.[4][5]

Mechanisms of transfer

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Testosterone is a steroid hormone; therefore it has the ability to diffuse through the amniotic fluid between fetuses.[6] In addition, hormones can transfer among fetuses through the mother's bloodstream.[7]

Consequences of testosterone transfer

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During prenatal development, testosterone exposure is directly responsible for masculinizing the genitals[8] and brain structures.[9] This exposure leads to an increase in male-typical behavior.[10]

Animal studies

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Most animal studies are performed on rats or mice. In these studies, the amount of testosterone each individual fetus is exposed to depends on its intrauterine position (IUP). Each gestating fetus not at either end of the uterine horn is surrounded by either two males (2M), two females (0M), or one female and one male (1M). Development of the fetus varies widely according to its IUP.[1]

Mice

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In mice, prenatal testosterone transfer causes higher blood concentrations of testosterone in 2M females when compared to 1M or 0M females.[6] This has a variety of consequences on later female behavior, physiology, and morphology.

Below is a table comparing physiological, morphological, and behavioral differences of 0M and 2M female mice.[1]

0M Female Mice 2M Female Mice
Physiology Lower fetal testosterone levels[11] Higher fetal testosterone levels[6]
Earlier vaginal opening[12] Later vaginal opening[13]
Less male offspring[14] More male offspring[14]
Mate and impregnated earlier[13] Mate and impregnated later[13]
Less sensitive to testosterone[15] More sensitive to testosterone[16]
Morphology Shorter anogenital distance[15] Longer anogenital distance[11]
Behavior Less likely to mount other females[17] More likely to mount other females[18]
Less aggressive[15] More aggressive[11]

Human studies

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Studies involving humans often compare opposite-sex to same-sex dizygotic twins. Females of opposite-sex twin pairs are thought to have partially masculinized traits as a result of gestating along with a male. These studies test for a range of masculinized cognitive, morphological, physiological, and behavioral traits. Studies testing for differences in behavior (i.e. temperament) tend to yield inconsistent results,[19] while those testing perception and cognition are typically more consistent.[5] Though supporting evidence exists, whether or not prenatal testosterone transfer occurs in humans remains debatable.

Listed below are different types of opposite-sex versus same-sex twin tests used to determine whether prenatal testosterone transfer occurs in humans.

Tests of Behavior

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Tests of Perception and Cognition

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Tests of Physiology and Morphology

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References

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  1. ^ a b c d Ryan, B.C.; Vandenbergh, J.G. (2002). "Intrauterine position effects". Neuroscience & Biobehavioral Reviews. 26 (6): 665–678. doi:10.1016/S0149-7634(02)00038-6. PMID 12479841. S2CID 27722357.
  2. ^ Clark, M.M.; Tucker, L.; Galfed, J.B.G. (1992). "Stud males and dud males: intrauterine position effects on the reproductive success of male gerbils". Animal Behaviour. 43 (2): 215–221. doi:10.1016/S0003-3472(05)80217-9. S2CID 17651606.
  3. ^ Rohde Parfet KA, Lamberson WR, Rieke AR, Cantley TC, Ganjam VK, vom Saal FS, Day BN (1990). "Intrauterine position effects in male and female swine: Subsequent survivability, growth rate, morphology, and semen characteristics". Journal of Animal Science. 68 (1): 179–185. doi:10.2527/1990.681179x. PMID 2303395.
  4. ^ a b c Cohen-Bendahan CC, Buitelaar JK, van Goozen SH, Orlebeke JF, Cohen-Kettenis PT (2005a). "Is there an effect of prenatal testosterone on aggression and other behavioral traits? A study comparing same-sex and opposite-sex twin girls". Hormones and Behavior. 47 (2): 230–237. doi:10.1016/j.yhbeh.2004.10.006. PMID 15664027. S2CID 25095661.
  5. ^ a b Tapp, A.L.; Mayberry, M.T.; Whitehouse, A.J.O. (2011). "Evaluating the twin testosterone transfer hypothesis: A review of the empirical evidence". Hormones and Behavior. 60 (5): 713–722. doi:10.1016/j.yhbeh.2011.08.011. PMID 21893061. S2CID 2776478.
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  7. ^ Gorodeski, G.I.; Sheean, L.A.; Utian, W.H. (1995). "Sex hormone modulation of flow velocity in the parametrial artery of the pregnant rat". Am. J. Physiol. 268 (3 Pt 2): R614–R624. doi:10.1152/ajpregu.1995.268.3.R614. PMID 7900903.
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  14. ^ a b Vandenbergh, J.G.; Huggett, C.L. (1995). "The anogenital distance index, a predictor of the intrauterine position effects on reproduction in female house mice". Lab. Anim. Sci. 45 (5): 567–573. PMID 8569159.
  15. ^ a b c Gandelman R, vom Saal FS, Reinisch JM (1977). "Contiguity to male fetuses affects morphology and behaviour of female mice". Nature. 266 (5604): 722–724. Bibcode:1977Natur.266..722G. doi:10.1038/266722a0. PMID 559940. S2CID 4150169.
  16. ^ vom Saal, F.S.; Grant, W.M.; McMullen, C.W.; Laves, K.S. (1983). "High fetal estrogen concentrations: correlation with increased adult sexual activity and decreased aggression in male mice". Science. 220 (4603): 1306–1309. Bibcode:1983Sci...220.1306V. doi:10.1126/science.6857252. PMID 6857252.
  17. ^ Quadagno, D.M.; McQuitty, C.; McKee, J.; Koelliker, L.; Wolfe, G.; Johnson, D.C. (1987). "The effects of intrauterine position on competition and behavior in the mouse". Physiol. Behav. 41 (6): 639–642. doi:10.1016/0031-9384(87)90323-4. PMID 3441535. S2CID 46203626.
  18. ^ Rines JP, vom Saal FS (1984). "Fetal effects on sexual behavior and aggression in young and old female mice treated with estrogen and testosterone". Hormones and Behavior. 18 (2): 117–129. doi:10.1016/0018-506X(84)90037-0. PMID 6539747. S2CID 37946760.
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