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Summary in Japanese
過去数十年間の産乳能力を重視した乳牛の遺伝的改良により、乳期当たりの乳量は
増加を続けてきた。その結果、高泌乳牛では分娩後の負のエネルギーバランスに伴い
血液中の遊離脂肪酸（FFA）濃度が上昇し、この高濃度 FFA により種々の疾病および
細胞の機能障害が誘発される。通常、細胞内に流入した過剰な FFA は毒性の無い脂
質の貯蔵形態であるトリアシルグリセロール（TAG）に変換される。しかし、細胞の
処理能力を超える過剰な FFA が流入すると、FFA は細胞内に蓄積し、細胞毒性を引
き起こす。実際に、高濃度の FFA を添加して牛卵子を培養すると、卵子に脂質毒性
が発現することが報告されている。液体クロマトグラフィー質量分析法（LC/MS）を
用いて泌乳牛の卵子の FFA と TAG の組成を調べることは、卵子への脂質毒性の可能
性について調査するために有用な方法であるが、これまでに泌乳牛の卵子の FFA と
TAG の組成を調べた報告はない。そこで本研究で、特に分娩後早期の牛卵子の脂質
毒性について評価するために、泌乳牛の血液と卵子のエネルギー代謝関連脂質（FFA
および TAG）の組成を調べて泌乳ステージ間で比較した。第 1 章では産乳量の少な
い放牧主体の牛群（平均 305 日乳量 7,710 kg）を、第 2 章では産乳量の多い濃厚飼料
主体で飼養される牛群（平均 305 日乳量 9,123 kg）を用いて、卵子の FFA と TAG を
調べた。
第 1 章では、3 つの泌乳ステージにあるホルスタイン種 14 頭を用いた。泌乳初期
群（分娩後 25～47 日、n = 6）、泌乳ピーク群（分娩後 61～65 日、n = 4）、泌乳中期群
（分娩後 160～202 日、n = 4）、および 未経産牛（n = 4、コントロール群）から血漿
および卵子サンプルをそれぞれ尾静脈穿刺と経腟採卵法（OPU）により採取した。サ
ンプル当たり 100 μL の血漿および 5 個の卵子を用いて LC/MS により FFA と TAG の
組成を定性的、半定量的に解析した。その結果、血漿と卵子で合計 6 種類の FFA お
よび 45 種類の TAG が同定された。血漿 FFA 濃度と卵子 TAG 量は正の相関を示した
（r = 0.55、P < 0.05）。泌乳初期群は未経産牛よりも卵子 TAG 量が高く（P < 0.05）
泌乳ピーク群と泌乳中期群はその中間の卵子 TAG 量を示した。しかし、卵子 FFA 量
はいずれの泌乳期においても同程度であった。クラスター解析により、血漿と卵子の
FFA と TAG は 5 種類のグループ：（1）二重結合数 0 の飽和 FFA、（2）二重結合数 1
または 2 の不飽和 FFA、
（3）炭素数 44～48 の TAG、
（4）炭素数 50～54 の TAG およ
び（5）炭素数 56～58 の TAG に分類された。脂肪酸の構成割合に関しては、泌乳初
期群と泌乳ピーク群では泌乳中期群と未経産牛に比べて、血漿中のステアリン酸
（FFA 18:0）の割合が低く、オレイン酸（FFA 18:1）の割合が高かった（P < 0.05）。し
かし、卵子 FFA と卵子 TAG の脂肪酸組成に関しては、泌乳期のステージによる差異
は殆どなかった。以上の結果より、放牧主体で飼養される泌乳初期の牛では、未経産
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牛に比べて卵子 TAG 量が増加したが、卵子 FFA 量は増加しなかった。卵子内で貯蔵
できる TAG 量には限界があることから、泌乳初期の牛の卵子の TAG の増加は、卵子
における過剰な FFA を TAG に変換して貯蔵する能力の低下と、それに伴う卵子の脂
質毒性のリスク増加を示唆した。
一方で、近年の高泌乳牛の典型的な飼養形態は濃厚飼料主体の飼養であり、放牧牛
に比べて摂取エネルギー、消費エネルギーともに大きい代謝状態を示す。このような
エネルギー代謝の違いは卵子の脂質組成に影響する可能性があるため、濃厚飼料主体
で飼養される牛の卵子の脂質組成を調べる必要がある。
第 2 章では、濃厚飼料主体で飼養されていた 4 つの泌乳ステージにあるホルスタイ
ン種 20 頭を用いた。分娩後 20～30 日群（n = 5）、分娩後 40～50 日群（n = 5）、分娩
後 60～80 日群（n = 5）および分娩後 130～160 日群（n = 5）から、第 1 章と同様の方
法で、血漿と卵子のサンプルを採取し、LC/MS により FFA と TAG の組成を解析し
た。採卵前のエネルギーバランスと卵子の脂質との関係について調べるために、供試
牛の OPU 前 3 週間の毎日のエネルギーバランスを計算した。血漿 FFA 濃度は分娩後
20～30 日で高く、50 日までに低下し、それ以降の供試期間中は低いレベルを維持し
た。卵子の FFA 量と TAG 量は、分娩後日数に伴う血漿 FFA の変化と同様の変化を示
した。血漿 FFA 濃度と卵子 FFA 量（r = 0.63）、卵子 FFA 量と卵子 TAG 量（r = 0.46）
の間にそれぞれ正の相関が見られた（P < 0.05）。さらに、卵子 FFA 量は OPU 前 21 日
間、14 日間および 7 日間の平均エネルギーバランスとそれぞれ負の相関を示し（そ
れぞれ r = -0.70、r = -0.64 および r = -0.58、P < 0.05）、その程度は OPU 前のエネルギ
ーバランスを調べた期間が長いほど卵子 FFA 量と強い負の相関を示した（r = -0.70、
P < 0.05）。卵子 FFA 量は、卵子 FFA 不飽和化マーカー（飽和 FFA を単価不飽和 FFA
に変換する不飽和化反応の活性の指標）である FFA 16:1/16:0 比および FFA 18:1/18:0
比とそれぞれ正の相関を示した（それぞれ r = 0.79 および r = 0.56、P < 0.05）。また、
血漿と卵子の FFA 16:1/16:0 比（r = 0.70）および血漿と卵子の FFA 18:1/18:0 比（r =
0.51）の間にも、それぞれ正の相関が見られた（P < 0.05）。すなわち、血漿と卵子で
同様の FFA の量と組成の関係が示された。
本研究は異なる泌乳ステージの牛の卵子の脂質組成を調べた初の研究であり、その
結果、濃厚飼料主体で飼養される牛における分娩後早期の卵子の FFA と TAG の増加
および FFA 不飽和化の活性化が示された。これらの知見は、特に濃厚飼料主体で飼
養される高泌乳牛において、分娩後早期の卵子に FFA の脂質毒性がある可能性を示
唆するものであった。今後、分娩後早期の牛の卵子への脂質毒性がその後の繁殖性に
及ぼす影響について調査するために、卵子中の活性酸素種の産生や小胞体ストレス等
の脂質毒性の有無および程度について明らかにする必要がある。
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