Transgenerational Inheritance of Reproductive and Metabolic Phenotypes in PCOS Rats

Abstract

Androgen exposure of female fetuses could be an important factor in the development of polycystic ovary syndrome (PCOS) in subsequent generations. The present study aimed to investigate the transgenerational effects of PCOS on the growth, reproduction, and metabolism of the first-and second-generation offspring in rats. Female F0 rats received excessive dehydroepiandrosterone (DHEA) exposure to establish PCOS or the same amount of vehicle as controls. These F0 females were crossed with normal males to obtain control (C) and DHEA (D) F1 offspring, whereas F2 offspring were obtained by inter-crossing between F1 rats for 4 groups: (1) C♂-C♀; (2) D♂-C♀; (3) C♂-D♀ and (4) D♂-D♀. Compared with control groups, F1 and F2 offspring with ancestral DHEA exposure showed higher body weight with increasing age. In addition, female F1 and F2 offspring with ancestral DHEA exposure exhibited PCOS-like reproductive and metabolic phenotypes, including disrupted estrous cycles and polycystic ovaries, as well as increased serum levels of testosterone, impaired glucose tolerance and widespread metabolic abnormalities. Male offspring with ancestral DHEA exposure exhibited lower quality of sperms. These findings confirm the negative effects of excessive androgen exposure of female fetuses on subsequent generations.

Molecular mechanisms underlying altered neurobehavioural development of female offspring of mothers with polycystic ovary syndrome: FOS-mediated regulation of neurotrophins in placenta

“…The sequencing of single metaphase II oocytes from F1-F3 offspring revealed common and unique altered gene expression across all generations [ 82 ]. Female F1 and F2 offspring of rats with ancestral dehydroepiandrosterone exposure exhibited PCOS-like reproductive and metabolic phenotypes, including disrupted oestrous cycles and polycystic ovaries, increased serum levels of testosterone, impaired glucose tolerance, and widespread metabolic abnormalities [ 83 ].…”

Hyperandrogenism and Polycystic ovary syndrome: Effects in pregnancy and offspring development

“…Recent evidence also shows that children born to PCOS mothers could display different reproductive and metabolic alterations (Crisosto et al, 2017;Sir-Petermann et al, 2009). In addition, studies in animal models have also reported intergenerational and transgenerational PCOS-related effects (Risal et al, 2019;H.-L. Zhang et al, 2020). Therefore, in F I G U R E 5 Pregnancy disorders associated with PCOS.…”

“…Among them, the DHEA-induced model, in which female rats are daily exposed to this androgen from the prepubertal F I G U R E 6 PCOS animal models of transgenerational effects. Three different animal models have been used to evaluate PCOS-related inter-and transgenerational effects in females (Risal et al, 2019, H.-L. Zhang et al, 2020, Mimouni et al, 2021, Risal et al, 2021. All of them showed that hormonal induced PCOS-like features could affect different subsequent generations.…”

“…age (day 27) until pubertal stage after sexual maturity is reached (day 46) (H.-L. Zhang et al, 2020). By using this model, the authors found alterations in two subsequent generations of animals.…”

Therapeutic effects of aqueous extract of bioactive active component of Ageratum conyzoides on the ovarian-uterine and hypophysis-gonadal axis in rat with polycystic ovary syndrome: Histomorphometric evaluation and biochemical assessment

“…The primary cause of glucose metabolic disease is insulin resistance (IR), which is also thought to be a key factor in the development of PCOS, which is strongly linked to concurrent metabolic difficulties [ 3 ].Low insulin sensitivity, often known as IR, is a syndrome that causes compensatory hyperinsulinemia and plays a significant role in the etiology of type 2 diabetes [ 4 ]. Increased levels of testosterone and luteinizing hormone are released as a result of hyperinsulinemia, which disrupts the uptake and utilization of glucose and results in prolonged anovulation [ 9 ].Allopathic medications such as clomiphene citrate, metformin, letrozole, tamoxifen, and troglitazone are now the most well-known treatments for PCOS [ 13 ]. Hot flushes, arthritis, joint or muscular discomfort, and psychological side effects such as irritability, mood swings, sadness, and bloating are all common adverse effects of allopathic drugs [ 14 ].…”