Fetal programming of polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects up to 6.8% of reproductive age women. Experimental research and clinical observations suggest that PCOS may originate in the very early stages of development, possibly even during intrauterine life. This suggests that PCOS is either genetically-transmitted or is due to epigenetic alterations that develop in the intrauterine microenvironment. Although familial cases support the role of genetic factors, no specific genetic pattern has been defined in PCOS. Several candidate genes have been implicated in its pathogenesis, but none can specifically be implicated in PCOS development. Hypotheses based on the impact of the intrauterine environment on PCOS development can be grouped into two categories. The first is the "thrifty" phenotype hypothesis, which states that intrauterine nutritional restriction in fetuses causes decreased insulin secretion and, as a compensatory mechanism, insulin resistance. Additionally, an impaired nutritional environment can affect the methylation of some specific genes, which can also trigger PCOS. The second hypothesis postulates that fetal exposure to excess androgen can induce changes in differentiating tissues, causing the PCOS phenotype to develop in adult life. This review aimed to examine the role of fetal programming in development of PCOS.

National and regional trends in the prevalence of polycystic ovary syndrome since 1990 within Europe: the modeled estimates from the Global Burden of Disease Study 2016

“…Low SES may also reduce access to health care, thereby leading to decreased management and treatment of the condition [ 2 ]. Another potential pathway linking SES to the risk of PCOS may be the association between low SES-related intrauterine nutritional restriction and the tendency towards small-for-gestational age at delivery, which some researchers have proposed as one of the initiating factors for fetal programming toward the development of thrifty PCOS phenotype [ 2 , 22 – 25 ] and PCOS-associated metabolic abnormalities in adulthood [ 26 – 28 ], similar to human in utero exposure to androgen access or experimental neonatal exposure to estrogen valerate [ 29 ]. However, the association of low SES with the risk of PCOS seems to be more complex, as some studies have demonstrated that low childhood SES (measured by low parental education) increased the risk of PCOS but that this risk was limited only to those who personally attained a high level of education [ 22 ].…”

Epigenetic modification of long interspersed elements-1 in cumulus cells of mature and immature oocytes from patients with polycystic ovary syndrome

“…In PCOS, the change in methylation levels may alter mRNA and cause the pathophysiology of various diseases. Previous studies demonstrated that the intrauterine environment might contribute to the development of PCOS [ 6 7 8 ] and fetal androgen exposure inside the uterus has been shown to cause epigenetic changes [ 23 ]. This finding affirms the role of environmental impact on epigenetic modification and the development of oocytes.…”

“…A difference in the gene expression profiles in cumulus cells taken from PCOS and control patients has been previously reported [ 5 ]. Moreover, the intrauterine environment might contribute to the development of this syndrome and fetal androgen exposure inside the uterus [ 6 7 8 ] has been shown to cause epigenetic changes leading to the development of PCOS.…”

Shaoyao-Gancao Decoction alleviated hyperandrogenism in a letrozole-induced rat model of polycystic ovary syndrome by inhibition of NF-κB activation

“…In addition to the reproductive abnormalities, affected women are more likely to develop various clinical implications, including hyperandrogenism, cardiovascular disease, and endometrial carcinoma. Despite the high prevalence and marked impact of PCOS in the community, the precise mechanism underlying the pathogenesis of PCOS is still not fully understood [4].…”