Octopamine is required for successful reproduction in the classical insect model, Rhodnius prolixus.

In insects, biogenic amines function as neurotransmitters, neuromodulators, and neurohormones, influencing various behaviors, including those related to reproduction such as response to sex pheromones, oogenesis, oviposition, courtship, and mating. Octopamine (OA), an analog of the vertebrate norepinephrine, is synthesized from the biogenic amine tyramine by the enzyme tyramine ß-hydroxylase (TßH). Here, we investigate the mechanisms and target genes underlying the role of OA in successful reproduction in females of Rhodnius prolixus, a vector of Chagas disease, by downregulating TßH mRNA expression (thereby reducing OA content) using RNA interference (RNAi), and in vivo and ex vivo application of OA. Injection of females with dsTßH impairs successful reproduction at least in part, by decreasing the transcript expression of enzymes involved in juvenile hormone biosynthesis, the primary hormone for oogenesis in R. prolixus, thereby interfering with oogenesis, ovulation and oviposition. This study offers valuable insights into the involvement of OA for successful reproduction in R. prolixus females. Understanding the reproductive biology of R. prolixus is crucial in a medical context for controlling the spread of the disease.

[Effect of acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28) on PI3K/AKT/FOXO3a pathway in mice with poor ovarian response].

OBJECTIVE: To observe the protective effect of acupuncture at "Zhibian" (BL 54) through "Shuidao (ST 28)" based on the PI3K/AKT/FOXO3a pathway in mice with poor ovarian response (POR), and to explore the possible mechanism of acupuncture in inhibiting ovarian granulosa cells apoptosis in POR. METHODS: A total of 45 mice with regular estrous cycles were randomly divided into a blank group, a model group and an acupuncture group, with 15 mice in each group. Mice in the model group and the acupuncture group were given triptolide suspension (50 mg•kg-1•d-1) by gavage for 2 weeks to establish POR model. After successful modeling, mice in the acupuncture group were given acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28) for 2 weeks, once a day, 20 min each time. Ovulation induction was started the day after the intervention ended, and samples were taken from each group after ovulation induction. Vaginal smears were used to observe changes in the estrous cycle of mice. The number of oocytes retrieved, ovarian wet weight, final body weight, and ovarian index were measured. The levels of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), estradiol (E2), and luteinizing hormone (LH) in serum were detected by ELISA. The morphology of ovarian tissue was observed by HE staining. The apoptosis of ovarian granulosa cells was detected by TUNEL staining. The mRNA expression of PI3K, AKT, and FOXO3a in ovarian tissue was detected by real-time fluorescence quantitative PCR. The protein expression of Bcl-2 associated X protein (BAX), caspase-3, phosphorylated phosphatidylinositol 3-kinase (p-PI3K), and phosphorylated protein kinase B (p-AKT) in ovarian tissue was detected by Western blot. RESULTS: Compared with the blank group, the rate of estrous cycle disorder in the model group was increased (P<0.01); compared with the model group, the rate of estrous cycle disorder in the acupuncture group was decreased (P<0.01). Compared with the blank group, the number of oocytes retrieved, ovarian wet weight, ovarian index, and final body weight in the model group were decreased (P<0.01); compared with the model group, the number of oocytes retrieved, ovarian index, and ovarian wet weight were increased (P<0.01, P<0.05), and there was no significant difference in final body weight (P>0.05) in the acupuncture group. Compared with the blank group, the serum levels of FSH and LH were increased (P<0.01), and the serum levels of AMH and E2 were decreased (P<0.01) in the model group; compared with the model group, the serum levels of FSH and LH were decreased (P<0.01, P<0.05), and the serum levels of AMH and E2 were increased (P<0.01, P<0.05) in the acupuncture group. Compared with the blank group, the number of normal developing follicles in ovarian tissue in the model group was decreased and the morphology was poor, while the number of atretic follicles increased; compared with the model group, the number, morphology, and granulosa cell structure of follicles in the acupuncture group improved to varying degrees, and the number of atretic follicles decreased. Compared with the blank group, the apoptosis rate of ovarian granulosa cells in the model group was increased (P<0.01); compared with the model group, the apoptosis rate of ovarian granulosa cells in the acupuncture group was decreased (P<0.01). Compared with the blank group, the FOXO3a mRNA expression and caspase-3 and BAX protein expression in ovarian tissue in the model group were increased (P<0.01), and the mRNA expression of PI3K and AKT and the protein expression of p-PI3K, p-AKT, and p-FOXO3a in ovarian tissue were decreased (P<0.01); compared with the model group, the mRNA expression of FOXO3a and protein expression of caspase-3 and BAX in ovarian tissue in the acupuncture group were decreased (P<0.05, P<0.01), and the mRNA expression of PI3K and AKT and the protein expression of p-PI3K, p-AKT, and p-FOXO3a in ovarian tissue were increased (P<0.01, P<0.05). CONCLUSION: Acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28) could inhibit ovarian cell apoptosis, and improve ovarian function in POR mice, and its mechanism may be related to the regulation of key factors in the PI3K/AKT/FOXO3a pathway.

Combined perceptual and chemical analyses show no compelling evidence for ovulatory cycle shifts in women's axillary odour.

Although men's attraction to women's body odour has been suggested to vary over the ovulatory cycle, peaking around the fertile window, we still lack methodologically robust evidence corroborating this effect. Further, the chemical underpinnings of male preference for the odour of ovulating women remain unknown. Here, we combined perceptual and chemical analyses to investigate the axillary odour of naturally cycling women over 10 days, covering the gradual change in fertility across the ovulatory cycle with a focus on fertile days. The fertile state was confirmed by urinary ovulation tests as well as salivary oestradiol and progesterone levels. Men rated the scent of unfamiliar women, resembling a first encounter. We used multivariate analyses to relate variation in both odour ratings and chemical composition to female conception probability, temporal distance to ovulation and ovarian hormone levels. Our results provide no evidence that males prefer the odour of fertile women. Furthermore, the volatile analysis indicated no link between axillary odour composition and current fertility status. Together, our results showed no convincing support for a chemical fertility cue in women's axillary odour, questioning the presence of olfactory fertility information that is recognizable during first encounters in modern humans.

In mares resistant to endometrial infection, periovulatory treatment with ecbolic drugs does not influence uterine clearance or luteal development.

We aimed to determine associations between experimentally impaired uterine clearance or treatment with ecbolic drugs on luteal development in estrous mares after insemination. In a crossover design, eight mares were treated with saline (CON), clenbuterol (CLEN), oxytocin (OXY) and carbetocin (CARB) from the day of first insemination until 2 days after ovulation. Between treatments, the mares rested for one cycle. Estrous mares were examined for the presence of free intrauterine fluid by transrectal ultrasound. Endometrial swabs for cytology and bacteriology were collected on days 1 and 14. Blood samples were collected daily before AI until day 14 after ovulation for determination of progesterone and PGF2α metabolites (PGFM). Differences between treatments were compared by a general linear model for repeated measures (SPSS 29). One mare was excluded because of a uterine infection in the control cycle. In all other mares, only minor amounts of free intrauterine fluid were present after insemination and decreased over time (P<0.05) with no treatment x time interaction. There was no effect of treatment on polymorphonucleated cells (PMN) in endometrial cytology after ovulation or PGFM secretion. Progesterone release from day 1-14 as well as pregnancy rate and conceptus size on day 14 was not influenced by treatment. In conclusion, treatment with clenbuterol does not impair uterine clearance in estrous mares resistant to endometritis. Repeated injection of the oxytocin analogue carbetocin during the early postovulatory period is not detrimental to corpus luteum function and can be recommended to enhance uterine clearance.

A double ovulation protocol for Xenopus laevis produces doubled fertilisation yield and moderately transiently elevated corticosterone levels without loss of egg quality.

The African claw-toed frog, Xenopus laevis, is a well-established laboratory model for the biology of vertebrate oogenesis, fertilisation, and development at embryonic, larval, and metamorphic stages. For ovulation, X. laevis females are usually injected with chorionic gonadotropin, whereupon they lay typically hundreds to thousands of eggs in a day. After being rested for a minimum of three months, animals are re-used. The literature suggests that adult females can lay much larger numbers of eggs in a short period. Here, we compared the standard "single ovulation" protocol with a "double ovulation" protocol, in which females were ovulated, then re-ovulated after seven days and then rested for three months before re-use. We quantified egg number, fertilisation rate (development to cleavage stage), and corticosterone secretion rate as a measure of stress response for the two protocol groups over seven 3-month cycles. We found no differences in egg number-per-ovulation or egg quality between the groups and no long-term changes in any measures over the 21-month trial period. Corticosterone secretion was elevated by ovulation, similarly for the single ovulation as for the first ovulation in the double-ovulation protocol, but more highly for the second ovulation (to a level comparable to that seen following shipment) in the latter. However, both groups exhibited the same baseline secretion rates by the time of the subsequent cycle. Double ovulation is thus transiently more stressful/demanding than single ovulation but within the levels routinely experienced by laboratory X. laevis. Noting that "stress hormone" corticosterone/cortisol secretion is linked to physiological processes, such as ovulation, that are not necessarily harmful to the individual, we suggest that the benefits of a doubling in egg yield-per-cycle per animal without loss of egg quality or signs of acute or long-term harm may outweigh the relatively modest and transient corticosterone elevation we observed. The double ovulation protocol therefore represents a potential new standard practice for promoting the "3Rs" (animal use reduction, refinement and replacement) mission for Xenopus research.

Loss of bmp15 function in the seasonal spawner Atlantic salmon results in ovulatory failure.

Bone morphogenetic protein 15 (BMP15) is an oocyte-specific growth factor important for successful female reproduction in mammals. While mutations in BMP15/Bmp15 cause ovulatory deficiency and/or infertility in certain mammalian species, loss of bmp15 in zebrafish, a continuous spawner and the only bmp15 knockout model in fish to date, results in complete arrest of follicle development and later female-to-male sex reversal, preventing to examine effects on ovulation/fertilization. Here, we used Atlantic salmon, a seasonal spawner, and generated bmp15 mutants to investigate ovarian development and fertility. Histological and morphometric analyses revealed that in biallelic frameshift (bmp15 fs/fs) mutant ovaries, folliculogenesis started earlier, resulting in an advanced development compared to wild-type (WT) controls, accompanied by a weaker expression of the (early) oocyte-specific factor figla. This precocious ovarian development was followed in bmp15 fs/fs females by enhanced follicle atresia during vitellogenic stages. Although genes involved in steroid synthesis and signaling (star, cyp11b, cyp17a1 and esr1) were dramatically higher in late vitellogenic bmp15 fs/fs mutant ovaries, estradiol-17ß plasma levels were lower than in WT counterparts, potentially reflecting compensatory changes at the level of ovarian gene expression. At spawning, bmp15 fs/fs females displayed lower gonado-somatic index values and reduced oocyte diameter, and the majority (71.4%), showed mature non-ovulating ovaries with a high degree of atresia. The remaining (28.6%) females spawned eggs but they either could not be fertilized or, upon fertilization, showed severe malformations and embryonic mortality. Our results show that Bmp15 is required for proper follicle recruitment and growth and later ovulatory success in Atlantic salmon, providing an alternative candidate target to induce sterility in farmed salmon. Moreover, since loss of bmp15 in salmon, in contrast to zebrafish, does not result in female-to-male sex change, this is the first mutant model in fish allowing further investigations on Bmp15-mediated functions in the ovulatory period.

Association of genomic prediction for twin pregnancies with the incidence of double ovulation in primiparous dairy cows.

Twin pregnancies compromise the health and well-being of dairy cattle. A recent genomic prediction model for twin pregnancies has been developed based on twin calving or abortion. However, the incidence of double ovulation is significantly higher than that of twin births. This study aimed to evaluate whether genomic prediction values for twin pregnancies are associated with the incidence of double ovulation in primiparous dairy cows. Factors influencing the double ovulation rate were analysed using binary logistic regression on 676 cows: 475 (70.3%) inseminated at spontaneous estrus and 201 following one of two different estrus synchronization protocols for fixed-time artificial insemination (FTAI). The odds ratio for double ovulations was 0.92 (p = .002) per unit increase in prediction value and 2 (p = .01) for cows subjected to an FTAI protocol. Our findings suggest that genomic prediction values for twin pregnancies can effectively identify the risk of double ovulation at the herd level.

Unmet needs in abnormal uterine bleeding due to ovulatory dysfunction.

Ovulatory disorders are a common cause of abnormal uterine bleeding in women of reproductive age. The International Federation of Gynecology and Obstetrics currently offers a causal classification system for ovulatory disorders but does not provide clear management recommendations. There remains regional disparity in treatment practices, often influenced by institutional and insurance regulations as well as cultural and religious practices. A panel of experts evaluated current gaps in ovulatory disorder management guidelines and discussed potential strategies for addressing these unmet needs. Key gaps included a lack in consensus about the effectiveness of combined estrogen and progestogen versus progestogen alone, a paucity of evidence regarding the relative effectiveness of distinct hormonal molecules, a lack of data regarding optimal treatment duration, and limited guidance on optimal sequencing of treatment. Recommendations included development of a sequential treatment-line approach and development of a clinical guide addressing treatment scenarios common to all countries, which can then be adapted to local practices. It was also agreed that current guidelines do not address the unique clinical challenges of certain patient groups. The panel discussed how the complexity and variety of patient groups made the development of one single disease management algorithm unlikely; however, a simplified, decision-point hierarchy could potentially help direct therapeutic choices. Overall, the panel highlighted that greater advocacy for a tailored approach to the treatment of ovulatory disorders, including wider consideration of non-estrogen therapies, could help to improve care for people living with abnormal uterine bleeding due to ovarian dysfunction.

History of the Development of Knowledge about the Neuroendocrine Control of Ovulation-Recent Knowledge on the Molecular Background.

The physiology of reproduction has been of interest to researchers for centuries. The purpose of this work is to review the development of our knowledge on the neuroendocrine background of the regulation of ovulation. We first describe the development of the pituitary gland, the structure of the median eminence (ME), the connection between the hypothalamus and the pituitary gland, the ovarian and pituitary hormones involved in ovulation, and the pituitary cell composition. We recall the pioneer physiological and morphological investigations that drove development forward. The description of the supraoptic-paraventricular magnocellular and tuberoinfundibular parvocellular systems and recognizing the role of the hypophysiotropic area were major milestones in understanding the anatomical and physiological basis of reproduction. The discovery of releasing and inhibiting hormones, the significance of pulse and surge generators, the pulsatile secretion of the gonadotropin-releasing hormone (GnRH), and the subsequent pulsatility of luteinizing (LH) and follicle-stimulating hormones (FSH) in the human reproductive physiology were truly transformative. The roles of three critical neuropeptides, kisspeptin (KP), neurokinin B (NKB), and dynorphin (Dy), were also identified. This review also touches on the endocrine background of human infertility and assisted fertilization.

A randomized single-blind non-inferiority trial of delayed start with drospirenone-only and ethinyl estradiol-gestodene pills for ovulation inhibition.

We compared the efficacy of 4 mg drospirenone (DRSP) progestin-only pills (POPs) versus combined oral contraceptive pills (COCs) containing 0.02 mg of ethinyl estradiol (EE) and 0.075 mg of gestodene (GS) in ovulation inhibition and inducing unfavorable cervical mucus changes using a delayed-starting approach. This randomized controlled trial involved 36 participants aged 18-45 years. The major outcomes included ovulation inhibition assessed using the Hoogland and Skouby score, and cervical mucus permeability, assessed using the modified World Health Organization score. The results demonstrated ovulation inhibition rates of 77.8% for the EE/GS group and 88.9% for the DRSP group. The risk ratio and absolute risk reduction were 0.50 (95% confidence interval [CI]: 0.10, 2.40) and - 0.11 (95% CI: - 0.35, 0.13), respectively, satisfying the 20% non-inferiority margin threshold. The median time to achieve unfavorable cervical mucus changes was comparable between the DRSP (3 days, interquartile range [IQR]: 6 days) and EE/GS (3.5 days, IQR: 4 days) groups. However, the DRSP group had a higher incidence of unscheduled vaginal bleeding (55.56% vs. 11.11%; p = 0.005). DRSP-only pills, initiated on days 7-9 of the menstrual cycle, were non-inferior to EE/GS pills in ovulation inhibition. However, they exhibited delayed unfavorable cervical mucus changes compared to the standard two-day backup recommendation.Clinical trial registration: Thai Clinical Trials Registry (TCTR20220819001) https://www.thaiclinicaltrials.org/show/TCTR20220819001 .

Novel Plasma Membrane Androgen Receptor SLC39A9 Mediates Ovulatory Changes in Cells of the Monkey Ovarian Follicle.

Follicular androgens are important for successful ovulation and fertilization. The classical nuclear androgen receptor (AR) is a transcription factor expressed in the cells of the ovarian follicle. Androgen actions can also occur via membrane androgen receptor SLC39A9. Studies in fish ovary demonstrated that androgens bind to SLC39A9 and increase intracellular zinc to regulate ovarian cell function. To determine if SLC39A9 is expressed and functional in the key cell types of the mammalian ovulatory follicle, adult female cynomolgus macaques underwent ovarian stimulation. Ovaries or ovarian follicular aspirates were harvested at 0, 12, 24, and 36 hours after human chorionic gonadotropin (hCG). SLC39A9 and AR mRNA and protein were present in granulosa, theca, and vascular endothelial cells across the entire 40-hour ovulatory window. Testosterone, bovine serum albumin-conjugated testosterone (BSA-T), and androstenedione stimulated zinc influx in granulosa, theca, and vascular endothelial cells. The SLC39A9-selective agonist (-)-epicatechin also stimulated zinc influx in vascular endothelial cells. Taken together, these data support the conclusion that SLC39A9 activation via androgen induces zinc influx in key ovarian cells. Testosterone, BSA-T, and androstenedione each increased proliferation in vascular endothelial cells, indicating the potential involvement of SLC39A9 in ovulatory angiogenesis. Vascular endothelial cell migration also increased after treatment with testosterone, but not after treatment with BSA-T or androstenedione, suggesting that androgens stimulate vascular endothelial cell migration through nuclear AR but not SLC39A9. The presence of SLC39A9 receptors and SLC39A9 activation by follicular androstenedione concentrations suggests that androgen activation of ovarian SLC39A9 may regulate ovulatory changes in the mammalian follicle.

Letrozole ovulation regimen for frozen-thawed embryo transfer in women with polycystic ovary syndrome: study protocol for a randomized controlled trial.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are usually selected to undergo an ovulation induction regimen or a programmed regimen for endometrial preparation in the frozen-thawed embryo transfer (FET) during their IVF/ICSI treatment. The programmed regimen permits flexible scheduling of embryo transfer but requires long-term usage of exogenous estrogen and higher dosages of luteal support while the letrozole ovulation regimen needs lower dosages of luteal support only. Recently, multiple studies have shown that the letrozole ovulation regimen can improve pregnancy outcomes of FET in women with PCOS compared with the programmed regimen. However, most of these studies are retrospective, and prospective studies are urgently needed the evidence from the perspective study is insufficient. METHODS/DESIGN: We are undertaking a multicentre, randomized, controlled clinical trial of an endometrial preparation regimen for FET in women with PCOS. The eligible women are randomly assigned to either the letrozole ovulation regimen or the programmed regimen for endometrial preparation. The primary outcome is the clinical pregnancy rate. DISCUSSION: The results of this study will provide evidence for whether the letrozole ovulation regimen for endometrial preparation could improve pregnancy outcomes in PCOS women undergoing FET. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200062244. Registered on 31 July 2022.

Identification of the FSH-RH as the other gonadotropin-releasing hormone.

In vertebrates, folliculogenesis and ovulation are regulated by two distinct pituitary gonadotropins: follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Currently, there is an intriguing consensus that a single hypothalamic neurohormone, gonadotropin-releasing hormone (GnRH), regulates the secretion of both FSH and LH, although the required timing and functions of FSH and LH are different. However, recent studies in many non-mammalian vertebrates indicated that GnRH is dispensable for FSH function. Here, by using medaka as a model teleost, we successfully identify cholecystokinin as the other gonadotropin regulator, FSH-releasing hormone (FSH-RH). Our histological and in vitro analyses demonstrate that hypothalamic cholecystokinin-expressing neurons directly affect FSH cells through the cholecystokinin receptor, Cck2rb, thereby increasing the expression and release of FSH. Remarkably, the knockout of this pathway minimizes FSH expression and results in a failure of folliculogenesis. Here, we propose the existence of the "dual GnRH model" in vertebrates that utilize both FSH-RH and LH-RH.

Livebirth rate after one frozen embryo transfer in ovulatory women starting with natural, modified natural, or artificial endometrial preparation in Viet Nam: an open-label randomised controlled trial.

BACKGROUND: Use of frozen embryo transfer (FET) in in-vitro fertilisation (IVF) has increased. However, the best endometrial preparation protocol for FET cycles is unclear. We compared natural and modified natural cycle strategies with an artificial cycle strategy for endometrial preparation before FET. METHODS: In this randomised, open-label study, we recruited ovulatory women aged 18-45 years at a hospital in Ho Chi Minh City, Viet Nam, who were randomly allocated (1:1:1) to natural, modified natural, or artificial cycle endometrial preparation using a computer-generated random list and block randomisation. The trial was not masked due to the nature of the study interventions. In natural cycles, no oestrogen, progesterone, or human chorionic gonadotropin (hCG) was used. In modified natural cycles, hCG was used to trigger ovulation. In artificial cycles, oral oestradiol valerate (8 mg/day from day 2-4 of menstruation) and vaginal progesterone (800 mg/day starting when endometrial thickness was ≥7 mm) were used. Embryos were vitrified, and then one or two day-3 embryos or one day-5 embryo were warmed and transferred under ultrasound guidance. If the first FET cycle was cancelled, subsequent cycles were performed with artificial endometrial preparation. The primary endpoint was livebirth after one FET. This trial is registered at ClinicalTrials.gov, NCT04804020. FINDINGS: Between March 22, 2021, and March 14, 2023, 4779 women were screened and 1428 were randomly assigned (476 to each group). 99 first FET cycles were cancelled in each of the natural and modified cycle groups, versus none in the artificial cycle group. The livebirth rate after one FET was 174 (37%) of 476 in the natural cycle strategy group, 159 (33%) of 476 in the modified natural cycle strategy group, and 162 (34%) of 476 in the artificial cycle strategy group (relative risk 1·07 [95% CI 0·87-1·33] for natural vs artificial cycle strategy, and 0·98 [0·79-1·22] for modified natural vs artificial cycle strategy). Maternal and neonatal outcomes did not differ significantly between groups, as the power to detect small differences was low. INTERPRETATION: Although the livebirth rate was similar after natural, modified natural, and artificial cycle endometrial preparation strategies in ovulatory women undergoing FET IVF, no definitive conclusions can be made regarding the comparative safety of the three approaches. FUNDING: None.

Equine chorionic gonadotropin (eCG) treatment in heifers: Double ovulation, twinning rate, and pregnancy losses in twin pregnancies.

This study aimed to evaluate the effects of different doses of equine chorionic gonadotropin (eCG; 200 and 300 IU) administered at the end of a fixed-time artificial insemination (FTAI) treatment protocol on ovulation, pregnancy, and twin rates in Bos taurus beef heifers. In addition, pregnancy losses in heifers with singleton and twin pregnancies were determined. A total of 2382 Angus heifers treated with a 6-day estradiol/progesterone-based protocol for FTAI (J-Synch protocol) were randomly allocated to two experimental groups to receive 200 or 300 IU of eCG administered intramuscularly at the time of intravaginal progesterone device removal; FTAI was performed from 60 to 72 h after device removal. The pregnancy rate did not differ (P = 0.89) between the 200 and 300 IU eCG groups. The number of corpus luteum induced by both eCG doses was determined by ultrasonographic examination 14 days after insemination and those treated with 300 IU of eCG had a greater double ovulation rate (P < 0.05). In addition, 300 IU eCG treated heifers had a higher twinning rate on day 30 of gestation (P < 0.05) and parturition (P < 0.05). Pregnancy losses from 30 days of gestation to calving did not differ between heifers treated with 200 and 300 IU of eCG (P = 0.70). However, regardless of the experimental group, heifers bearing twins had greater pregnancy losses than heifers with singletons (P < 0.05). In conclusion, reducing the dose of eCG from 300 to 200 IU under FTAI treatment protocol decreases double ovulation and twinning rates, maintaining a similar pregnancy rate in heifers. Nulliparous cows carrying two fetuses suffer greater pregnancy losses than cows with singletons.

Vitamin D binding protein correlate with estrogen increase after administration of human chorionic gonadotropin but do not affect ovulation, embryo, or pregnancy outcomes.

Background: Vitamin D binding protein (DBP) might increase substantially after ovarian stimulation and hence could be associated with IVF/ICSI outcomes because it determines the fraction of free bioavailable 25(OH) vitamin D. In this study, we aim to determine whether DBP is associated with E2 level after ovarian stimulation and IVF/ICSI outcomes. Design: Post-hoc analysis of a prospective observational cohort. Setting: Single-center study. Participants: 2569 women receiving embryo transfer. Intervention: None. Main outcome measures: The main outcomes were oocyte and embryo quality as well as pregnancy outcomes. Results: DBP concentration correlates with E2 on hCG day (=day of inducing ovulation with hCG; correlation coefficient r = 0.118, P<0.001) and E2 x-fold change to baseline level (r = 0.108, P<0.001). DBP is also positively correlated with total 25(OH)D (r = 0.689, R2 = 0.475, P<0.001) and inversely with free 25(OH)D (r=-0.424, R2=0.179, P<0.001), meaning that E2-stimulated DBP synthesis results in a decrease of free 25(OH)D during ovarian stimulation. However, such alteration does not affect IVF/ICSI outcomes when considering confounding factors, such as the number and quality of oocytes nor embryo quality as well as pregnancy outcomes. Conclusion: DBP concentration correlates with the degree of E2 increase after ovarian stimulation. DBP is also positively correlated with total 25(OH)D and inversely with free 25(OH)D, suggesting that the proportion of free 25(OH)D decreases during ovarian stimulation caused by E2-stimulated DBP synthesis. However, such alteration does not affect clinical IVF/ICSI outcomes.

Normal Ovarian Function in Subfertile Mouse with Amhr2-Cre-Driven Ablation of Insr and Igf1r.

Insulin receptor signaling promotes cell differentiation, proliferation, and growth which are essential for oocyte maturation, embryo implantation, endometrial decidualization, and placentation. The dysregulation of insulin signaling in women with metabolic syndromes including diabetes exhibits poor pregnancy outcomes that are poorly understood. We utilized the Cre/LoxP system to target the tissue-specific conditional ablation of insulin receptor (Insr) and insulin-like growth factor-1 receptor (Igf1r) using an anti-Mullerian hormone receptor 2 (Amhr2) Cre-driver which is active in ovarian granulosa and uterine stromal cells. Our long-term goal is to examine insulin-dependent molecular mechanisms that underlie diabetic pregnancy complications, and our conditional knockout models allow for such investigation without confounding effects of ligand identity, source and cross-reactivity, or global metabolic status within dams. Puberty occurred with normal timing in all conditional knockout models. Estrous cycles progressed normally in Insrd/d females but were briefly stalled in diestrus in Igf1rd/d and double receptor (DKO) mice. The expression of vital ovulatory genes (Lhcgr, Pgr, Ptgs2) was not significantly different in 12 h post-hCG superovulated ovaries in knockout mice. Antral follicles exhibited an elevated apoptosis of granulosa cells in Igf1rd/d and DKO mice. However, the distribution of ovarian follicle subtypes and subsequent ovulations was normal in all insulin receptor mutants compared to littermate controls. While ovulation was normal, all knockout lines were subfertile suggesting that the loss of insulin receptor signaling in the uterine stroma elicits implantation and decidualization defects responsible for subfertility in Amhr2-Cre-derived insulin receptor mutants.

The effects of green tea tablets and metformin on ovulation and menstrual cycle regularity in women with polycystic ovary syndrome.

Polycystic ovary syndrome is the most common cause of oligo-ovulation and anovulation among women of reproductive age, contributing to infertility. This study aimed to compare the effects of green tea tablets and metformin on ovulation, menstrual cycle regularity, and antioxidant biomarkers in women with polycystic ovary syndrome (PCOS). In this clinical trial study, 94 women with PCOS were randomly assigned to three groups: green tea (n = 33), metformin (n = 29), and control (n = 32). Menstrual status and oxidative stress parameters, including total antioxidant capacity, thiol, and lipid peroxidation, were compared before and 3 months after the intervention among all three groups. Data analysis was conducted using SPSS software version 22 and employing the analysis of variance and paired t-tests. Following the intervention, the mean menstrual cycle duration in the green tea, metformin, and control groups was 32.22 ± 12.78, 48.72 ± 37.06, and 48.53 ± 31.04 days, respectively (P = 0.040). There was no statistically significant difference between the three groups in terms of biochemical, hormonal, and antioxidant indices before and after the intervention (P > 0.05). The intake of green tea tablets was associated with better outcomes in regulating the menstrual cycle in women with PCOS.

Hormonal and circuit mechanisms controlling female sexual behavior.

Sexual behavior is crucial for reproduction in many animals. In many vertebrates, females exhibit sexual behavior only during a brief period surrounding ovulation. Over the decades, studies have identified the roles of ovarian sex hormones, which peak in levels around the time of ovulation, and the critical brain regions involved in the regulation of female sexual behavior. Modern technical innovations have enabled a deeper understanding of the neural circuit mechanisms controlling this behavior. In this review, I summarize our current knowledge and discuss the neural circuit mechanisms by which female sexual behavior occurs in association with the ovulatory phase of their cycle.

Surfeit locus protein 4 modulates endoplasmic reticulum function and maintains oocyte quality.

Surfeit locus protein 4 is a cargo receptor mediating cargo transport from the endoplasmic reticulum lumen to the Golgi apparatus. Loss of Surf4 gene led to embryonic lethality in mice. However, the role of Surf4 during oocyte development remains unknown. In this study, we generated the mouse model with oocyte-specific knockout of Surf4 gene. We found that adult mice with deletion of Surf4 showed normal folliculogenesis, ovulation and fertility. However, loss of Surf4 slightly impaired oocyte quality, thus led to partial oocyte meiotic arrest and reduced ratio of blastocyst formation. Consistent with this, the distribution of endoplasmic reticulum was disturbed in Surf4-deficient oocytes in mice. These results demonstrated that although Surf4 is dispensable for female mouse fertility, Surf4 modulates endoplasmic reticulum arrangement and participates in regulation of developmental competence of oocytes.