大鼠双侧卵巢自体异位移植的功能研究

目的　为了模拟在体卵巢释放激素的生理功能 ,将成年大鼠的双卵巢切除后行自体腹腔移植 ,观察其移植效果 ,为临床卵巢移植提供实验依据 ,探索治疗围绝经期综合征的新途径。方法　将性成熟的 SD雌性大鼠的双侧卵巢切除 ,两个卵巢立即行自体腹腔移植 ,通过观察阴道脱落细胞变化、子宫角形态及测定血清雌激素水平 ,了解移植后大鼠的内分泌情况 ,判断移植成功与否以及内分泌功能如何。结果　移植组阴道脱落细胞 7/8显示有雌激素分泌 ,子宫角形态及血清的雌激素水平明显优于去势组 (P <0 .0 5 ) ,与正常组差异无显著性 (P>0 .0 5 )。结论　新鲜卵巢自体移植后 ,能分泌雌激素 ,并作用于靶器官维持其功能 ,为临床卵巢移植提供了实验依据。卵巢移植有可能成为临床治疗卵巢内分泌功能不足的新方法。     

大鼠卵巢组织冷冻复苏及自体异位移植研究

目的：探讨直接覆盖玻璃化冷冻(direct cover vitrification, DCV)在冷冻大鼠卵巢组织中的效果,并对自体异位移植后卵巢组织存活状况及内分泌情况进行分析。方法性成熟的 Wistar 大鼠50只随机分为 A、B、C、D 组, A 和 B 组各20只,C 和 D 组各5只。 A 组为新鲜卵巢组织移植;B 组卵巢组织经 DCV 冷冻保存2周复苏后移植;C 组为去势对照;D 组为假手术对照。自体异位移植6周后检测大鼠血清中雌二醇(E2)水平,计算卵泡密度,观察移植卵巢组织形态学及增殖细胞核抗原(proliferating cell nuclear antigen, PCNA)的表达情况。结果大鼠卵巢组织移植存活的卵巢组织周围可见血管供应,移植失败的卵巢组织呈纤维化状态,与周围组织血供不明显。 B 组卵巢组织移植存活率低于 A 组(P <0．05)。 B 组卵巢组织中卵泡密度均低于 A、D 组,且 A 组低于 D 组(P <0．05)。 A、B 组血清 E2水平高于 C 组,低于 D 组(P <0．05)。 A、B 组卵巢组织 PCNA 阳性率均低于 D 组,且 B 组低于 A 组(P <0．05)。结论大鼠卵巢组织经 DCV 法冻融自体异位移植后部分卵泡能存活并可恢复内分泌功能。     

促卵泡激素和血管内皮生长因子在大鼠卵巢组织冷冻自体异位移植中的保护作用

目的：探讨促卵泡激素(FSH)和血管内皮生长因子(VEGF)在大鼠卵巢组织冷冻自体异位移植后对卵泡内分泌功能的影响。方法 Wistar 大鼠30只随机分为 A、B、C 组,每组10只,A 组为新鲜卵巢组织移植,B 组和 C 组卵巢组织均直接覆盖玻璃化冷冻保存2周复苏后移植,但 C 组在移植前2 d 肌内注射 FSH 和 VEGF,连续用药5 d。移植6周后计算卵泡密度;检测大鼠血清中雌二醇(E2)水平;卵巢组织增殖细胞核抗原(PCNA)的表达情况,并测定子宫重量。结果 A、B、C 组移植后卵巢组织存活率比较差异无统计学意义(P >0．05)。 A、C 组卵泡密度、血清 E2水平、PCNA 阳性率和子宫重量均高于 B 组(P <0．05),A 组和 C 组比较差异无统计学意义(P >0．05)。结论大鼠卵巢组织冷冻复苏自体异位移植前注射 FSH 和 VEGF 可以有效提高卵泡存活率,有利于恢复卵巢内分泌功能。     

人窦前小卵泡异种移植后卵泡生长及再血管化的评估

目的评价人卵巢组织经酶消化后分离的窦前小卵泡异种移植到SCID小鼠后的卵泡生长和再血管化情况。方法采用0.04 mg/ml Liberase酶消化卵巢组织,将卵泡吸出,尽可能将全部间质去除,异种移植到卵巢囊,通过病理组织学检查移植物切片中的卵泡分级和形态,用CD34双重免疫组化染色了解移植物中再血管化的情况。结果移植后1、3及22周移植物中均可见到原始卵泡、中间型卵泡、初级卵泡和次级卵泡。移植后1周的移植物中,已经可以见到来源于小鼠和人的微血管,至移植后3周,微血管丰富,向移植物中心生长,在经过促卵泡生成素刺激后的22周,次级卵泡及小窦卵泡周围围绕丰富的毛细血管网。结论人卵巢组织酶解后的窦前小卵泡移植到裸鼠后,经过移植后1、3及22周不同时间段的观察,卵泡能够存活,并且发育到窦卵泡阶段。     

腹腔镜下卵巢子宫内膜异位囊肿剔除对患者卵巢储备功能的影响研究

目的探讨腹腔镜下卵巢子宫内膜异位囊肿剔除对患者卵巢储备功能的影响。方法选择2013年3月~2014年9月于我院就诊收治并确诊为卵巢子宫内膜异位囊肿60例患者,随机分为两组,包括观察组35例应用腹腔镜下异位囊肿剔除,对照组25例进行开腹剔除,观察记录不同组患者在术前末次月经第3天、术后第1次月经第3天、术后6个月的月经第3天血清卵泡刺激素(FSH)、雌二醇(E2)、窦卵泡数(AFC)及抗苗勒式氏管激素(AMH)的测定值,并作统计学分析。结果观察组患者在T1时间段测定的卵泡雌激素、雌二醇值较之对照组差异具有统计学意义(P0.05)。观察组患T1时间段的窦卵泡计数和抗苗勒氏管激素测定值较之对照组差异明显,具有统计学意义(P0.05)。结论腹腔镜卵巢子宫内膜异位囊肿切除术仅在行使手术后近时间段内对卵巢储备功能的影响较为突出,后期影响同开腹剥除效果类同。     

八珍益母丸对更年期雌性大鼠卵巢、子宫及激素的影响

目的探讨八珍益母丸对更年期雌性大鼠卵巢、子宫及激素的影响。方法建立更年期大鼠模型,观察口服八珍益母丸后更年期雌性大鼠卵巢、子宫指数及血清雌激素(E2)、促黄体生成激素(LH)、促卵泡激素(FSH)、孕激素(P)4项激素水平的变化。结果八珍益母丸组可显著提高子宫、血清E2和P 2项激素水平。结论八珍益母丸具有增加更年期雌性大鼠子宫指数、血清E2和P激素水平的作用。     

卵巢子宫内膜异位囊肿腹腔镜手术对卵巢储备功能影响的研究

目的探讨卵巢子宫内膜异位囊肿腹腔镜手术治疗对卵巢储备功能的影响。方法选择2008年6月～2010年6月住院的卵巢子宫内膜异位囊肿实行腹腔镜手术的患者80例,其中单侧卵巢子宫内膜异位囊肿37例患者作为A组;双侧卵巢子宫内膜异位囊肿43例患者作为B组。选择单侧卵巢畸胎瘤腹腔镜手术患者35例为对照组,比较各组手术前后血清黄体生成激素、雌二醇、卵泡刺激素的变化,随访患者术后6个月及术后1年基础FSH的恢复情况。结果与患者术前血清激素水平比较,术后B组卵泡刺激素明显增高,雌二醇明显下降,黄体生成激素明显下降,差异有统计学意义(P<0.05)。与患者术前血清激素水平比较,A组和对照组术后各激素水平差异均无统计学意义。术后,与对照组比较,B组卵泡刺激素明显增高,雌二醇明显下降,黄体生成激素明显下降,差异有统计学意义(P<0.05)。结论腹腔镜手术对双侧卵巢子宫内膜异位囊肿的卵巢储备功能有一定影响。     

米非司酮对大鼠异位子宫内膜超微结构影响

目的 :探讨米非司酮对大鼠异位子宫内膜作用及超微结构影响。方法:建立WistarII级雌性大鼠子宫内膜异位症模型 ,实验组给予10(A组 ) ,25(B组 ) ,50(C组 )mg/(kg·d)米非司酮灌胃 ,对照组只给等量水灌胃 ,4周后处死动物。取异位结节、在位子宫进行病理学及超微病理学研究 ,取血测定雌激素、孕激素、皮质醇。结果:电镜下腺上皮微绒毛有处脱失而呈扁平状 ,整个细胞呈暗调 ,管腔内可见蛋白质分泌物 ,平滑肌细胞核淡染。血清雌、孕激素水平与对照组差别无统计学意义(P>0.05) ;C组血清皮质醇水平减低 ,与对照组差别有统计学意义(P<0.05) ,A组、B组与对照组相比差别无统计学意义(P>0.05)。结论:非米司酮可明显抑制大鼠异位内膜上皮及腺体 ,间质透明变性 ;影响到异位内膜结构。米非司酮对雌孕激素影响不明显。     

围绝经期功能失调性子宫出血治疗现状

围绝经期功能失调性子宫出血（以下简称为围绝经期功血）是绝经过渡期妇女下丘脑-垂体-卵巢轴系统的神经内分泌调节机制失常所致的异常子宫出血,而无全身及内外生殖器官引起子宫出血的器质性病变存在,占功能失调性子宫出血发病的50%.在绝经过渡期,卵巢功能不断衰退,卵巢对垂体促性腺激素的反应低下,卵泡发育受阻而不能排卵,导致子宫内膜受单一雌激素刺激且无孕激素对抗而发生雌激素突破性出血或撤退性出血.主要表现为月经过多,子宫不规则过多出血.     

地屈孕酮在卵巢子宫内膜异位囊肿相关性不孕患者术后管理中的效果

目的 观察地屈孕酮在卵巢子宫内膜异位囊肿相关性不孕患者术后管理中的效果。方法 回顾性选取2020年9月—2021年11月泉州市妇幼保健院·儿童医院收治的卵巢子宫内膜异位囊肿相关性不孕患者60例,按照术后用药不同分为观察组和对照组,各30例。腹腔镜下卵巢子宫内膜异位囊肿剥除术后予以生育指导,观察组于月经第5～25天予地屈孕酮至确认妊娠或术后1年;对照组术后月经来潮第1天予亮丙瑞林,后期待自然妊娠至术后1年。观察2组患者术后月经、排卵情况,术前与术后1、3个月类绝经症状评分及血清糖类抗原125(CA125)、抗缪勒氏管激素(AMH)、血管内皮生长因子(VEGF)水平,术后随访1年的临床妊娠率和复发率。结果 观察组术后月经规律,行阴道彩超监测卵泡可见卵泡发育良好且有排卵;对照组用药期间出现闭经,平均(116.3±15.4)d,停药后月经规律,阴道彩超监测卵泡可见卵泡发育良好且有排卵。观察组手术前后改良Kupperman评分比较差异无统计学意义(P>0.05),对照组术后1、3个月改良Kupperman评分均高于手术前及同期观察组(P<0.01);术后1、3个月,2组血清CA125...     

Predominant role of the hypothalamic–pituitary axis,not the ovary,in different types of abnormal cycle induction by postnatal exposure to high dose p-tert-octylphenol in rats

To determine whether it is the hypothalamic–pituitary axis or the ovary that plays the predominant role in abnormal estrous cycling induction by postnatal exposure to estrogenic compounds, female rats were subcutaneously injected with 100 mg/kg p-tert-octylphenol or vehicle for 5 or 15 days after birth (OP-PND5, OP-PND15 or control). Ovaries were exchanged between control and treated groups on PND28. Controls receiving control or OP-PND5 ovaries showed normal cycles within 4 weeks after the exchange, and corpora lutea were detected in transplanted ovaries. Controls receiving OP-PND15 ovaries consistently increased persistent estrus (PE). OP-PND15 rats receiving control or OP-PND15 ovaries immediately descended into PE, and transplanted ovaries were atrophic with cystic follicles, indicating anovulation. OP-PND5 rats receiving control or OP-PND5 ovaries showed early onset of PE after normal cycling. The hypothalamic–pituitary axis is predominant in abnormal cycling induction by postnatal exposure to OP. OP-PND15 ovaries were impaired compared to other groups.     

Gonadal toxicity of an ethanol extract of Psoralea corylifolia in a rat 90-day repeated dose study

Ethanol extracts of seeds of Psoralea corylifolia are proposed as food additives for processed food preservation. An extract was administered by admixing into diet at concentrations of 0, 0.375, 0.75, 1.5 or 3.0% to 10 male and 10 female F344 rats each for 90 days to evaluate its toxicity. Body weight gain, food consumption and food conversion efficiency (body weight gain per food consumption) were lower in the extract-treated animals, except for the 0.375% males, as compared to the control animals. Absolute and/or relative testes weights in the 1.5 and 3.0% groups and those of ovaries in the 3.0% group were significantly (p < 0.01) lower than in the control group. On histopathological examination, seminiferous tubular atrophy and Leydig cell atrophy in the testes, and epithelial cell atrophy in the seminal vesicles and prostate were observed in the 1.5 and 3.0% males. Decrease in the number of corpora lutea associated with frequent necrotic follicles in the ovaries in the 1.5 and 3.0% females and less frequent endometrial glands in the uterus in the 3.0% females were also detected. These results might suggest disruption of the hypothalamus-pituitary-gonadal axis in Psoralea corylifolia-treated rats as possible mechanisms underlying this gonadal toxicity.     

Involvement of gonadotropins in the induction of hypertrophy-hyperplasia in the interstitial tissues of ovaries in neonatally diethylstilbestrol-treated mice

Neonatally diethylstilbestrol (DES) treatment causes hypertrophy-hyperplasia in the interstitial tissue of mouse ovaries. To understand the induction mechanism of the hypertrophy, mRNA expression involved in steroidogenesis in the ovary of neonatally DES-treated mice was examined. The expression of StAR and Cyp11a1 was significantly reduced while Cyp19 and Sf-1 were stimulated in the ovary of neonatally DES-treated 3-month-old mice. Expression of those genes was not different between DES- and oil-treated mice after the gonadotropins treatment. Lhb in the pituitary of 3-month-old neonatally DES-treated mice was significantly decreased. Finally, ovaries from DES-treated mice transplanted to neonatally oil-treated hosts had developing follicles at several stages and corpora lutea, whereas grafted ovaries from neonatally oil-treated mice in 3-month-old neonatally DES-treated hosts showed lipid accumulation in the interstitial tissue. Thus, hypertrophy and accumulation of lipid droplets in interstitial cells of neonatally DES-treated mice is caused by impaired steroidogenesis due to the alterations of gonadotropins levels.     

Effect of triptolide on reproduction of female lesser bandicoot rat,Bandicota bengalensis

Abstract

Triptolide has been reported to cause antifertility in male rats and mice. However, studies on female rats have been limited. Present study was aimed to evaluate the effects of triptolide on reproduction of wild female rodent pest species, Bandicota bengalensis. Feeding of bait containing 0.1, 0.15 and 0.2% triptolide for a period of 15 days in bi-choice resulted in per day ingestion of 17.37, 23.54 and 27.49?mg/kg body weight of triptolide, respectively. Examination of vaginal smear of all the rats revealed a significant (p?≤?0.05) increase in duration of estrous cycle due to increase in durations of metestrous and diestrous stages in rats of treated groups. Autopsy of rats after 15 and 30 days of treatment withdrawal revealed significant (p?≤?0.05) reduction in weights of uterus and ovaries, non-significant reduction in weights of liver and levels of estradiol and progesterone and significant (p?≤?0.05) reduction in levels of urea and BUN and increase in levels of plasma proteins, ALT, AST, ALP, ACP and LDH in rats of treated groups compared to untreated group. There was no significant (p?≤?0.05) effect of treatment on body weight. Triptolide treatment affected the histomorphology of uterus by causing a decrease in lumen and columnar cell height and number of uterine glands and ovary by increasing the number of atretic follicles and decreasing the number of developing follicles. The present study suggests triptolide to be a strong candidate affecting reproduction of female B. bengalensis.     

Triptolide induces adverse effect on reproductive parameters of female Sprague-Dawley rats

The aim of this study was to investigate the adverse effects of triptolide, a diterpenoid triepoxid and a major active component isolated from Triptergium wilfordii Hook.f (TWHF), on various reproductive parameters of female Sprague-Dawley (SD) rats. Female SD rats were treated with triptolide by oral administration (gastric infusion; 0, 100, 200, and 400 μg/kg) once-daily for 90 days. During the experimental period, vaginal smears were taken to monitor the estrous phase for the last 30 days. Relative ovary and uterus weights to body and histopathologically changes were determined on the last day. Serum levels of estradiol (E(2)), progesterone (P), follicle-stimulating hormone (FSH), and luteotropic hormone (LH) were assessed by enzyme immunoassay. ERα expression in the uterus and ovaries were analyzed from using immunohistochemical detection. The results showed that treatment with 200 and 400 ug/kg of triptolide significantly reduced serum levels of E(2) and P and increased levels of FSH and LH. At these dose levels, relative weights of ovary and uterus were significantly reduced. Qualitative histological analysis of the ovaries revealed a reduction in developing follicles and increase in atretic follicles in treated animals. Further, estrous cycles were prolonged significantly. The expression of ERα in ovaries and the uterus decreased in treated animals. These data suggest that triptolide had a direct effect on the ovaries, and the decrease in steroids elicited feedback on FSH and LH. Thus, reduced levels of E(2) and P may affect follicular development, estrous cycle, and expression of ERα.     

An etheral extract of Kamala (Mallotus philippinensis (Moll.Arg) Lam.) seed induce adverse effects on reproductive parameters of female rats

The present study was designed to investigate the adverse effects of indigenous Kamala seed etheral extract on various reproductive parameters of female rats. Animals were treated with various doses (50, 75 and 100 mg/kg body weight, (bw)) of seed extract through gavage for 30 days. Treatment with a higher dose of seed extract (100mg/kg bw) significantly reduced serum levels of FSH, LH and estradiol. At this dose level, relative weights of ovary and uterus was significantly reduced, whereas lower doses (75 and 50 mg/kg bw) did not show any untoward effect. Qualitative analysis regarding histology of ovary revealed reduction in the developing follicles and an increase in the atretic follicles in treated animals as compared to the untreated. Kamala seed extract-induced follicular atresia was further supported by immunoblot/densitometry analysis that ovarian lysate from treated animal had 2.5 times more bax protein expression compared to control ovaries. The number of ovulated eggs and corpora lutea per animal were reduced significantly. Similarly, higher doses of seed extract reduced number of oestrous cycle, whereas the length of cycle was increased significantly. The oestrous and proestrous phases were reduced, while metestrous and diestrous phases were significantly increased. When the females treated with Kamala seed extract were mated with non-treated males, rate of infertile mating increased in a dose-dependent manner with reduced pregnancy rate and number of implantation sites. Taken together, these data indicate that Kamala reduced serum FSH and LH levels probably by affecting hypothalamic/pituitary axis in treated animals. Thus, reduced levels of FSH and LH and estradiol might have affected the follicular development, quality and number of ovulated eggs, corpora lutea formation, oestrous cycle, establishment and maintenance of pregnancy in treated rats.     

Deciduoma formation in rats treated neonatally with the anti-estrogens, tamoxifen and MER-25

Female rats of the T strain were given single daily injections of 100 micrograms and 200 micrograms of tamoxifen (Tx) and MER-25 (MER) for 5 days beginning on the day of birth (DAY 1). When sacrificed on Day 60, the Tx-treated rats (Tx rats) exhibited continued vaginal diestrus, whereas the females given MER or the vehicle alone showed regular estrous cycles. Ovaries from Tx rats were polyfollicular without corpora lutea, while those from MER rats, as well as from the controls given the vehicle alone, invariably contained both follicles and corpora lutea. In Tx rats, the uteri underwent atrophy, containing few uterine glands in an endometrium largely occupied by fibroblasts. Decidual response of the uterus to intraluminal oil instillation was markedly reduced in Tx rats given an appropriate regimen of progesterone and estradiol injections following ovariectomy on Day 60. By contrast, MER given neonatally had little effects on decidualization. Since ovariectomy on Day 10 brought about no amelioration of the decidualization in Tx rats, it is suggested that the lowered deciduogenic responsiveness to the instillation was caused by a direct action of Tx on the uterus of neonatal rats rather than by a Tx-induced alteration of hypothalamo-hypophyseal-ovarian system. Differences in effect on the female reproductive system between Tx and MER were discussed.     

Evaluation of ovarian toxicity of mono-(2-ethylhexyl) phthalate (MEHP) using cultured rat ovarian follicles

Mono-(2-ethylhexyl) phthalate (MEHP) is the most toxic metabolite of di-(2-ethylhexyl) phthalate (DEHP). It has been reported that DEHP causes abnormal reproductive development in women, and suppresses estradiol synthesis and ovulation in female rats with diminished size of preovulatory follicles. The present study was conducted to evaluate the ovarian toxicity of MEHP using cultured rat ovarian follicles. Secondary follicles were isolated from the ovaries of 14-day-old female rats and cultured for 48 hr with MEHP (0, 10, 30, and 100 μg/ml). At 0, 24, and 48 hr of MEHP treatment, follicular diameters were measured. After the culture, viability and apoptosis of follicles were assessed, and progesterone, androstenedione, testosterone, and estradiol levels in culture media were measured. At 100 μg/ml, suppression of follicular development was observed, which is associated with decreased viability of follicles and apoptosis of granulosa cells. At this concentration, progesterone level increased markedly, whereas androstenedione, testosterone, and estradiol levels decreased. At 10 and 30 μg/ml, follicular development was not suppressed, no apoptotic change was observed, and the levels of all measured steroid hormones tended to increase. The combined levels of all steroid hormones increased at all concentrations of MEHP, and the increase implies that MEHP activates the synthetic pathway from cholesterol to estradiol including de novo synthesis of cholesterol. However, the progesterone/androstenedione ratio increased extremely at 100 μg/ml, and the increase implies that MEHP inhibits the conversion of progesterone to androstenedione. In conclusion, MEHP induces ovarian toxicity via suppression of follicular development and abnormal steroid hormone synthesis in cultured rat ovarian follicles.     

Evaluation of ovarian toxicity of sodium valproate (VPA) using cultured rat ovarian follicles

Sodium valproate (VPA) is a major antiepileptic drug that is widely used for the treatment of epilepsy as well as other neuropsychiatric diseases. The present study was conducted to evaluate the ovarian toxicity of VPA using cultured rat ovarian follicles. Secondary follicles were isolated from the ovaries of 14-day-old female rats and cultured for 48 hr with VPA (0, 0.2, 1.0, and 5.0 mM). At 0, 24, and 48 hr of VPA treatment, follicular diameters were measured. After the culture, viability of follicles and expression of aromatase in the follicles were assessed, and progesterone, androstenedione, testosterone, and estradiol levels in culture media were measured. At all concentrations of VPA, follicular development was suppressed, and androstenedione, testosterone, estradiol, and combined levels of all steroid hormones tended to decrease in association with suppression of aromatase expression in granulosa cells. Additionally, the suppression of follicular development was associated with decreased viability of follicles and an increased progesterone level at 5.0 mM of VPA. The decrease in the combined levels of all steroid hormones implies that VPA suppresses the synthetic pathway from cholesterol to estradiol including de novo synthesis of cholesterol. In conclusion, VPA induces ovarian toxicity via suppression of development and abnormal steroid hormone synthesis in cultured rat ovarian follicles.