First ovarian response to gonadotrophin stimulation in rats exposed to neonatal androgen excess
This study analyzes the effects of neonatal androgenization on follicular growth and first ovulation in response to gonadotrophins, using a model of exogenous stimulation or the use of subcutaneous ovary grafts in castrated animals to replace the hypothalamus–pituitary signal. Neonatal rats (days 1–5) were treated with testosterone, dihydrotestosterone or vehicle. At juvenile period, rats were stimulated with PMSG, hCG (alone or combined) or used as ovarian donors to be grafted on castrated adult female rats. Ovulation and ovarian histology were analyzed in both groups. Animals treated with vehicle or dihydrotestosterone stimulated with gonadotrophins (pharmacological or by using an ovary graft) ovulated, showing a normal histological morphology whereas rats exposed to testosterone and injected with the same doses of gonadotrophins did not it. In this group, ovulation was reached using a higher dose of hCG. Ovaries in the testosterone group were characterized by the presence of follicles with atretic appearance and a larger size than those observed in control or dihydrotestosterone groups. A similar appearance was observed in testosterone ovary grafts although luteinization and some corpora lutea were also identified. Our findings suggest that neonatal exposure to aromatizable androgens induces a more drastic signalling on the ovarian tissue that those driven by non-aromatizable androgens in response to gonadotrophins.
KeywordsTestosterone Dihydrotestosterone Follicle Ovulation Graft hCG
We gratefully acknowledge to Karina Hernandez for histotechnical assistance and Mariela Santos for animal care support.
This work was partially supported by the PEDECIBA, Universidad de la República, Montevideo, Uruguay.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Abbott DH, Dumesic DA, Levine JE et al (2006) Animal models and fetal programming of the polycystic ovary syndrome. In: Azziz R, Nestler JE, Dewailly D (eds) Androgen excess disorders in women. Humana Press, Totowa, pp 259–272Google Scholar
- Dutta S, Mark-Kappeler CJ, Hoyer PB, Pepling ME (2014) The steroid hormone environment during primordial follicle formation in perinatal mouse ovaries. Biol Reprod 91(68):1–12Google Scholar
- Sotomayor-Zárate R, Tiszavari M, Cruz G, Lara HE (2011) Neonatal exposure to single doses of estradiol or testosterone programs ovarian follicular development-modified hypothalamic neurotransmitters and causes polycystic ovary during adulthood in the rat. Fertil Steril 96:1490–1496CrossRefGoogle Scholar