Mother-Infant Department, Institute of Obstetrics and Gynecology, University of Modena and Reggio Emilia, 41100 Modena, Italy.
Department of Biomedical, Metabolic and Neural Sciences, Section of Human Morphology, University of Modena and Reggio Emilia, Modena, Italy.
Horm Mol Biol Clin Investig. 2020 Apr 17;41(2):hmbci-2019-0074. doi: 10.1515/hmbci-2019-0074.
Background Gonadotrophins exert their functions by binding follicle-stimulating hormone receptor (FSHR) or luteinizing hormone and human chorionic gonadotropin receptor (LHCGR) present on endometrium. Within ovaries, FSH induces autophagy and apoptosis of granulosa cells leading to atresia of non-growing follicles, whereas hCG and LH have anti-apoptotic functions. Endometrial cells express functioning gonadotrophin receptors. The objective of this study was to analyze the effect of gonadotrophins on physiology and endometrial cells survival. Materials and methods Collected endometria were incubated for 48 or 72 h with 100 ng/mL of recombinant human FSH (rhFSH), recombinant human LH (rhLH) or highly purified hCG (HPhCG) alone or combined. Controls omitted gonadotrophins. The effect of gonadotrophins on cytochrome P450 family 11 subfamily A polypeptide 1 (CYP11A1), hypoxia inducible factor 1α (HIF1A), and cell-death-related genes expression was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Immunohistochemistry for microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) and apoptotic protease activating factor 1 (APAF-1) was performed. Results Gonadotrophins are able to modulate the endometrial cells survival. FSH induced autophagy and apoptosis by increasing the relative expression of MAP1LC3B and FAS receptor. In FSH-treated samples, expression of apoptosis marker APAF-1 was detected and co-localized on autophagic cells. hCG and LH does not modulate the expression of cell-death-related genes while the up-regulation of pro-proliferative epiregulin gene was observed. When combined with FSH, hCG and LH prevent autophagy and apoptosis FSH-induced. Conclusions Different gonadotrophins specifically affect endometrial cells viability differently: FSH promotes autophagy and apoptosis while LH and hCG alone or combined with rhFSH does not.
促性腺激素通过结合子宫内膜上的卵泡刺激素受体（FSHR）或黄体生成素和人绒毛膜促性腺激素受体（LHCGR）发挥作用。在卵巢内，FSH 诱导颗粒细胞发生自噬和凋亡，导致非生长卵泡闭锁，而 hCG 和 LH 具有抗凋亡作用。子宫内膜细胞表达有功能的促性腺激素受体。本研究旨在分析促性腺激素对生理和子宫内膜细胞存活的影响。
收集子宫内膜，分别用 100ng/ml 的重组人 FSH（rhFSH）、重组人 LH（rhLH）或高纯度 hCG（HPhCG）单独或联合孵育 48 或 72 小时。对照组不添加促性腺激素。通过逆转录定量聚合酶链反应（RT-qPCR）评估促性腺激素对细胞色素 P450 家族 11 亚家族 A 多肽 1（CYP11A1）、缺氧诱导因子 1α（HIF1A）和细胞死亡相关基因表达的影响。采用微管相关蛋白 1A/1B 轻链 3B（MAP1LC3B）和凋亡蛋白酶激活因子 1（APAF-1）的免疫组织化学法进行检测。
促性腺激素能够调节子宫内膜细胞的存活。FSH 通过增加 MAP1LC3B 和 FAS 受体的相对表达诱导自噬和凋亡。在 FSH 处理的样本中，检测到凋亡标志物 APAF-1 的表达，并与自噬细胞共定位。hCG 和 LH 不调节细胞死亡相关基因的表达，而观察到促增殖的表皮调节素基因的上调。当与 FSH 联合使用时，hCG 和 LH 可防止 FSH 诱导的自噬和凋亡。
不同的促性腺激素对子宫内膜细胞活力的影响不同：FSH 促进自噬和凋亡，而单独使用 LH 和 hCG 或与 rhFSH 联合使用则不会。
