Hormone-induced delayed ovulation affects early embryonic development

Bittner, Ann‐Kathrin; Horsthemke, Bernhard; Winterhager, Elke; Grümmer, Ruth

doi:10.1016/j.fertnstert.2011.03.022

Cited by 16 publications

(21 citation statements)

References 28 publications

(32 reference statements)

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“…For example, supraphysiologic E 2 levels have been shown to have a toxic effect on the developing embryo in mice, leading to impairment in embryonic adhesion and implantation potential [19][20][21]. Elevated estrogen levels also impair the expression of implantation-associated genes in mice, leading to aberrant placentation [22].…”

Section: Discussionmentioning

confidence: 99%

Impact of elevated peak serum estradiol levels during controlled ovarian hyperstimulation on the birth weight of term singletons from fresh IVF-ET cycles

Pereira

Reichman

Goldschlag

et al. 2015

J Assist Reprod Genet

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Purpose To investigate the impact of elevated serum estradiol (E 2 ) levels on the day of hCG trigger on the birth weight of term singletons after fresh In Vitro Fertilization (IVF)-Embryo Transfer (ET) cycles. Methods Retrospective cohort study of all patients initiating fresh IVF-ET cycles resulting in live births between January 2004 and February 2013. The incidence of low birthweight (LBW) term singletons in patients with E 2 levels on day of hCG trigger above or below the 95 % cutoff for E 2 values in our clinic (3,069.2 pg/mL) was estimated. Multiple gestations and vanishing twin pregnancies were excluded. Results Two thousand nine hundred thirty-nine singleton live births were identified for inclusion. One hundred forty seven (5 %) and 2792 (95 %) live singleton births occurred in patients with peak E 2 levels above and below 3,069.2 pg/mL, respectively. The overall incidence of term LBW was 5.4 % in the >3,069.2 pg/mL group compared to 2.4 % in the ≤3,069.2 pg/mL group (P=.038). An E 2 level >3,069.2 pg/mL on the day of hCG administration was associated with increased odds of LBW term singletons (OR=2.29; 95 % CI=1.03-5.11). The increased odds remained unchanged when adjusting for maternal age (aOR=2.29; 95 % CI=1.02-5.14; P=.037), gestational age at delivery (aOR=2.04; 95 % CI=1.22-3.98; P=.025), and day 3 versus blastocyst transfer (aOR=2.5; 95 % CI=1.11-5.64; P=.023).Conclusions Peak E 2 level >3,069.2 pg/mL is associated with increased odds of LBW term singletons after fresh IVF-ET cycles. Conservative stimulation protocols aiming not to exceed an E 2 level of 3,000 pg/mL may be advantageous for placentation and fetal growth if a fresh transfer is planned.

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Section: Discussionmentioning

confidence: 99%

Impact of elevated peak serum estradiol levels during controlled ovarian hyperstimulation on the birth weight of term singletons from fresh IVF-ET cycles

Pereira

Reichman

Goldschlag

et al. 2015

J Assist Reprod Genet

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“…To achieve prolonged follicle growth and oogenesis in vivo , ovulation was delayed in superovulated 4-6 week old C57Bl/6J female mice by application of the GnRH antagonist cetrorelix (Cetrotide, Merck-Serono), as described previously [2,11]. In short, mice were stimulated by intraperitoneal injection of 10 IU pregnant mare serum gonadotropin (PMSG; Intergonan, MSD) to induce follicle growth.…”

Section: Methodsmentioning

confidence: 99%

“…Even though preovulatory aging is known to reduce oocyte quality and can cause developmental defects in the embryo in many different animal models, such as frogs, fish, urodeles, guinea pigs and rats [1], little is known about the underlying molecular mechanisms. Recently, an in vivo mouse model was established to investigate preovulatory aging in more detail [2]. In this model, ovulation was postponed by application of the gonadotropin releasing hormone (GnRH) antagonist cetrorelix, resulting in decreased embryo weight and increased embryo resorption [2].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, an in vivo mouse model was established to investigate preovulatory aging in more detail [2]. In this model, ovulation was postponed by application of the gonadotropin releasing hormone (GnRH) antagonist cetrorelix, resulting in decreased embryo weight and increased embryo resorption [2]. Preovulatory aging may also occur during in vitro oocyte growth and maturation in follicle cultures.…”

Section: Introductionmentioning

confidence: 99%

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Preovulatory Aging In Vivo and In Vitro Affects Maturation Rates, Abundance of Selected Proteins, Histone Methylation Pattern and Spindle Integrity in Murine Oocytes

et al. 2016

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Delayed ovulation and delayed fertilization can lead to reduced developmental competence of the oocyte. In contrast to the consequences of postovulatory aging of the oocyte, hardly anything is known about the molecular processes occurring during oocyte maturation if ovulation is delayed (preovulatory aging). We investigated several aspects of oocyte maturation in two models of preovulatory aging: an in vitro follicle culture and an in vivo mouse model in which ovulation was postponed using the GnRH antagonist cetrorelix. Both models showed significantly reduced oocyte maturation rates after aging. Furthermore, in vitro preovulatory aging deregulated the protein abundance of the maternal effect genes Smarca4 and Nlrp5, decreased the levels of histone H3K9 trimethylation and caused major deterioration of chromosome alignment and spindle conformation. Protein abundance of YBX2, an important regulator of mRNA stability, storage and recruitment in the oocyte, was not affected by in vitro aging. In contrast, in vivo preovulatory aging led to reduction in Ybx2 transcript and YBX2 protein abundance. Taken together, preovulatory aging seems to affect various processes in the oocyte, which could explain the low maturation rates and the previously described failures in fertilization and embryonic development.

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“…E2 (250 ng dissolved in 0.1 mL of peanut oil; Sigma-Aldrich Co., St Louis, MO) and/or P (2 mg dissolved in 0.1 mL of peanut oil; Sigma-Aldrich Co.) were administered subcutaneously to some of the OVX mice, at 1,000 h for five consecutive days [9,10]. Three days before sampling, the GnRH antagonist cetrorelix (10 µg in 0.2 mL saline/daily, S.C.; Cetrotide, Merck KGaA, Darmstadt, Germany) was administered subcutaneously to some of the OVX mice, at 1,000 h for three consecutive days [11]. Six days after ovariectomy, the mice were decapitated between 1,000 and 1,200 h, and their pituitary glands and uteri were collected for RNA extraction and wet weight measurements, respectively.…”

Section: Ovariectomy and Hormonal Replacementmentioning

confidence: 99%

Effects of ovarian hormones on GPR120 mRNA expression in mouse pituitary gonadotrophs

2017

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Hormone-induced delayed ovulation affects early embryonic development

Cited by 16 publications

References 28 publications

Impact of elevated peak serum estradiol levels during controlled ovarian hyperstimulation on the birth weight of term singletons from fresh IVF-ET cycles

Impact of elevated peak serum estradiol levels during controlled ovarian hyperstimulation on the birth weight of term singletons from fresh IVF-ET cycles

Preovulatory Aging In Vivo and In Vitro Affects Maturation Rates, Abundance of Selected Proteins, Histone Methylation Pattern and Spindle Integrity in Murine Oocytes

Effects of ovarian hormones on GPR120 mRNA expression in mouse pituitary gonadotrophs

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