Halloran Katherine M, Zhou Yiran, Bellingham Michelle, Lea Richard G, Evans Neil P, Sinclair Kevin D, Smith Peter, Padmanabhan Vasantha
Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
School of Biodiversity One Health and Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, UK.
Biol Reprod. 2025 Feb 14;112(2):331-345. doi: 10.1093/biolre/ioae166.
Developmental exposure to environmental chemicals perturbs establishment and maintenance of the ovarian reserve across the reproductive lifetime, leading to premature follicle depletion and ovarian aging. Considering humans are exposed to a complex mixture of environmental chemicals, real-life models assessing their cumulative impact on the ovarian reserve are needed. Biosolids are a source of a real-life mixture of environmental chemicals. While earlier studies demonstrated that grazing pregnant sheep on biosolids-treated pastures did not influence establishment of the ovarian reserve in fetal life, its impact on subsequent depletion of ovarian reserve during reproductive life of offspring is unknown. We hypothesized that developmental exposure to biosolids accelerates depletion of ovarian reserve. Ovaries were collected from F1 juveniles (9.5 weeks) and adults (2.5 years) born to F0 ewes grazed on control inorganic fertilizer pastures or biosolids-treated pastures from before conception and throughout gestation. The impact on follicular density, activation rate, and anti-Müllerian hormone (mediator of activation) expression by immunohistochemistry was determined. Activation rate was increased in F1 biosolids-treated pastures juveniles with a corresponding reduction in primordial follicle density. In contrast, activation rate and ovarian reserve were similar between control and F1 biosolids-treated pastures adults. The density of anti-Müllerian hormone-positive antral follicles was lower in biosolids-treated pastures juveniles, whereas anti-Müllerian hormone expression tended to be higher in antral follicles of biosolids-treated pastures adults, consistent with the changes in the ovarian reserve. These findings of detrimental effects of developmental exposure to biosolids during juvenile life that normalizes in adults is supportive of a shift in activation rate likely related to peripubertal hormonal changes.
在整个生殖生命周期中，发育阶段接触环境化学物质会扰乱卵巢储备的建立和维持，导致卵泡过早耗竭和卵巢衰老。鉴于人类接触的是复杂的环境化学物质混合物，因此需要真实模型来评估它们对卵巢储备的累积影响。生物固体是环境化学物质真实混合物的一个来源。虽然早期研究表明，在经生物固体处理的牧场上放牧怀孕母羊不会影响胎儿期卵巢储备的建立，但其对后代生殖生命期间卵巢储备后续耗竭的影响尚不清楚。我们假设发育阶段接触生物固体可加速卵巢储备的耗竭。从在受孕前及整个妊娠期在对照无机肥料牧场或经生物固体处理的牧场上放牧的F0母羊所生的F1幼羊（9.5周）和成年羊（2.5岁）中采集卵巢。通过免疫组织化学确定对卵泡密度、激活率和抗苗勒管激素（激活介质）表达的影响。在经生物固体处理的牧场F1幼羊中激活率增加，同时原始卵泡密度相应降低。相比之下，对照和经生物固体处理的牧场F1成年羊之间的激活率和卵巢储备相似。在经生物固体处理的牧场幼羊中，抗苗勒管激素阳性窦卵泡的密度较低，而在经生物固体处理的牧场成年羊的窦卵泡中抗苗勒管激素表达往往较高，这与卵巢储备的变化一致。这些关于幼年时期发育阶段接触生物固体的有害影响在成年后恢复正常的发现支持了激活率的转变可能与青春期前后的激素变化有关。
