超排卵对大鼠卵巢组织结构及生殖内分泌的影响

目的: 探讨超排卵对大鼠卵巢组织结构和生殖内分泌功能的影响,为临床合理使用超排卵提供理论依据。方法: 30只雌性SD大鼠随机分为3组: 实验A组接受孕马血清和人绒毛膜促性腺激素重复6次超排卵,实验B组 给予3次生理盐水注射及孕马血清和人绒毛膜促性腺激素重复3次超排卵,对照组接受6次生理盐水注射。15 d及30 d后分别处死各组一半大鼠,观察卵巢组织形态学变化,采用放射免疫法检测血清雌二醇(E₂)、卵泡刺激素(FSH)、黄体生成素(LH)水平,并计算FSH/LH水平,比较各组间的差异。结果: 实验A和B组大鼠卵巢始基卵泡和初级卵泡计数明显低于对照组(P<0.05),但各组大鼠体内血清基础激素水平无显著差异(P>0.05)。结论: 超排卵会引起大鼠卵巢的卵泡发育受限,且随着超排卵次数的增加而加重,但尚未导致生殖内分泌激素水平的显著改变。     

BMP-4在卵巢早衰小鼠卵巢中的变化

目的分析BMP-4在化疗后卵巢早衰(POF)小鼠卵巢中的表达,探索BMP-4与卵巢早衰卵巢中卵泡发育的关系,为卵巢早衰的发病机制及临床治疗的研究提供参考依据。方法选用48只4~5周龄具有正常动情周期的雌性昆明小鼠随机分为3组:POF组,腹腔注射环磷酰胺,皮下注射白消安建立卵巢早衰模型;对照组,腹腔注射0.9%的生理盐水;正常组。观察并记录小鼠的一般情况,应用HE染色、免疫组织化学技术和Western blot技术,观察卵巢形态学变化、各级卵泡数的变化及BMP-4的分布情况。结果 1POF组小鼠体重下降,卵巢体积缩小,HE染色显示卵泡数目减少,原始卵泡数目(15.44±2.16)与正常组(55.25±16.09)和对照组(53.37±18.11)相比明显减少(P0.05)。2免疫组化结果显示BMP-4在正常组卵巢和对照组卵巢中的表达比在POF组卵巢中的表达高。3免疫组化结果显示BMP-4在POF卵巢中的表达明显减少,其中原始卵泡(39.83±6.50)减少最为明显,与正常组(68.61±5.25)和对照组(66.72±6.26)相比差异有统计学意义(P0.05)。4Western blot结果显示POF卵巢中的BMP-4表达最低,约为正常组的0.6倍(P0.05)。结论 POF组的BMP-4表达降低明显,在原始卵泡中降低最为明显,推测其对原始卵泡的存活和发育及调控卵泡闭锁有促进作用。     

卵巢早衰的病因及治疗新进展

卵巢早衰(premature ovarian failure,POF)是多种病因所致的卵巢功能衰竭,危及妇女身心健康,40岁之前POF的发病率为1%～3%[1].以闭经、不孕不育为主要临床表现,伴有雌激素(E2)降低和促卵泡素(FSH)、黄体生成素(LH)升高.POF的发病率逐年上升,治疗困难,病因复杂,日益受到国内外临床医生的关注.现将近年来POF在病因和治疗方面的研究进展做一综述.     

补肾阴及补肾阳法对化疗诱导的卵巢早衰大鼠外周血TNF-α、IFN-γ水平及卵巢颗粒细胞凋亡的影响

目的:观察化疗诱导的卵巢早衰大鼠接受补肾阴法和补肾阳法干预后,其外周血肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)水平及卵巢颗粒细胞凋亡情况。方法:48只雌性SD大鼠随机分成对照(control)组、环磷酰胺(CTX)组、环磷酰胺+补肾阴(CTX+kidney yin)组、环磷酰胺+补肾阳(CTX+kidney yang)组。ELISA法检测各组大鼠外周血TNF-α、IFN-γ水平;末端脱氧核糖核苷酸转移酶介导的缺口末端标记(TUNEL)法检测卵巢颗粒细胞凋亡;Western blot法检测卵巢Bax、Bcl-2蛋白的表达。结果:CTX组大鼠外周血TNF-α、IFN-γ表达水平上升,卵巢颗粒细胞凋亡明显,卵巢中Bax蛋白明显增多,而Bcl-2蛋白明显减少。经本实验中补肾方药治疗后,外周血TNF-α、IFN-γ水平下降,颗粒细胞凋亡程度减轻,Bax蛋白减少,Bcl-2蛋白增多,部分指标变化以CTX+kidney yin组较为明显。结论:补肾阴及补肾阳法可通过调控颗粒细胞凋亡相关的Bax、Bcl-2蛋白及外周血TNF-α、IFN-γ的水平,抑制卵巢颗粒细胞凋亡,恢复卵巢功能、增强储备能力。     

中药木尼孜其对慢性应激型卵巢早衰大鼠性腺轴的影响

目的:通过观察慢性应激所致卵巢早衰大鼠垂体、下丘脑及卵巢的组织形态,探讨中药木尼孜其对慢性应激型卵巢早衰的作用。方法:选用90只性成熟Sprague-Dawley雌性大鼠,随机选取10只设为正常组,其余80只为应激模型组,模型建成之后从中筛选出成卵巢早衰者分为卵巢早衰模型组及卵巢早衰药物干预高、中、低剂量组。运用HE染色及Masson染色观察垂体、下丘脑及卵巢组织形态变化并计算卵巢和子宫指数;用ELISA试剂盒检测大鼠血清中雌二醇(E_2)、卵泡刺激素(FSH)及黄体生成素(LH)的水平。结果:中药木尼孜其对慢性应激致卵巢早衰大鼠的垂体、下丘脑及卵巢组织形态以及激素水平有一定的改善作用。与模型组比较,各药物干预组均有不同程度的改变;与正常组比较,模型组的E_2水平明显降低(P0.05),LH和FSH水平显著升高(P0.05)。结论:慢性应激能够导致卵巢早衰的发生;中药木尼孜其有防治卵巢早衰的作用,能有效改变性腺轴的组织形态及激素水平。     

慢性应激致卵巢早衰大鼠C3 与CYP51 蛋白表达水平比较

目的:制作慢性应激致卵巢早衰大鼠模型并用中药木尼孜其合剂进行药物干预,检测各组大鼠C3与CYP51蛋白表达,为治疗慢性应激型致POF提供依据。方法:选用90只性成熟Wistar雌鼠,随机选取10只设为正常组,其余80只为慢性应激模型组,模型建成之后从中筛选出成卵巢早衰者分为POF模型组(POF组)及POF药物干预高、中、低剂量组。用免疫组织化学技术检测卵巢中C3与CYP51蛋白表达。结果:C3蛋白主要表达在颗粒层细胞及卵泡液中,POF组大鼠较C组表达显著升高(P0. 05),各药物干预组在不同程度上能够降低其表达; CYP51蛋白在各组主要表达在间质以及黄体中,POF组大鼠较C组表达显著下降(P0. 05),各药物干预组在不同程度上能够降升高其表达。结论:慢性应激能够导致POF的发生;POF模型卵巢结构及形态的变化及炎性反应的出现可能是促进POF的重要因素之一;中药木尼孜其合剂可能通过下调C3蛋白、上调CYP51蛋白从而改善慢性应激型卵巢早衰大鼠的卵巢功能。     

D( + )半乳糖对小鼠卵巢功能影响的实验性研究

目的评价D（帕半乳糖代谢作用对性成熟小鼠卵巢功能的影响，并探讨利用半乳糖建立卵巢早衰动物模型的可行性。方法选择8-12w龄SPF级昆明小鼠90只，分为试验组和对照组，各45只，给予半乳糖食物丸和标准食物丸，在饲养的第30d、50d、70d，取血检测小鼠体内半乳糖、E2、FSH水平，并行促排卵检查卵巢功能，光镜观察卵巢组织形态学变化。结果在饲养第70d，与对照组相比，模型组卵巢明显缩小，重量显著降低（P〈0．001）；光镜下，对照组卵巢组织中可见各个阶段的卵泡及黄体，模型组卵巢组织可见大量初级卵泡，但成熟卵泡和黄体数量减少，卵巢血管增生，血管壁增厚，有玻璃样变；饲齐第50d和第70d，模型组血清FSH水平明显高于对照组（P值〈0．001），E：水平明显低于对照组（P值〈0．001）。促排卵后发现模型组小鼠输卵管中成熟卵母细胞数目减少，且明显低于对照组（P值〈0．001）。结论大量半乳糖代谢作用可导致性成熟小鼠卵巢功能提前衰竭，可建立卵巢早衰动物模型，为深入探讨POF患者病理生理提供研究之手段。     

尾悬吊模拟失重对雌性大鼠生殖功能的影响

目的: 探讨模拟失重对雌性大鼠生殖功能的影响及其发生机制,为太空探索者的健康保护提供可借鉴的科学线索。方法: 利用尾部悬吊法建立模拟失重状态大鼠模型;选取Wistar雌性大鼠72只,随机均分为6组,3个实验组分别为:模拟失重7 d组、模拟失重14 d组和模拟失重21 d组;3个对照组是与模拟失重组相对应的自由活动组。应用酶联免疫吸附法(ELISA)检测血清中雌二醇(E₂)、卵泡刺激素(FSH)和黄体生成素(LH)水平;HE染色观察卵巢组织结构,特异性脂褐素染色观察卵巢组织衰老状况;逆转录定量PCR(qRT-PCR)技术检测细胞衰老相关分子端粒酶逆转录酶(TERT)、p53、p16、p21和P27的mRNA表达水平;免疫组织化学方法检测P53、P16、P21和P27的蛋白表达;随机取健康雄性大鼠分别与各组雌性大鼠合笼,比较生育仔鼠数量和存活率。结果: 与各对照组相比, 模拟失重7 d组、14 d组和21 d组大鼠血清中E₂下降,FSH和LH上升(P<0.05);大鼠卵巢组织卵泡数量明显减少,卵巢组织发生细胞衰老现象,细胞衰老相关分子TERT mRNA表达被抑制(P<0.05),衰老相关的细胞周期调控分子p53、p16、p21和p27在mRNA和蛋白水平表达均升高(P<0.05)。各模拟失重组雌性大鼠生育的仔鼠数量较相应的对照组明显减少(P<0.05),仔鼠存活率显著下降(P<0.01)。结论: 尾悬吊模拟失重导致雌性大鼠生殖功能下降,该现象与模拟失重诱导卵巢组织细胞衰老和下丘脑-垂体-卵巢轴内分泌功能紊乱相关。     

雌激素通过KATP通道影响大鼠肠系膜动脉的反应性

目的: 观察雌激素对大鼠肠系膜动脉平滑肌ATP敏感性钾离子通道 (K_ATP 通道)mRNA表达的影响,探讨K_ATP通道在雌激素调节大鼠肠系膜血管反应性中的作用。方法: 雌性SD大鼠48只,体重(100±10) g,随机分为假手术组(sham)、卵巢切除组(Ovx)和卵巢切除后补充雌激素组(Ovx +E)。采取实时荧光定量PCR检测大鼠肠系膜动脉中K_ATP通道mRNA的表达;观察各组大鼠肠系膜动脉对去甲肾上腺素(NE)升压效应的反应性。结果: 与sham组相比,Ovx组大鼠肠系膜动脉K_ATP 通道的Kir6.1及SUR2B亚单位mRNA表达减少(P<0.05),而Ovx+E组则表达增加(P<0.05)。与sham组相比,Ovx组大鼠的血管反应性明显增加(P<0.05),Ovx+E组无明显差异。给予K_ATP通道阻滞剂格列本脲后,sham组和Ovx+E组的动脉反应性增加(P<0.05),Ovx组无明显变化(P>0.05),此时3组间比较无明显差异(P>0.05)。结论: 雌激素可能通过上调肠系膜动脉平滑肌细胞K_ATP通道的表达来降低动脉对去甲肾上腺素升压效应的反应性。     

人脐血单个核细胞对半乳糖卵巢早衰小鼠卵巢功能的影响

目的探讨人脐血单个核细胞(HCMNCs)对半乳糖卵巢早衰小鼠动情周期及雌二醇(E2)、卵泡刺激素(FSH)、黄体生成激素(LH)的影响,评价卵巢功能的恢复情况。方法将120只雌性SPF级昆明小鼠随机分为A(半乳糖卵巢早衰+HCMNCs组)、B(半乳糖卵巢早衰组)、C(空白对照组)三组,每组40只。采用给昆明小鼠饲喂35%半乳糖建立半乳糖卵巢早衰小鼠动物模型,聚蔗糖密度梯度离心法制备HCMNCs悬液。造模成功后,A组小鼠双侧卵巢内分别注入10μl HCMNCs悬液;B组小鼠双侧卵巢内注入等量L-DMEM培养液;C组未行任何处理。移植后50 d,ELISA法测定昆明小鼠血清雌二醇(E2)、卵泡刺激素(FSH)及黄体生成激素(LH)变化情况。结果 HCMNCs移植前,A、B组与C组比较,动情周期紊乱率升高、血清E2降低、FSH及LH升高,差异均有统计学意义(P0.05)。HCMNCs移植后,A组动情周期紊乱率下降、血清E2升高,FSH及LH降低,与移植前比较差异均有统计学意义(P0.05);A组与C组移植后比较,动情周期紊乱率、E2、FSH及LH无明显差异(P0.05);A、C组与B组移植后比较,动情周期紊乱率、E2、FSH及LH有统计学差异(P0.05)。结论 HCMNCs能促进半乳糖卵巢早衰小鼠卵巢功能的恢复。     

Human umbilical cord mesenchymal stem cells improve morphometric and histopathologic changes of cyclophosphamide-injured ovarian follicles in mouse model of premature ovarian failure

BackgroundMesenchymal stem cells have restorative effects on premature ovarian failure (POF). The aim of this study was to investigate the effects of human umbilical cord vein MSCs (hUCV-MSCs) on follicular quantitative parameters and histological changes of ovaries in the cyclophosphamide (CTX)-induced POF in mice.Materials and methodsC57BL/6 mice were divided into three groups (10 mice in each group). In the control group, phosphate-buffered saline (PBS) was injected via tail vein following 15 days injection of PBS intraperitoneally (IP). In the CTX group, CTX was administered IP for 15 days and then PBS was injected via tail vein. In the CTX + hUCV-MSCs group, following CTX administration, single dose of the 1 × 10⁶ of hUCV-MSCs were injected into tail vein. H&E, trichrome and PAS staining as well as TUNEL assay were performed on the ovaries tissue sections. The number of follicles, follicular quantitative parameters and apoptotic index were obtained. The serum levels of estradiol and FSH were measured in the mice.ResultsIn the CTX + hUCV-MSCs group, degenerative changes were decreased and follicular quantitative parameters increased in the ovarian follicles compared to the CTX group. In this group number of follicles was increased, apoptotic index was decreased, estradiol and FSH levels were decreased and increased, respectively, all of them improved compared to the CTX group. The mean percentage areas of collagen fibers content were decreased compared to the CTX group.ConclusionResults showed that, hUCV-MSCs administration increases follicular quantitative parameters and improve degenerative changes in the follicles following CTX injury.     

Changes in bradykinin and bradykinin B2-receptor during estrous cycle of mouse

The aim of the study was to investigate changes in the abundance of bradykinin and bradykinin B2-receptor in the ovary of mice during its estrous cycle. Changes in the abundance of bradykinin were correlated with changes in bradykinin B₂-receptor in order to determine the functional significance of this peptide for follicular development, ovulation and luteinization. Bradykinin immunoreactivity was mainly observed in the granulosa cells of antral follicles, especially around the oocytes and lining the antral cavity during proestrus and estrus phases of the cycle. Recently formed corpora lutea showed mild immunoreactivity for both bradykinin and bradykinin B₂-receptor. During diestrus 1 and diestrus 2, bradykinin and bradykinin B₂-receptor immunostaining was mainly found in the corpora lutea and mildly in the antral follicles. Immunoblot analysis for bradykinin and bradykinin B₂-receptor attained a peak during late evening in proestrus, which may be the time of the LH surge. Thereafter bradykinin and bradykinin B₂-receptor declined sharply during the estrus phase. When the concentration of bradykinin was correlated with bradykinin B₂-receptor throughout the estrous cycle, they showed strong positive correlation. Thus, this study indicates that the levels of bradykinin and bradykinin B₂-receptor both simultaneously regulate estrous cycle and are important components for the reproductive process.     

Polyploid cells in the mouse ovary

Cell ploidy in the ovarian follicle and corpus luteum was investigated by DNA in situ hybridization to a reiterated, chromosome 3 transgene in mice that were hemizygous for the transgene. This approach was first validated by analysis of mouse kidney, pancreas and liver control tissues, which contain different frequencies of polyploid nuclei. Polyploid nuclei (with multiple hybridization signals) were seen in histological sections of both ovarian follicles and corpora lutea. The frequency of polyploid nuclei in follicles showed no consistent relationship with age (between 6 weeks and 10 months) but polyploid nuclei were significantly more abundant in corpora lutea than follicles (6.3% vs. 2.5%). This implies that production of polyploid cells is more closely associated with differentiation of ovarian follicles into corpora lutea than with the age of the female. Polyploidy tended to be more frequent in corpora lutea of mice that had mated even if they did not become pregnant. This study has highlighted the presence of polyploid cells in the mouse ovarian follicle and corpus luteum and has identified mating as a possible trigger for polyploidy in the corpus luteum. Further work is required to determine the physiological role of polyploid ovarian cells in reproduction.     

Localization of the progesterone receptor in the porcine ovary

Regulation of progesterone receptor (PR) expression has been studied in many species. However, precise studies have not yet been performed in the porcine ovary. We have examined the localization of PR in follicles and corpora lutea of the porcine ovary at different stages of their development. The effects of LH and FSH on PR expression in granulosa cells of small antral follicles was also studied. Immunohistochemistry was applied to determine the distribution of PR while immunoblot analysis showed that two isoforms A and B were present. Early antral follicles contained PR in the granulosa layer. In granulosa cells of small and medium antral follicles PR was not detected whereas it was present in the theca layer. Before ovulation, PR was found in both granulosa and theca cells of large follicles and the staining intensity was very strong. FSH or LH treatment of small follicles (100 ng/ml) induced changes in cellular distribution patterns of PR. In both cases, PR was expressed in granulosa cells. PR was detected in corpora lutea in all 3 stages of the luteal phase. Our data show that in the pig ovary changes in PR localization are stage-specific and suggest that expression of PR is positively regulated by both LH and FSH.     

Studies of the luteinization process in the rat: development of catecholamine response on progesterone production during the peri-ovulatory period

The present study was undertaken to investigate whether pre-ovulatory follicles have an adrenergic response in terms of progesterone production. Extirpated pre-ovulatory follicles obtained both before and after the endogenous gonadotropin surge and newly formed corpora lutea were obtained from the PMSG rat ovulatory model. Follicles and corpora lutea were incubated for 120 min in MEM with Earle's salt and 10 mM Hepes, 37 degrees C, pH 7.4 and 100% oxygen, with 30 microM noradrenaline or 10 micrograms ml-1 LH-B9). Pre-ovulatory follicles were barely stimulable by noradrenaline, while newly formed corpora lutea responded markedly. Luteinizing hormone (LH) levels significantly increased progesterone accumulation in all groups. In order to determine whether preovulatory follicles need intact surrounding tissue for an adrenergic response on progesterone production, pieces of ovaries containing pre-ovulatory follicles were incubated. No significant effect of noradrenaline or adrenaline was seen, while LH had a substantial effect. The results show that catecholamines acutely exert a selective effect on steroidogenesis in the ovary with a marked stimulatory effect on corpora lutea and a marginal effect on the pre-ovulatory follicle.     

Prostaglandins and corticosterone in the oviparous female lizard,Podarcis sicula sicula,during reproduction

The in vitro effects of prostaglandin F_2α (PGE_2α) and prostaglandin E₂ (PGE₂) on corticosterone release by ovarian follicles, corpora lutea (CL), and interrenals were studies in the female lizard, Podarcis sicula sicula, during reproduction. Follicles and CL were divided according to their different development stages: follicles: pre-vitellogenic, early-vitellogenic, mid-vitellogenic and fully-grown; CL: CL 1 (unshelled eggs in the oviducts), CL2 (shelled eggs in the oviducts), CL3 (eggs laid 6 h previously) and CL4 (eggs laid 48 h previously). Interrenals were divided according to the reproductive stages: pre-vitellogenesis, vitellogenesis, ovulation, post-ovulation, and post-deposition. PGF_2α release was highest in fully-grown follicles and PGE₂ in early-vitellogenic follicles, corticosterone was highest in pre-vitellogenic and lowest in early-vitellogenic follicles. PGE₂ decreased corticosterone in pre-vitellogenic, mid-vitellogenic and fully-grown follicles. PGE_2α release was highest in CL4, and PGE₂ in CL1 and CL2, CL3. In interrenals, PGE_2α release was highest and PGE₂ lowest during ovulation, corticosterone was highest in CL4. PGF_2α increased and PGE₂ decreased interrenal corticosterone during vitellogenesis, ovulation, and post-ovulation. In the plama, PGF_2α levels were highest and PGE₂ lowest during ovulation, corticosterone was highest during ovulation. These results suggest that corticosterone, modulated by PGF_2α and PGE_2α, is implied in the reproductive processes with different roles. In fact this steroid could favour ovulatory and luteolytic processes. In addition the hypothesis of an anti-vitellogenic role of corticosterone in discussed.     

MRL/MpJ-Faslpr mice show abnormalities in ovarian function and morphology with the progression of autoimmune disease

Abstract

The immune system is known to affect reproductive function, and maternal–fetal immune tolerance is essential for a successful pregnancy. To investigate the relationship between autoimmune disease and female reproductive function, we performed a comparative analysis of the ovarian phenotypes for C57BL/6 mice, autoimmune disease-prone MRL/MpJ (MRL/+) mice and congenic MRL/MpJ-Fas^lpr (MRL/lpr) mice harboring a mutation in the Fas gene that speeds disease onset. Both MRL-background strains showed earlier vaginal opening than C57BL/6 mice. The estrous cycle became irregular by 6 and 12 months of age in MRL/lpr mice and mice of the other two strains, respectively. Histological analysis at 3 months revealed that the number of primordial follicles was smaller in MRL-background mice than in C57BL/6 mice after 3 months. In addition, MRL/lpr and MRL/+ mice displayed lower numbers of ovarian follicles and corpora lutea at 3 and 6 months, and 6 and 12 months, respectively, than that in age-matched C57BL/6 mice. MRL/lpr and MRL/+ mice developed ovarian interstitial glands after 3 and 6 months, respectively. In particular, MRL/lpr mice showed numerous infiltrating lymphocytes within the ovarian interstitia, and partially stratified ovarian surface epithelia with more developed microvilli than that observed in C57BL/6 mice at 6 months. No significant differences in serum hormone levels were observed between the strains. In conclusion, MRL/lpr mice display altered ovarian development, morphology and function consistent with the progression of severe autoimmune disease, as these findings are less severe in MRL/+ counterparts.     

Korean medicine treatment for premature ovarian failure: Three case reports

IntroductionPremature ovarian failure (POF) is defined as amenorrhea lasting for more than 4 months before 40 years of age, which is accompanied by a serum follicle-stimulating hormone (FSH) concentration above 40 mlU/mL. POF can cause a series of symptoms associated with low estrogen levels, such as hot flushes, excessive sweating, and infertility. This study aimed to report three cases of POF that were treated successfully with Korean medicine.Case representationThree patients with POF were selected for inclusion in this study. The treatment regimen consisted of herbal medicines, electroacupuncture, moxibustion, and Hominis placental pharmacopuncture. The basic treatment period was 3 months, and follow-up was performed after menstrual recovery. Following treatment, all three patients resumed menstruation without any adverse events. One patient also conceived successfully.ConclusionsThese case reports suggest that Korean medicine could be effective for treating POF. Further preclinical and clinical studies are needed to investigate the mechanism of action of herbal medicines and acupuncture in improving menstruation and FSH levels.     

Immunization against gonadotrophin-releasing hormone: histopathological and hormonal changes in the female rat.

Immunization of female rats against gonadotrophin-releasing hormone (GnRH) resulted in cessation of the oestrus cycles, undetectable serum gonadotrophin levels and a reduction of pituitary gonadotrophin stores and of hypothalamic content of GnRH. Immunization abolished the post-ovariectomy rise in serum levels and in pituitary content of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) without affecting prolactin levels. This suggests that GnRH is involved in the regulation of synthesis as well as the secretion of LH and FSH. Histopathological changes were found in the pituitary, ovaries and uterus of the immunized rats. A marked reduction in the number of gonadotrophs as well as a small decrease in the size of other cells was observed in the pituitaries of rats having high anti-GnRH titres. Rats immunized 5 weeks before castration showed a marked reduction in the number and in the size of castration cells. The ovaries exhibited various degrees of atrophy which were correlated with the anti-GnRH titres. Rats with high anti-GnRH titres revealed extensive atrophy of stromal cells with disappearance of large follicles and corpora lutea; ovaries of rats with low titres of antibodies exhibited small corpora lutea and larger follicles, some of which were cystic. Uteri of rats having high titres of anti-GnRH were severely atrophied with cystic glandular dilation. Uteri of rats with low anti-GnRH titres showed squamous-cell metaplasia and fibrosis of the endometrial stroma.     

The Anovulation in Female Mice Resulting from Postnatal Injections of Estrogen is Correlated with Altered Levels of CD8+ Lymphocytes

PROBLEM: Injections of estradiol-17β (E₂) are known to both induce anovulation and alter lymphocyte maturation in female mice. The current study examined whether the two events are related. METHOD OF STUDY: Female (C3H/HeJ × 129J)F₁ (C31) mice were injected with 20 μg of E₂ from 0–3 days, or from 3–6 days, postpartum. At 8, 12, 20, 32, or 40 weeks of age, the animals were killed, T lymphocytes were characterized, and ovaries were histologically examined for the presence of corpora lutea. RESULTS: Animals injected with E₂ from 0–3 days postpartum had percentages of CD8⁺ thymocytes and CD8⁺ splenocytes that were always lower than in noninjected females, and the E₂-injected animals never ovulated, even by 40 weeks of age. In contrast, animals injected with E₂ from 3–6 days of age had percentages of CD8⁺ thymocytes and CD8⁺ splenocytes that, although initially lower than in control females, attained control values by 32 weeks of age. In addition, at 32 weeks of age a number of the 3–6-day E₂-injected females ovulated, whereas at earlier ages none had. Further, injections of E₂ had little effect on the percentages of CD4⁺ thymocytes and splenocytes in these animals. CONCLUSIONS: The results suggest that E₂-induced anovulation in C31 female mice is correlated with decreased levels of CD8⁺ lymphocytes, and an increased CD4⁺/CD8⁺ lymphocyte ratio.