Reproductive and Developmental Sciences Program, Department of Animal Science, Michigan State University, East Lansing, MI, USA.
Biol Reprod. 2022 May 17;106(5):968-978. doi: 10.1093/biolre/ioac021.
High follicle-stimulating hormone (FSH) doses during ovarian stimulation are detrimental to ovulatory follicle function and decrease live birth rate in cattle and women. However, the mechanism whereby excessive FSH causes ovarian dysfunction is unknown. This study tested the hypothesis that excessive FSH during ovarian stimulation induces premature luteinization of ovulatory-size follicles. Small ovarian reserve heifers were injected twice daily for 4 days with 70 IU (N = 7 heifers) or 210 IU (N = 6 heifers) Folltropin-V [commercial FSH-enriched preparation of porcine pituitary glands with minor (<1%) luteinizing hormone (LH) contamination, cpFSH]. Ovulatory-size (≥10 mm) follicles were excised from ovaries after the last cpFSH injection and hormone concentrations in follicular fluid (FF) were determined using ELISA. Luteinization was monitored by assessing cumulus cell-oocyte complex (COC) morphology and measuring concentrations of estradiol (E), progesterone (P), and oxytocin (O) in FF. COCs were classified as having compact (cCOC) or expanded (eCOC) cumulus cell layers, and as estrogen-active (E:P in FF ≥1), estrogen-inactive (EI, E:P in FF ≤1 > 0.1), or extreme-estrogen-inactive (EEI, E:P in FF ≤0.1). A high proportion (72%) of ovulatory-size follicles in 210 IU, but not 70 IU, dose heifers displayed eCOCs. The high doses also produced higher proportions of EI or EEI follicles which had lower E:P ratio and/or E but higher P and/or O concentrations compared with the 70 IU dose heifers. In conclusion, excessive cpFSH doses during ovarian stimulation may induce premature luteinization of most ovulatory-size follicles in heifers with small ovarian reserves.
高卵泡刺激素（FSH）剂量在卵巢刺激期间对排卵卵泡功能有害，并降低牛和妇女的活产率。然而，过量 FSH 导致卵巢功能障碍的机制尚不清楚。本研究检验了这样一个假设，即在卵巢刺激期间过量 FSH 会导致排卵大小卵泡的过早黄体化。小卵巢储备小母牛每天两次注射 70 IU（N=7 头小母牛）或 210 IU（N=6 头小母牛）Folltropin-V[商业 FSH 富集猪垂体制剂，含有少量（<1%）促黄体激素（LH）污染，cpFSH]，连续 4 天。最后一次 cpFSH 注射后，从卵巢中切除排卵大小（≥10 毫米）的卵泡，并使用 ELISA 测定卵泡液（FF）中的激素浓度。通过评估卵丘细胞-卵母细胞复合物（COC）的形态和测量 FF 中雌二醇（E）、孕酮（P）和催产素（O）的浓度来监测黄体化。COC 被分类为具有致密（cCOC）或扩展（eCOC）卵丘细胞层，以及雌激素活性（FF 中 E:P≥1）、雌激素不活性（EI，FF 中 E:P≤1>0.1）或极端雌激素不活性（EEI，FF 中 E:P≤0.1）。在 210 IU 剂量组中，72%的排卵大小卵泡显示出 eCOC，而在 70 IU 剂量组中则没有。高剂量还产生了更高比例的 EI 或 EEI 卵泡，与 70 IU 剂量组的小母牛相比，这些卵泡的 E:P 比值和/或 E 较低，但 P 和/或 O 浓度较高。总之，在小卵巢储备的小母牛中，卵巢刺激期间过量的 cpFSH 剂量可能会导致大多数排卵大小卵泡的过早黄体化。
