Engelbregt M J T, van Weissenbruch M M, Popp-Snijders C, Delemarre-van de Waal H A
Department of Clinical Chemistry and Endocrinology, Research Institute for Endocrinology, Reproduction and Metabolism, VU Medical Center, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
J Endocrinol. 2002 May;173(2):297-304. doi: 10.1677/joe.0.1730297.
In the present study we examined the consequences of intrauterine growth retardation and postnatal food restriction on the maturational process of sexual development by studying onset of first cycle. In addition, we investigated the effect of pregnant mare serum gonadotropin (PMSG) on ovarian growth and ovulation in intrauterine growth-retarded (IUGR) and postnatally food-restricted (PFR) rats. Intrauterine growth retardation was induced by uterine artery ligation on day 17 of gestation and food restriction was achieved by enlarging the litter to 20 pups per mother from day 2 after birth until weaning (day 24). In control rats, vaginal opening and the first cycle took place on the same day. In IUGR rats, uncoupling occurred between vaginal opening and the first cycle. Vaginal opening was delayed (P<0.05) and the first cycle was even further delayed (P<0.01) compared with controls. Body weight in IUGR rats was lower (P<0.05) at vaginal opening, but at first cycle and after stimulation with 50 IU PMSG in the first cycle it was similar to that in controls. In the ovaries of IUGR rats, the numbers of primordial (P<0.05), growing (P<0.01) and antral follicles (P<0.01), and the total number of follicles (P<0.01) were lower than in controls after stimulation with 50 IU PMSG at first cycle. The number of corpora lutea in the ovaries of the IUGR rats and the controls was similar and reflected superovulation. In the PFR rats, vaginal opening occurred at the same time as in control rats, but at a lower body weight (P<0.01). First cycle was much delayed (P<0.01), by which time body weight was greater (P<0.01) than that of controls at first cycle. On the basis of the differences in weight and age between PFR rats and controls at first cycle, we performed two studies. In study A, ovaries were analysed histologically 42 h after stimulation with PMSG at first cycle of control rats and age-matched PFR rats. In study B, the ovaries of PFR rats at first cycle and age-matched control rats were examined 42 h after PMSG stimulation. In the ovaries of the PFR rats in study A, a greater total number of follicles (P<0.05) was observed, represented by a greater number of primordial follicles (P<0.01) and a lower number of antral follicles (P<0.05), including corpora lutea. The number of corpora lutea in the ovaries of the PFR rats was significantly lower than that in controls (P<0.01). The total number of follicles in the ovaries of the PFR rats of study B did not differ from the age-matched controls after PMSG stimulation at first cycle, and neither did the number of the follicles in the different classes. We conclude that, in IUGR rats at first cycle, PMSG can induce multiple follicular growth and development followed by superovulation comparable to that in controls, despite a decreased total number of follicles in the ovaries. However, in PFR rats of the same age, the ovary is not capable of responding adequately to PMSG, despite a greater total number of follicles. Stimulation with PMSG at first cycle resulted in follicular growth and superovulation comparable to those in age-matched controls. Undernutrition in different critical time periods around birth in the rat leads to ovarian development in such a way that, in both groups, an increased risk of reduced reproductive capacity can be expected.
在本研究中,我们通过研究首次发情周期的开始情况,来探究宫内生长受限和出生后食物限制对性发育成熟过程的影响。此外,我们还研究了孕马血清促性腺激素(PMSG)对宫内生长受限(IUGR)和出生后食物受限(PFR)大鼠卵巢生长和排卵的影响。宫内生长受限通过在妊娠第17天结扎子宫动脉诱导产生,食物限制则通过从出生后第2天至断奶(第24天)将每只母鼠的窝仔数增加到20只来实现。在对照大鼠中,阴道开口和首次发情周期在同一天发生。在IUGR大鼠中,阴道开口和首次发情周期出现了分离。与对照组相比,阴道开口延迟(P<0.05),首次发情周期甚至进一步延迟(P<0.01)。IUGR大鼠在阴道开口时体重较低(P<0.05),但在首次发情周期时以及在首次发情周期用50 IU PMSG刺激后,其体重与对照组相似。在IUGR大鼠的卵巢中,首次发情周期用50 IU PMSG刺激后,原始卵泡(P<0.05)、生长卵泡(P<0.01)和窦状卵泡(P<0.01)的数量以及卵泡总数(P<0.01)均低于对照组。IUGR大鼠和对照组卵巢中的黄体数量相似,均反映了超排卵情况。在PFR大鼠中,阴道开口与对照大鼠同时发生,但体重较低(P<0.01)。首次发情周期延迟很多(P<0.01),此时体重比对照组首次发情周期时更大(P<0.01)。基于PFR大鼠和对照组在首次发情周期时体重和年龄的差异,我们进行了两项研究。在研究A中,在对照大鼠和年龄匹配的PFR大鼠首次发情周期用PMSG刺激42小时后,对卵巢进行组织学分析。在研究B中,在PMSG刺激42小时后,检查PFR大鼠首次发情周期时的卵巢和年龄匹配的对照大鼠的卵巢。在研究A中PFR大鼠的卵巢中,观察到卵泡总数更多(P<0.05),表现为原始卵泡数量更多(P<0.01),窦状卵泡数量更少(P<0.05),包括黄体。PFR大鼠卵巢中的黄体数量显著低于对照组(P<0.01)。研究B中PFR大鼠首次发情周期用PMSG刺激后,其卵巢中的卵泡总数与年龄匹配的对照组无差异,不同类型卵泡的数量也无差异。我们得出结论,在IUGR大鼠首次发情周期时,尽管卵巢中卵泡总数减少,但PMSG仍可诱导多个卵泡生长发育,随后出现与对照组相当的超排卵情况。然而,在相同年龄的PFR大鼠中,尽管卵泡总数更多,但卵巢对PMSG的反应能力不足。首次发情周期用PMSG刺激导致卵泡生长和超排卵与年龄匹配的对照组相当。大鼠出生前后不同关键时期的营养不良导致卵巢发育异常,在两组中都可能预期生殖能力下降的风险增加。