Fetal programming: testosterone exposure of the female sheep during midgestation disrupts the dynamics of its adult gonadotropin secretion during the periovulatory period.
Fetal programming: testosterone exposure of the female sheep during midgestation disrupts the dynamics of its adult gonadotropin secretion during the periovulatory period.
复制标题
胎儿编程：雌性绵羊在妊娠中期暴露的睾酮会扰乱其在排卵期期间成年促性腺激素分泌的动态。
DOI：
10.1095/biolreprod.104.031070
复制
发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Padmanabhan,Vasantha
中科院分区：
文献类型：
--
作者：
Savabieasfahani,Mozhgan;Lee,JamesS;Herkimer,Carol;Sharma,TejinderP;Foster,DouglasL;Padmanabhan,Vasantha
母羊产前暴露于过量的睾酮（T）会导致高促性腺激素，多卵泡卵巢和生殖周期的进行性丧失。我们已经确定，产前T治疗延迟雌二醇（E2）诱导的LH峰的潜伏期。为了将这一发现扩展到自然生理环境中，本研究旨在确定程序错误的浪涌机制是否会改变生殖周期。具体来说，我们希望确定产前T治疗是否1）延迟排卵前促性腺激素峰在自然卵泡期E2升高期间的开始，2）改变LH的脉动分泌和继发性FSH峰的动力学，3）损害随后的黄体功能。对妊娠第60天至第90天（足月147天）接受产前T给药的雌性动物和对照雌性动物（约2.5岁）进行了研究。对照组和产前T给药组雌性动物的生殖周期与PGF 2 α同步，每2小时采集一次外周血样本，持续120小时，以表征E2、LH和FSH的周期变化，然后每天采集一次，持续14天，以监测黄体孕酮的变化。为了评估LH脉冲模式，还在周期的卵泡期和黄体期频繁采集血液样本（每5分钟采集一次，共6小时）。结果表明，产前T处理的雌鼠，排卵前E_2升高正常，排卵前E_2升高与LH、FSH峰峰值之间的时间间隔较长，但幅度相似，卵泡期LH脉冲频率增加，FSH峰峰值与排卵前E_2升高之间的时间间隔较长，但幅度相似，排卵前E_2升高与LH、FSH峰峰值之间的时间间隔较长。（4）第一次和第二次FSH峰之间的时间间隔缩短，但第二次FSH峰的持续时间有增加的趋势;（5）黄体孕酮模式一般不变。因此，女性在出生前暴露于过量的T会引起排卵期促性腺激素分泌动力学的紊乱和不定时，但这些不会引起周期规律性或黄体功能的明显缺陷。为了揭示导致妊娠中期过量T暴露引起的最终生育力低下的病理学，必须在较大年龄进行研究，以评估是否存在神经内分泌和卵巢功能的进行性破坏。
Prenatal exposure of the female sheep to excess testosterone (T) leads to hypergonadotropism, multifollicular ovaries, and progressive loss of reproductive cycles. We have determined that prenatal T treatment delays the latency of the estradiol (E2)-induced LH surge. To extend this finding into a natural physiological context, the present study was conducted to determine if the malprogrammed surge mechanism alters the reproductive cycle. Specifically, we wished to determine if prenatal T treatment 1) delays the onset of the preovulatory gonadotropin surge during the natural follicular phase rise in E2, 2) alters pulsatile LH secretion and the dynamics of the secondary FSH surge, and 3) compromises the ensuing luteal function. Females prenatally T-treated from Day 60 to Day 90 of gestation (147 days is term) and control females were studied when they were ∼2.5 yr of age. Reproductive cycles of control and prenatally T-treated females were synchronized with PGF2α, and peripheral blood samples were collected every 2 h for 120 h to characterize cyclic changes in E2, LH, and FSH and then daily for 14 days to monitor changes in luteal progesterone. To assess LH pulse patterns, blood samples were also collected frequently (each 5 min for 6 h) during the follicular and luteal phases of the cycle. The results revealed that, in prenatally T-treated females, 1) the preovulatory increase in E2was normal; 2) the latencies between the preovulatory increase in E2and the peaks of the primary LH and FSH surges were longer, but the magnitudes similar; 3) follicular-phase LH pulse frequency was increased; 4) the interval between the primary and secondary FSH surges was reduced but there was a tendency for an increase in duration of the secondary FSH surge; but 5) luteal progesterone patterns were in general unaltered. Thus, exposure of the female to excess T before birth produces perturbances and maltiming in periovulatory gonadotropin secretory dynamics, but these do not produce apparent defects in cycle regularity or luteal function. To reveal the pathologies that lead to the eventual subfertility arising from excess T exposure during midgestation, studies at older ages must be conducted to assess if there is progressive disruption of neuroendocrine and ovarian function.