Polycystic ovary syndrome induced by exposure to testosterone propionate and effects of sympathectomy on the persistence of the syndrome

Leticia Morales-Ledesma,Juan Antonio Díaz Ramos,Angélica Trujillo Hernández

doi:10.1186/s12958-017-0267-0

Leticia Morales-Ledesma, Juan Antonio Díaz Ramos + Show 1 more

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https://doi.org/10.1186/s12958-017-0267-0

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Abstract

Polycystic ovary syndrome is a complex disorder affecting 6 to 10% of women of reproductive age. In recent years, the cause of the syndrome has been associated with increased androgen serum levels, as well as sympathetic nervous system hyperactivity. The present study analyzed the effects at birth of a single testosterone propionate dose in rats, as well as the role of the superior ovarian nerve in polycystic ovary syndrome persistence. Newborn female rats of the CIIZV strain were injected with a single dose of 100 μg testosterone propionate, or corn oil as a vehicle. At 24 days of age, rats were subjected to superior ovarian nerve unilateral or bilateral section. A group of animals was sacrificed on their first vaginal estrus, and a second group was sacrificed at 90 days of age, when they presented an estrus preceded by a proestrus. Testosterone propionate administration at birth blocked ovulation both in adult animals and in animals sacrificed on the first vaginal estrus. Histological analysis of testosterone propionate-treated adult rat ovaries revealed the development of follicular cysts. Ovulation could not be restored by unilateral or bilateral section, and ovaries presented follicular cyst and absence of corpora lutea. Our results suggest that testosterone propionate treatment at birth results in the development of polycystic ovary syndrome, and that this outcome is not due to superior ovarian nerve noradrenergic innervation hyperactivity.

Highlights

Polycystic ovary syndrome is a complex disorder affecting 6 to 10% of women of reproductive age
In their first vaginal estrus, VEH-treated animals showed a larger number of ova shed by the right ovary compared to ovocytes released by the left ovary (Right ovary: 10.6 ± 0.9 vs. Left ovary: 7.6 ± 0.8; p < 0.05; Kruskal-Wallis test followed by Mann-Whitney U test)
The histological analysis of ovaries from Testosterone propionate (TP)-treated animals showed the development of follicular cysts, a lack of the follicular reserve, and absence of corpora lutea (Fig. 1a)

Summary

Introduction

Polycystic ovary syndrome is a complex disorder affecting 6 to 10% of women of reproductive age. The present study analyzed the effects at birth of a single testosterone propionate dose in rats, as well as the role of the superior ovarian nerve in polycystic ovary syndrome persistence. At 24 days of age, rats were subjected to superior ovarian nerve unilateral or bilateral section. The administration of androgens (testosterone, testosterone propionate, androstenedione) or estrogens (estradiol valerate, EV) is a useful tool to generate animal models developing a type of physiopathology similar to that observed in women with polycystic ovary syndrome (PCOS) [1,2,3,4,5,6,7]. The authors did not fully protect against the development of DHT-induced cystic follicles These results demonstrate that extra ovarian neuroendocrine AR sites of androgen action are predominantly involved in the pathogenesis of PCOS. Our research group has shown that SON unilateral section in animals with EVinduced PCOS restores ovulation in the innervated gonad, but not in the denervated one [30]

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