Prenatal undernutrition affects the phenotypes of PCOS model rats

Abstract

Although polycystic ovary syndrome (PCOS) is among the most common endocrine disorders in women of reproductive age, its etiology remains poorly understood. From the perspective of developmental origins of health and disease, some studies have investigated the relationship between low birth weight and the prevalence of PCOS and/or PCOS phenotypes in humans; however, the results of these studies were inconclusive. Here, we evaluated the effects of prenatal undernutrition on the metabolic and reproductive phenotypes of dihydrotestosterone-induced PCOS model rats. The PCOS model rats showed increased body weight, food intake, fat weight, adipocyte size, and upregulation of inflammatory cytokines in adipose tissue; prenatal undernutrition exacerbated these metabolic changes. Prenatal undernutrition also increased the gene expression of hypothalamic orexigenic factor and decreased the gene expression of anorexigenic factor in the PCOS model rats. In addition, the PCOS model rats exhibited irregular cyclicity, polycystic ovaries, and disrupted gene expression of ovarian steroidogenic enzymes. Interestingly, prenatal undernutrition attenuated these reproductive changes in the PCOS model rats. Our results suggest that in dihydrotestosterone-induced PCOS model rats, prenatal undernutrition exacerbates the metabolic phenotypes, whereas it improves the reproductive phenotypes, and that such phenotypic changes may be induced by the alteration of some peripheral and central factors.

A novel PCOS rat model and an evaluation of its reproductive, metabolic, and behavioral phenotypes

“…Most women with PCOS show enlarged ovaries and PCO, 4 , 14 whereas DHT‐induced PCOS model rats show low ovarian weights and do not always exhibit an increased number of cystic follicles. 9 , 10 , 11 , 12 , 13 In addition, in our preliminary examination it was confirmed that DHT‐induced PCOS model rats had low uterine weights. It is possible that these phenotypic discrepancies between human patients and animal models may hamper the evaluation of the pathophysiology of PCOS at the systemic level.…”

“…Usually, DHT pellets or silicon tubes containing crystalline DHT are used to produce DHT‐induced PCOS animal models. 9 , 10 , 11 , 13 However, we suspected that these procedures may result in DHT having supra‐physiological effects on tissues and organs, and may induce some of the phenotypic discrepancies observed between PCOS animal models and human PCOS, such as small ovaries and uteri. On the contrary, it has been well established that the implantation of a silicon tube containing oil‐dissolved estradiol can reproduce the physiological hormonal milieu in female rodents.…”

Maternal aromatase inhibition via letrozole altered RFamide-related peptide-3 and gonadotropin releasing hormone expression in pubertal female rat

“…Letrozole treated adult female mice revealed an increased neuronal activation of Kiss1 (30). A DHT induced PCOS rat model resulted in decreased kiss1 gene expression, but the serum levels of testosterone, estradiol, LH, FSH were unaltered (31). Interestingly, in a letrozole induced PCOS model in adult rats, increased positivecell number of kisspeptin in the arcuate and decreased number of positive kisspeptin in anteroventral periventricular (AVPV) nucleus were reported (32).…”

Maternal Aromatase Inhibition Effects on RFamide-Related Peptide-3 and Gonadotropin Releasing Hormone in Adult Murine Offspring With Polycystic Ovary Syndrome

“…Letrozole treated adult female mice revealed an increased neuronal activation of Kiss1 (60). A DHT induced PCOS rat model resulted in decreased kiss1 gene expression, but the serum levels of testosterone, estradiol, LH, FSH were unaltered (61). Interestingly, in a letrozole induced PCOS model in adult rats, increased positivecell number of kisspeptin in the arcuate and decreased number of positive kisspeptin in anteroventral periventricular (AVPV) nucleus were reported (62).…”