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Review
. 2020 Jan;159(1):R1-R13.
doi: 10.1530/REP-19-0197.

Mechanisms of intergenerational transmission of polycystic ovary syndrome

Daniel A Dumesic  1 , Luis R Hoyos  1 , Gregorio D Chazenbalk  1 , Rajanigandha Naik  1 , Vasantha Padmanabhan  2 , David H Abbott  3
Affiliations
Review

Mechanisms of intergenerational transmission of polycystic ovary syndrome

Daniel A Dumesic et al. Reproduction. 2020 Jan.

Abstract

Developmental origins of adult disease (DoHAD) refers to critical gestational ages during human fetal development and beyond when the endocrine metabolic status of the mother can permanently program the physiology and/or morphology of the fetus, modifying its susceptibility to disease after birth. The aim of this review is to address how DoHAD plays an important role in the phenotypic expression of polycystic ovary syndrome (PCOS), the most common endocrinopathy of women characterized by hyperandrogenism, oligo-anovulation and polycystic ovarian morphology. Clinical studies of PCOS women are integrated with findings from relevant animal models to show how intergenerational transmission of these central components of PCOS are programmed through an altered maternal endocrine-metabolic environment that adversely affects the female fetus and long-term offspring health. Prenatal testosterone treatment in monkeys and sheep have been particularly crucial in our understanding of developmental programming of PCOS because organ system differentiation in these species, as in humans, occurs during fetal life. These animal models, along with altricial rodents, produce permanent PCOS-like phenotypes variably characterized by LH hypersecretion from reduced steroid-negative feedback, hyperandrogenism, ovulatory dysfunction, increased adiposity, impaired glucose-insulin homeostasis and other metabolic abnormalities. The review concludes that DoHAD underlies the phenotypic expression of PCOS through an altered maternal endocrine-metabolic environment that can induce epigenetic modifications of fetal genetic susceptibility to PCOS after birth. It calls for improved maternal endocrine-metabolic health of PCOS women to lower their risks of pregnancy-related complications and to potentially reduce intergenerational susceptibility to PCOS and its metabolic derangements in offspring.

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Conflict of interest statement

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Figures

Figure 1.
Figure 1.
Timing of developmental programming of critical target tissues in a) rhesus monkeys, b) sheep and c) humans as precocial species (Padmanabhan and Veiga-Lopez, 2013, Abbott et al., 2005).
Figure 1.
Figure 1.
Timing of developmental programming of critical target tissues in a) rhesus monkeys, b) sheep and c) humans as precocial species (Padmanabhan and Veiga-Lopez, 2013, Abbott et al., 2005).
Figure 1.
Figure 1.
Timing of developmental programming of critical target tissues in a) rhesus monkeys, b) sheep and c) humans as precocial species (Padmanabhan and Veiga-Lopez, 2013, Abbott et al., 2005).
Figure 2.
Figure 2.. Hypothetical model of androgen actions on subcutaneous abdominal adipogenesis in normal-weight PCOS women.
In this model, androgen 1) inhibits preadipocyte differentiation to mature adipocytes, 2) blocks catecholamine-induced lipolysis and 3) impairs insulin-inhibition of lipolysis. Exaggerated adipose stem cell (ASC) development to adipocytes also occurs via androgen-independent mechanisms. Theoretically, exaggerated ASC lipid accumulation within a hyperandrogenic environment could predispose PCOS women to lipotoxicity. A: Commitment; B: Differentiation/lipid accumulation; C: Lipolysis
See this image and copyright information in PMC

References

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MeSH terms