Polycystic ovary syndrome resembling histopathological alterations in ovaries from prenatal androgenized female rats

Xia, Wang Fang, Yu Bolan, Yang Wenjing, Liu Jianqiao, Lu Jiachun, Xia Xuefeng

Description

The polycystic ovary syndrome ( PCOS ) affects approximately 6-10% of women of reproductive age and is characterized by chronic anovulation and hyperandrogenism. However, a comprehensive understanding of the mechanisms that dictate androgen overproduction is lacking, which may account for inconsistencies between measures of androgen excess and clinical presentation in individual cases. Methods A rat model of PCOS was established by injecting dehydroepiandrosterone sulfoconjugate (DHEAS) into pregnant females. Rats were administered with DHEAS (60 mg/kg/d) subcutaneously (s.c.) for all 20 days of pregnancy (Group A), or for the first 10 days (Group B), or from day 11 to day 20 (Group C). Controls were administered with injection oil (0.2 ml/day) s.c. throughout pregnancy (Group D). The litter rate, abortion rate, and offspring survival rate in each group were recorded. Serum androgen and estrogen were measured and the morphological features of the ovaries were examined by light and electron microscopy in the offspring of each group. Results We found that rats injected with DHEAS throughout pregnancy (group A) lost fertility. Rats injected with DHEAS during early pregnancy (group B) exhibited more serious aberrations in fertility than both Group C, in which rats were injected with DHEAS during late pregnancy (P < 0.05), and Group D (controls). There was a statistical difference of ovarian weight among female offspring in Group B, C and D (P < 0.01). By light and electron microscopy, a significant morphological difference among the female offspring in the three groups was observed. Conclusions Our results indicate that androgen excess during pregnancy can decrease rat fertility. Excess androgen at the early stage of pregnancy causes high reproductive toxicity, leading to abnormality of ovarian morphology and functions in female offspring.

Sujets

• Ovary

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 12
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

Wanget al. Journal of Ovarian Research2012,5:15 http://www.ovarianresearch.com/content/5/1/15

R E S E A R C HOpen Access Polycystic ovary syndrome resembling histopathological alterations in ovaries from prenatal androgenized female rats 1†1†1 1*2 1 Fang Wang, Bolan Yu, Wenjing Yang , Jianqiao Liu , Jiachun Luand Xuefeng Xia

Abstract Background:The polycystic ovary syndrome(PCOS)affects approximately 610% of women of reproductive age and is characterized by chronic anovulation and hyperandrogenism. However, a comprehensive understanding of the mechanisms that dictate androgen overproduction is lacking, which may account for inconsistencies between measures of androgen excess and clinical presentation in individual cases. Methods:A rat model of PCOS was established by injecting dehydroepiandrosterone sulfoconjugate (DHEAS) into pregnant females. Rats were administered with DHEAS (60 mg/kg/d) subcutaneously (s.c.) for all 20 days of pregnancy (Group A), or for the first 10 days (Group B), or from day 11 to day 20 (Group C). Controls were administered with injection oil (0.2 ml/day) s.c. throughout pregnancy (Group D). The litter rate, abortion rate, and offspring survival rate in each group were recorded. Serum androgen and estrogen were measured and the morphological features of the ovaries were examined by light and electron microscopy in the offspring of each group. Results:We found that rats injected with DHEAS throughout pregnancy (group A) lost fertility. Rats injected with DHEAS during early pregnancy (group B) exhibited more serious aberrations in fertility than both Group C, in which rats were injected with DHEAS during late pregnancy (P<0.05), and Group D (controls). There was a statistical difference of ovarian weight among female offspring in Group B, C and D (P<0.01). By light and electron microscopy, a significant morphological difference among the female offspring in the three groups was observed. Conclusions:Our results indicate that androgen excess during pregnancy can decrease rat fertility. Excess androgen at the early stage of pregnancy causes high reproductive toxicity, leading to abnormality of ovarian morphology and functions in female offspring. Keywords:Prenatal androgenization, Polycystic ovary syndrome (PCOS), Ovarian, Rat model

Background Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in premenopausal women [1]. In different ethic populations, the prevalence of PCOS is about 510% [2,3]. In clinic, PCOS patients are usually diagnosed by a distinguishing polycystic appearance of the ovary and a wide range of biochemical markers including elevated serum androgens, insulin, luteinizing hormone (LH), and decreased insulin sensitivity [4]. Both

* Correspondence: [e-mail] † Equal contributors 1 Institute of Gynecology and Obstetrics, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China Full list of author information is available at the end of the article

healthy women and women with abnormal cycles and hyperandroenism could develop PCOS, however, over weight or obese girls are much more predisposed to PCOS [4,5]. Currently, the etiology of PCOS remains largely unknown. It is believed that both genetic factors and gestational environment contribute to its origin and development, and prenatal androgen exposure is considered one of the important factors in the early origins of PCOS [1,6,7]. It has been found that adrenal androgen excess pre sents in approximately 2560% of women with PCOS, in which dehydroepiandrosterone (DHEA), dehydroepiandros terone sulfoconjugate (DHEAS), and androstenedione are

© 2012 Wang et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.