Abstract
Simple SummaryIt is well documented that a hypoxic environment at high altitudes decreased the fertility of female domestic animals because of embryonic or fetal losses, intrauterine growth restriction, and birth weight reduction. However, little study has been performed on for the effects of hypoxia on bovine ovary function. In this study, we found that the hypoxia plays an important role in regulating follicular survival and genes expression. Hypoxia limits the growth of bovine follicles cultured in vitro through inhibition of ERα, which could provide useful information for future studies relating to reproduction of cattle.Female animals living in the Qinghai-Tibet Plateau have lower ovulation rates because of the hypoxic environment, however, the mechanism of hypoxia on animal follicles is unclear. In this study, the effects of hypoxia on bovine follicles were investigated using an in vitro follicular culture system. The results show that there was a significant decrease in follicular diameter from day 3 to day 6 in both hypoxia and hypoxia with estrogen (E2) and fulvestrant (ICI 182780) (hypoxia + E2 + ICI) groups, when compared with a normoxia group (p < 0.05). We also observed significant downregulation of ERα and FSHR, while upregulation of LHCGR expression in the hypoxia group and hypoxia + E2 + ICI groups compared to the normoxia group (p < 0.05). The expression of IGF1 gene was significantly downregulated in hypoxia + E2 + ICI group when compared to the hypoxia + E2 group (p < 0.05). The expression of HIF1A, ADAMTS1, VEGFA, and EDN2 were upregulated in both hypoxia and hypoxia + E2 + ICI groups in comparison to normoxia group (p < 0.05). Under hypoxic conditions, the addition of E2 resulted in a decrease of HIF1A protein but an increase of ERα protein in cultured bovine follicles (p < 0.05). In summary, hypoxia limits the growth of bovine follicle cultured in vitro through inhibition of ERα.
Highlights
It is well documented that the fertility of female domestic animals raised at high altitude is reduced in comparison to those raised at low altitude due to the hypoxic environment [1,2]
From day three to six days, the reduced increase in follicular diameter was significant in both groups of hypoxia and hypoxia + E2 + ICI in compared to control group (p < 0.05), but no difference was found between the hypoxia and hypoxia + E2 + ICI groups (p > 0.05)
Transcription of ERα, FSHR, LHCGR, and IGF1 genes were quantified in bovine ovarian follicles (Figure 1) and the results show that hypoxia significantly downregulates ERα and FSHR
Summary
It is well documented that the fertility of female domestic animals raised at high altitude is reduced in comparison to those raised at low altitude due to the hypoxic environment [1,2]. Animals 2019, 9, 551 published papers have shown that reproductive efficiency can be compromised by deficiencies in preovulatory follicle development in sheep raised at high altitude [4] and in mice, as shown using a hypoxic follicular culture system [5]. The crucial role of ERα on folliculogenesis and ovulation has been confirmed in vivo, as there is no corpus luteum (CL) in the ovaries of ERα-deficient mice stimulated with human chorionic gonadotropin (hCG) [7]. ERα is regulated by hypoxia in endometriosis [8], adipose tissues [9], and human embryonic kidney cells [5,10] in different ways, but there are limited studies on the role of hypoxia on ERα in ovarian follicles
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