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Excess Androgens in Utero Alters Fetal Testis Development.

Connolly, Fiona; Rae, Mick T; Bittner, Lilli; Hogg, Kirsten; McNeilly, Alan S; Duncan, W Colin


Fiona Connolly

Lilli Bittner

Kirsten Hogg

Alan S McNeilly

W Colin Duncan


Prenatal androgenization induces a polycystic ovary syndrome-like phenotype in adult female offspring, which is associated with alterations that can be detected in the fetal ovary, suggesting gestational origins of this condition. We therefore investigated whether increased prenatal androgen exposure also altered testicular development using ovine animal models. Biweekly maternal testosterone propionate (TP; 100 mg) from day 62 to day 70/day 90 of gestation altered male developmental trajectory. In male fetuses serum LH was decreased (P < .01), and testicular STAR, CYP11, and CYP17 abundance were reduced. Coincident with this, basal testicular T synthesis was decreased in vitro (P < .001). Leydig cell distribution was severely perturbed in all testes prenatally exposed to TP (P < .001). To examine the contribution of estrogens, fetuses were injected with TP (20 mg), the potent estrogen agonist, diethylstilbestrol (DES; 20 mg), or vehicle control at day 62 and day 82 and assessed at day 90. The effects of fetal (direct) TP treatment, but not DES, paralleled maternal (indirect) TP exposure, supporting a direct androgen effect. Cessation of maternal androgenization at day 102 returned Leydig cell distribution to normal but increased basal T output, at day 112, demonstrating Leydig cell developmental plasticity. Earlier maternal androgen exposure from day 30 similarly influenced Leydig cell development at day 90 but additionally affected the expression of Sertoli and germ cell markers. We show in this study that increased prenatal androgen exposure alters development and function of Leydig cells at a time when androgen production is paramount for male development. This supports the concept that gestational antecedents associated with polycystic ovary syndrome may have effects on the male fetus.


Connolly, F., Rae, M. T., Bittner, L., Hogg, K., McNeilly, A. S., & Duncan, W. C. (2013). Excess Androgens in Utero Alters Fetal Testis Development. Endocrinology, 154, 1921-1933.

Journal Article Type Article
Publication Date 2013
Deposit Date Mar 27, 2014
Print ISSN 0013-7227
Electronic ISSN 1945-7170
Publisher Endocrine Society
Peer Reviewed Peer Reviewed
Volume 154
Pages 1921-1933
Keywords Prenatal androgenization; polycystic ovary syndrome-like phenotype; Leydig cells;
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