Prenatal testosterone propionate and postnatal ovarian activity in the rat

Abstract

Testosterone propionate (TP) was given to rats on days 16 through 20 of pregnancy (2 mg/day). Female young had masculinized external genitalia. Sexual maturity was accelerated in TP females, despite lower weights and shorter lengths of body and tail. Placental and body weights were lower in TP females and males than in controls. The inhibiting effect of TP on postnatal growth is probably mediated by its effect on birth weight through placental damage. Ovarian cyclicity occurred upon reaching sexual maturity. In one experiment TP females were ovariectomized at 6 weeks, and given ovarian and vaginal grafts. Most of these animals showed regular cyclicity in vaginal smears between 74\p=m-\100 days. Thus neither the 'early', nor the 'delayed early androgen syndrome' occurred in these experiments.This absence of effect of prenatal TP on ovarian cyclicity is attributable to a placental barrier for testosterone. When maternal plasma testosterone was raised 20-fold by exogenous TP, foetal testosterone levels remained unchanged. More detailed information was obtained when labelled testosterone was infused into a pregnant rat.

Plasma testosterone in fetal rats and their mothers on day 19 of gestation

“…While there remains some question regarding the extent to which maternal testosterone can impact behavioral masculinization of female fetuses (16,22), it is commonly accepted that systemic testosterone administration to pregnant females results in behavioral masculinization of female offspring (e.g., 9,34), presumably through the transfer of androgens from maternal blood to fetal circulation.…”

Role of androgens in normal and pathological ovarian function

“…Both prenatal aromatisable (testosterone) and non-aromatisable (DHT) androgen exposure abolished an E 2 benzoate-induced LH surge, implying that direct prenatal AR activation is involved in altering the GnRH/LH neurosecretory system (Foecking et al 2005). On the other hand, in other studies, late gestational treatment of mice with testosterone (Keisler et al 1991) or rats with TP (Swanson & Werff ten Bosch 1964, Fels & Bosch 1971, Huffman & Hendricks 1981, Slob et al 1983, Tyndall et al 2012) had no effect on cyclicity or ovarian function, inferred by the presence of follicles at various stages and CL. Variations in the observed phenotypes induced by prenatal treatment with testosterone or TP may be due to the degree of transplacental transfer of the administered steroid into the foetus (Fels & Bosch 1971).…”

Maternal androgen excess reduces placental and fetal weights, increases placental steroidogenesis, and leads to long-term health effects in their female offspring

“…However, because testosterone is lipophilic, it may diffuse across the placenta and exert direct effects on fetal growth and/or energy homeostasis (28). Alternatively, testosterone may affect placental development and function by modulating amino acid transporters (35,42) or by regulating the expression of enzymes and/or androgen/ estrogen receptors, as demonstrated in human placentas in pregnancies complicated by preeclampsia (21, 34). Whether placental steroidogenesis is dysregulated due to excess prenatal Address for reprint requests and other correspondence: E. Stener-Victorin, Institute of Neuroscience and Physiology,…”