Reproduction & Fertility最新文献

Polycystic ovary syndrome (PCOS) is an endocrine metabolic disorder that appears to have a genetic predisposition and a fetal origin. The fetal ovary has two major somatic cell types shown previously to be of different cellular origins, different morphologies and to differentially express 15 genes. We isolated the somatic gonadal ridge epithelial-like (GREL) cells (n = 7) and ovarian fetal fibroblasts (n = 6) by clonal expansion. Using qRT-PCR, we compared the gene expression levels of PCOS candidate genes with previous data on the expression levels in whole fetal ovaries across gestation. We also compared these levels with those in bovine adult ovarian cells including fibroblasts (n = 4), granulosa cells (n = 5) and surface epithelial cells (n = 5). Adult cell types exhibited clear differences in the expression of most genes. In fetal ovarian cells, DENND1A and ERBB3 had significantly higher expression in GREL cells. HMGA2 and TGFB1I1 tended to have higher expression in fetal fibroblasts than GREL cells. Another 19 genes did not exhibit differences between GREL cells and fetal fibroblasts and FBN3, FSHB, LHCGR, FSHR and ZBTB16 were very lowly expressed in GREL cells and fibroblasts. The culture of fetal fibroblasts in EGF-containing medium resulted in lower expression of NEIL2, but higher expression of MAPRE1 compared to culture in the absence of EGF. Thus, the two fetal ovarian somatic cell types mostly lacked differential expression of PCOS candidate genes.

Risk factors associated with equine reproductive efficiency have been identified along with those associated specifically with early pregnancy loss (EPL). In contrast, no studies have reported risk factors associated with abortion (loss between day 70 and 300 post-cover). Given the causes of abortion differ to those of EPL, likely too will the risk factors. A retrospective cohort study was carried out to identify risk factors associated with abortion in UK and Irish based Thoroughbreds, collecting data on 20 exposure variables over a five-year period. A generalized linear mixed model was utilized to evaluate the associations between exposure variables and abortion, with clustering of observations accounted for at the mare and farm level. Variables with a likelihood ratio test (LRT) p value <0.2 were entered into the model in a forward stepwise approach. Pregnancy outcome was available on 4,439 pregnancies from 2,510 mares. Having had two or more prior abortions (odds ratio (OR) 7.91, 95% confidence interval (CI) 2.86, 21.88), conceiving on the second or subsequent covered estrous cycle (OR 1.84, 95% CI 1.22, 2.78) and conceiving multiple conceptuses (OR 1.68, 95% CI 1.02, 2.76) were associated with an increased risk of abortion compared to null parous, first estrous cycle covers and singleton conceptions respectively. Increasing paternal age (OR 0.95, 95% CI 0.90, 0.99) was associated with a decreasing risk of abortion. Mare and farm variance were not significant in the final model, LRT p=0.43. These findings provide evidence-based data to inform Thoroughbred breeding management practices to help mitigate abortion risk.

Ovarian platelet-rich plasma (PRP) is claimed to restore the fertility potential by improving reserve, an effect perhaps mediated epigenetically by platelet-discharged regulatory elements rather than gonadotropin-activated G-protein coupled receptors, as with stimulated in vitro fertilization (IVF). The finding that fresh activated platelet releasate includes factors able to promote developmental signaling networks necessary to enable cell pluripotency tends to support this theory. The mechanistic uncertainty of intraovarian PRP notwithstanding, at least two other major challenges confront this controversial intervention. The first challenge is to clarify how perimenopausal ovarian function is reset to levels consistent with ovulation. Perhaps a less obvious secondary problem is to confine this renewal such that any induced recalibration of cellular plasticity is kept within acceptable physiologic bounds. Thus, any 'drive' to ovarian rejuvenation must incorporate both accelerator and brake. Ovarian aging may be best viewed as a safeguard against pathologic overgrowth, where senescence operates as an evolved tumor-suppression response. While most ovary cells reach the close of their metabolic life span with low risk for hypertrophy, enhanced lysosomal activity and the proinflammatory 'senescence-associated secretory phenotype' usually offsets this advantage over time. But is recovery of ovarian fitness possible, even if only briefly prior to IVF? Alterations in gap junctions, bio-conductive features, and modulation of gene regulatory networks after PRP use in other tissues are discussed here alongside early data reported from reproductive medicine.

Abstract: Di-2-ethylhexyl phthalate (DEHP) is an extensively used plasticizer which has raised some concerns about its safety on human health. This study aimed at evaluating the effects of vanillic acid (VA) and vitamin C (VC) supplementation on DEHP-induced testicular toxicity. Thirty-five adult male Wistar rats were randomly divided into 7 groups (A-G) (n = 5) receiving distilled water; 250 mg/kg bw of DEHP only; 30 mg/kg bw of VA and 250 mg/kg bw of DEHP; 30 mg/kg bw of VC and 250 mg/kg bw of DEHP; 30 mg/kg bw of DEHP plus 30 mg/kg bw of VA and 30 mg/kg bw of VC; 30 mg/kg bw of VA only; and 30 mg/kg bw of VC only, respectively. At the end of the experiment, blood was taken from the heart via cardiac puncture and stored, semen was collected from the caudal epididymis for immediate sperm analysis, while the testes were excised and preserved for histological examination and biochemical analysis. The results showed a significant decrease (P < 0.05) in body weights, sperm motility, sperm volume, sperm viability and count, antioxidant levels, and reproductive hormonal levels, with a significant increase (P < 0.05) in sperm morphological defect and lipid peroxidation level in DEHP-only group compared with the control but was ameliorated after VA and VC administration compared to the DEHP-only treated animals. VA and VC supplementation attenuated the toxic effects of DEHP on the testicular functions, morphology, and semen characterization of the experimental adult male Wistar rats.

Lay summary: Male infertility is considered when identifiable female causes of infertility are excluded and semen quantity and quality fail to fulfil World Health Organization criteria. From conception through to adulthood, people are exposed to limitless environmental toxicants among which di-2-ethylhexyl phthalate (DEHP) commonly found in personal care products, cosmetics, and medical devices is prevalent. The present study elaborated on the importance of taking antioxidant-rich foods containing vitamin C and vanillic acid, such as those found in various fruits, olives, whole wheat, and cereal grains, in combating infertility caused by environmental toxicants. An experiment was carried out on rats to see the effect of vanillic acid and vitamin C supplementation on preventing DEHP-induced testicular toxicity. The testicles and semen were analyzed from five rats in each treated and control groups. The data led us to conclude that vanillic acid and vitamin C supplementation do have attenuating effects on DEHP-induced testicular toxicity, due to their high antioxidant and anti-inflammatory properties.

Abstract: Mitochondrial quality is implicated as a contributor to declining fertility with aging. We investigated mitochondrial transcripts in oocytes and their associated cumulus cells from mice of different ages using RNA-seq. Mice aged 3 weeks, 9 weeks, and 1 year were superovulated, and 48 h later, oocyte cumulus complexes were collected by follicle puncture. We did not detect any major differences that could be attributed to aging. However, mitochondrial RNA transcripts which deviated from the consensus sequence were found at a higher frequency in cumulus cells than in their corresponding oocyte. Previous investigations have shown that variation in the sequence of mtRNA transcripts is substantial, and at least some of this can be accounted for by post-transcriptional modifications which impact base calling during sequencing. Our data would be consistent with either less post-transcriptional modification in mitochondrial RNA from oocytes than cumulus cells or with lower mtDNA mutational load.

Lay summary: Women become less fertile as they age. Shortage of energy contributes to this, caused by a decline in the quality of mitochondria (the powerhouses of the cell) in the egg. Genes are the blueprint for the cell. They are made of DNA which is copied into an RNA message, or instructions, for making proteins. We counted differences in the RNA message of developing eggs and the cells that support them during development (cumulus cells). We compared the number of these differences in mice of different ages. These age groups represent mice had not reached puberty, those of prime reproductive age, and old mothers. We did not find any differences linked to the age of the mice. However, we did find differences between the egg and the cumulus cells. In most cases, there were lower levels of mutations in eggs than there were in cumulus cells.

Abstract: This study was carried out to investigate whether repeated controlled ovarian hyperstimulation (COH) affects ovarian reserve. For this reason, we aimed to show possible changes in the expression of PTEN and FOXO3, which are involved in preserving the over-reserve, after applying the COH protocol methods. For this purpose, 18 young Wistar albino female rats (8 weeks old) were randomly assigned as group 1 (control), group 2, and group 3 as 6 subjects in each group. Experimental groups were treated with 10 IU/0.1 mL pregnant mare's serum gonadotropin and a COH protocol consisting of 10 IU/0.1 mL human chorionic gonadotropin injection after 48 h. This procedure was applied three and five times to group 2 and group 3, respectively. For the control groups, the same procedures were performed with 0.1 mL of 0.9% sodium chloride solution. At the end of the experiment, the ovarium tissues were placed in a 10% neutral formaldehyde solution for light microscopic examinations. In histological sections stained with hematoxylin and eosin, the number of ovarian follicles was determined using the physical dissector method. However, the expression of PTEN, FOXO3, and LH-R molecules was evaluated by immunohistochemical methods. As a result of our study, it was concluded that COH administration reduces the expression levels of PTEN and FOXO3 proteins and LH-R, which are among the essential components of the PIK3 intracellular signaling pathway and also increased the levels of hormones such as follicle-stimulating hormone, estradiol, and luteinizing hormone, which are over-reserve markers, and causes adverse effects on the histological structure, oocyte morphology, and number of ovaries.

Lay summary: Today, approximately 10-15% of couples experience fertility problems. However, assisted reproductive techniques help people with fertility problems to get pregnant. The main purpose of these techniques is to put the sperm and egg together outside the woman's body where the eggs are fertilized and then to return the fertilized eggs (embryos) to the womb. During a woman's menstrual cycle, several hormones influence the growth of the eggs. This process can be mimicked by using various medications. Medication is given to increase the number of eggs that develop. However, this method is not the same as normal ovulation. Therefore, in our study, we wanted to examine the effect that developing multiple follicles has on the number and quality of eggs remaining for the future.

To gain more knowledge about the influence of hormone regulation on follicle development, ovarian ultrasounds were performed, and urinary hormone profiles were determined in ovulating and non-ovulating female bottlenose dolphins (n = 15) following estrus synchronization with altrenogest. Ovarian ultrasounds were conducted daily, post synchronization to describe follicular recruitment in relationship to the endocrine profile. Follicle sizes were grouped into very small (VSM), small (SM), medium (MD) and large (LG). In ovulating females, two follicular waves were identified, and follicular deviation towards establishing a dominant follicle only occurred during the second wave. For non-ovulating females, only the first wave was observed. For all urinary hormones, the non-ovulating group presented significantly lower concentrations of follicle stimulating hormone (uFSH), luteinizing hormone (uLH), estrone conjugates (uE1-C) and estriol (uE3) but similar progestagen and cortisol concentrations compared to the ovulating group. Concentrations of uE1-C and uE3 and numbers of MD and LG follicles significantly (P < 0.05) increased, while uFSH concentrations significantly (P < 0.05) decreased as ovulation approached. Urinary LH significantly increased concurrently with increasing numbers of LG follicles and decreasing numbers of SM follicles. The characterization of follicular development and its relationship with hormone assessments complements our understanding of follicular recruitment post-synchronization in bottlenose dolphins and provides new information concerning differences between ovulating and non-ovulating females in response to an estrous synchronization protocol.

Concern about fertility impairment after vaccination is one of the reasons for vaccine hesitancy in the population. This retrospective observational study aims to understand the impact of CovishieldTM (ChAdOx1 nCoV- 19 Corona Virus Vaccine, Recombinant) COVID-19 vaccination on ejaculate quality in fifty-three patients undergoing semen analysis between 2018 to 2021. A baseline semen profile was recorded from the subjects during their visit before the vaccination for fertility work-up. Follow-up ejaculates were provided approximately 82 (Q1:37, Q3:124) days after the second dose of vaccination. Semen characteristics such as volume, sperm concentration, sperm motility, and morphological abnormalities were recorded. Of the 53 subjects, 33 (62%) had semen characteristics above the WHO reference. In general, no significant variations in the semen parameters were observed except for a moderate decline in sperm morphology (p< 0.05). The baseline semen characteristics in 20 (38%) subjects were below the WHO reference range; however, no significant decline in the ejaculate quality was observed in their follow-up samples. Further, none of the ejaculates in both study groups were azoospermic during the follow-up evaluation. Our results affirm that CovishieldTM vaccine is not detrimental to male fertility.

Infertility is a time-consuming and exhaustive process, which disproportionally affects women. Although concerns have been raised about deficiencies in clinical evaluation of infertile men, there is currently little published data documenting this. A SurveyMonkey questionnaire was therefore created to capture current clinical practice of fertility specialists working in IVF clinics. Responses were collected May - July 2021. 112 clinicians completed the pilot survey with respondents from Europe (n=49; 43.8%), Africa (n=39, 34.8%), North America (n=6; 5.4%), Asia (n=16; 14.3%), South America (n=1; 0.9%) and Australasia (n=1;0.9%). 41% fertility specialists (45/110) reported taking only a brief medical history and 24% reported that they never routinely examined infertile male patients. 54% fertility specialists also reported issues getting men to undertake diagnostic semen analysis. Treatment for male infertility spanned Assisted Reproductive Technology (ART), with themes of individualised medicine influencing treatment recommendations. 48.2% clinicians reported using empirical medical therapy (EMT) for unexplained male infertility. Notably, 3.6% respondents recommended testosterone treatment, despite likely negative impact on spermatogenesis. However, high levels of opportunistic general health advice were reported, including discussion of life exposures thought to be important for male reproductive health. This study adds novel evidence and highlights current deficiencies in clinical practice relating to male infertility. Evaluation of the infertile male using simple medical tools (detailed history taking and clinical examination) has the potential to identify treatable or reversible conditions and should be an immediate focus for education and improvement in Reproductive Medicine. Investment in research and development is much needed in the field of andrology, to develop effective non-ART treatment options for male infertility.