性別偏見一直是生物醫學研究領域上的重大議題，尤其是在神經科學方面。在以囓齒動物進行的研究中，許多科學家只關注在雄性動物，因為他們認為雌性動物的動情週期會在實驗中產生巨大的變異程度，然而，對於動情週期是否真的會影響女性行為的研究還很稀少。最近的幾篇論文分析了先前的研究，顯示出並沒有足夠的證據去表明女性擁有比男性還高的變異程度。為了更加了解動情週期對女性變異程度的影響，我們比較了四個近交品系母鼠C57BL/6, BALB/c, C3H, and DBA/2在estrus 和diestrus階段時的行為。我們使用了空曠場地測試、強迫游泳測試及居住者-入侵者實驗去分別觀察焦慮樣、憂鬱樣行為和社交互動，但是我們並沒有發現母鼠在這兩階段的行為表現有顯著差異。另一方面，品系之間的行為差異在estrus和diestrus階段也相對一致，表示動情週期對檢測行為差異的影響非常小。最後，我們比較了公鼠與母鼠之間的行為變異程度，發現兩者的變異程度是非常相似的。總體而言，我們的結果顯示了並沒有證據表明女性的行為會受動情週期影響，並且兩性之間的行為變異程度是相同的，因此在未來的行為研究中，母鼠沒有理由被排除在實驗設計中。

Sex bias has been an issue in many biomedical fields, especially in neuroscience. In rodent research, many scientists only focused on male animals due to the belief that female estrous cycle gives rise to unacceptable, high levels of variance in the experiments. However, the studies on the effect of the estrous cycle on the behavior of mice were still relatively sparse. Recent reviews analyzing previous literature even suggested that there is no evidence for larger variation in female than male in several phenotypes. To further investigate the influence of estrous cycle on female variability, in this study, we compared multiple behaviors between females in estrus and diestrus stages in four different mice strains, C57BL/6, BALB/c, C3H, and DBA/2. We performed the open field test, forced swimming test, and resident-intruder assay to assess anxiety-, depression-like behavior, as well as social interaction respectively but found no any significant difference between females in these two stages. On the other hand, the difference in behaviors among these strains are relatively consistent in both stages, suggesting very minimal effect of estrous cycle for detecting the behavioral difference. Last, we compared the behavioral variation between male and female and found very similar variations in most behaviors between the two sexes. Together, our data showed no evidence that female behaviors are affected by estrous cycle, and most behaviors are equally variable between the two sexes. Female mice, therefore, has no reason to be excluded in future behavioral research.

摘要…………………………………………………………………………………i
Abstract………………………………………………………………………………ii
致謝…………………………………………………………………………………iII
Contents………………………………………………………………………………..1
Figure contents………………………………………………………………………..3
Table contents………………………………………………………………………….4
Abbreviation list………………………………………………………………………5
Introduction……………………………………………………………………………6
1. Sex bias in basic research…………………………………………………….6
2. Sex bias in animal research…………………………………………………..6
3. Estrous cycle in mice…………………………………………………………7
4. Research aim………………………………………………………………....8
Materials and Methods……………………………………………………………….10
1. Animals……………………………………………………………………..10
2. Estrous cycle examination…………………………………………………..11
3. Behavioral tests……………………………………………………………..11
4. Statistical analyses…………………………………………………………..12
Results………………………………………………………………………………..14
1. The estrous cycle has no significant influence on female mouse behaviors..14
2. The behavioral differences among four strains were similar between estrus and diestrus females………………………………………………………..15
3. Similar behavioral variation between males and females…………………..15
Discussion……………………………………………………………………………17
1. Summary……………………………………………………………………17
2. Male mice showed different behavioral type with females………………..17
3. Estrous cycle brings minimal influence on behavior……………………….18
4. Similar behavioral variation between male and female mice………………19
5. Conclusion………………………………………………………………….19
References……………………………………………………………………………21
Figures ……………………………………………………………………………….27
Table …………………………………………………………………………………36

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