Fertility & Research Centre, School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia.
Andrology Laboratory, ANZAC Research Institute, University of Sydney, Sydney, New South Wales, Australia.
Endocrinology. 2019 Mar 1;160(3):699-715. doi: 10.1210/en.2018-00966.
Polycystic ovary syndrome (PCOS) is a common cause of female infertility. Hyperandrogenism is both a major symptom and key diagnostic trait of PCOS; however, the direct impact of this androgen excess on ovarian dynamics is unclear. By combining a DHT-induced PCOS mouse model with an ex vivo follicle culture system, we investigated the impact of hyperandrogenism on ovarian function. Ovaries from PCOS mice exhibited the characteristic polycystic ovary morphology with numerous large cystic follicles and no corpora lutea present. Isolation and individual culture of preantral and antral follicles from PCOS mice resulted in slower growth rates during 5 days compared with the follicles isolated from control mice (P < 0.01). In contrast, preovulatory follicles from PCOS mice exhibited a significant increase in growth rate compared with controls (P < 0.01). Preantral follicles from PCOS ovaries maintained comparable follicular health as control follicles, but antral and preovulatory PCOS follicles exhibited reduced follicle health (P < 0.01) and survival rates (P < 0.01). Compared with controls, PCOS females also exhibited a poorer response to hyperstimulation (P < 0.01), impaired oocyte function evident by increased levels of reactive oxygen species (P < 0.01), and a reduction in on-time embryo development (P < 0.01). These results demonstrate that prolonged exposure to androgen excess leads to aberrant follicle development, which persists even after removal from the hyperandrogenic environment, causing perturbed follicular developmental trajectories. These findings indicate that an in vivo hyperandrogenic environment in patients with PCOS may intrinsically induce detrimental effects on follicles and oocytes.
多囊卵巢综合征（PCOS）是女性不孕的常见原因。高雄激素血症既是 PCOS 的主要症状也是关键诊断特征；然而，这种雄激素过多对卵巢动态的直接影响尚不清楚。通过将 DHT 诱导的 PCOS 小鼠模型与体外卵泡培养系统相结合，我们研究了高雄激素血症对卵巢功能的影响。PCOS 小鼠的卵巢表现出多囊卵巢的特征性形态，有许多大的囊性卵泡，没有黄体存在。从 PCOS 小鼠中分离和单独培养原始卵泡和窦前卵泡，与从对照小鼠中分离的卵泡相比，在 5 天内生长速度较慢（P < 0.01）。相比之下，PCOS 小鼠的排卵前卵泡的生长速度与对照组相比显著增加（P < 0.01）。与对照组相比，原始卵泡维持与对照组相当的卵泡健康，但窦前和排卵前 PCOS 卵泡的卵泡健康状况（P < 0.01）和存活率（P < 0.01）降低。与对照组相比，PCOS 雌性动物对超刺激的反应也较差（P < 0.01），活性氧水平升高表明卵母细胞功能受损（P < 0.01），按时胚胎发育减少（P < 0.01）。这些结果表明，长期暴露于雄激素过多会导致异常的卵泡发育，即使在去除雄激素环境后，这种异常仍会持续存在，导致卵泡发育轨迹紊乱。这些发现表明，PCOS 患者体内的高雄激素环境可能会对卵泡和卵母细胞产生内在的有害影响。
