Gonçalves Bianca Santos Martins, Mariotti Flora França Nogueira, Ponsone Giovana, Soares Thalita Aparecida Avelino, Perão Paula Cristina Barbosa Garcia, Mônico-Neto Marcos, Cariste Leonardo Moro, Maluf Auro, Nascimento Gustavo da Silva Soares, Antunes Hanna Karen Moreira, Céspedes Isabel Cristina, Viana Milena de Barros, Le Sueur-Maluf Luciana
Departamento de Biociências, Universidade Federal de São Paulo, UNIFESP, 11015-020 Santos, SP, Brazil.
Departamento de Ciências do Mar, Universidade Federal de São Paulo, UNIFESP, 11070-102 Santos, SP, Brazil.
Horm Behav. 2022 Jan;137:105087. doi: 10.1016/j.yhbeh.2021.105087. Epub 2021 Nov 23.
Elevated levels of endogenous ovarian hormones are conditions commonly experienced by women undergoing assisted reproductive technologies (ART). Additionally, infertility-associated stress and treatment routines are factors that together may have a highly negative impact on female emotionality, which can be aggravated when several cycles of ART are needed to attempt pregnancy. This study aimed to investigate the effect of high and fluctuating levels of gonadal hormones induced by repeated ovarian stimulation on the stress response in rodents. To mimic the context of ART, female rats were exposed to an unpredictable chronic mild stress (UCMS) paradigm for four weeks. During this time, three cycles of ovarian stimulation (superovulation) (150 IU/Kg of PMSG and 75 IU/Kg of hCG) were applied, with intervals of two estrous cycles between them. The rats were distributed into four groups: Repeated Superovulation/UCMS; Repeated Superovulation/No Stress; Saline/UCMS; and Saline/No Stress. Anxiety-like and depressive-like behaviors were evaluated in a light-dark transition box and by splash test, respectively. Corticosterone, estradiol, progesterone, and biometric parameters were assessed. Data were analyzed using a two-way Generalized Linear Model (GzLM). Our results showed that repeated ovarian stimulation exerts by itself an expressive anxiogenic effect. Surprisingly, when high and fluctuating levels of ovarian hormones were combined with chronic stress, anxiety-like behavior was no longer observed, and a depressive-like state was not detected. Our findings suggest that females subjected to emotional overload induced by repeated ovarian stimulation and chronic stress seem to trigger the elaboration of adaptive coping strategies.
接受辅助生殖技术（ART）的女性通常会出现内源性卵巢激素水平升高的情况。此外，与不孕相关的压力和治疗程序是可能共同对女性情绪产生高度负面影响的因素，当需要进行多个ART周期来尝试怀孕时，这种影响会加剧。本研究旨在调查反复卵巢刺激诱导的性腺激素高水平和波动对啮齿动物应激反应的影响。为了模拟ART的情况，将雌性大鼠暴露于不可预测的慢性轻度应激（UCMS）范式下四周。在此期间，应用三个卵巢刺激（超排卵）周期（150 IU/Kg的孕马血清促性腺激素和75 IU/Kg的人绒毛膜促性腺激素），其间间隔两个发情周期。将大鼠分为四组：反复超排卵/UCMS；反复超排卵/无应激；生理盐水/UCMS；和生理盐水/无应激。分别在明暗转换箱和通过泼水试验评估焦虑样和抑郁样行为。评估皮质酮、雌二醇、孕酮和生物统计学参数。使用双向广义线性模型（GzLM）分析数据。我们的结果表明，反复卵巢刺激本身会产生明显的致焦虑作用。令人惊讶的是，当卵巢激素的高水平和波动与慢性应激相结合时，未观察到焦虑样行为，也未检测到抑郁样状态。我们的研究结果表明，受到反复卵巢刺激和慢性应激诱导的情绪过载的雌性似乎会触发适应性应对策略的形成。
