The 5.8S pre‐rRNA maturation factor, M‐phase phosphoprotein 6, is a female fertility factor required for oocyte quality and meiosis

AbstractMany integral membrane proteins might act as indispensable coordinators in specific functional microdomains to maintain the normal operation of known receptors, such as Notch. Gm364 is a multi-pass transmembrane protein that has been screened as a potential female fertility factor. However, there have been no reports to date about its function in female fertility. Here, we found that global knockout of Gm364 decreased the numbers of primordial follicles and growing follicles, impaired oocyte quality as indicated by increased ROS and γ-H2AX, decreased mitochondrial membrane potential, decreased oocyte maturation, and increased aneuploidy. Mechanistically, Gm364 directly binds and anchors MIB2, a ubiquitin ligase, on the membrane. Subsequently, membrane MIB2 ubiquitinates and activates DLL3. Next, the activated DLL3 binds and activates Notch2, which is subsequently cleaved within the cytoplasm to produce NICD2, the intracellular active domain of Notch2. Finally, NICD2 can directly activate AKT within the cytoplasm to regulate oocyte meiosis and quality.

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Melatonin in male and female fertility

AL-Kindy College Medical Journal ◽

10.47723/kcmj.v17i3.398 ◽

2021 ◽

Vol 17 (3) ◽

pp. 145-151

Author(s):

Zainab M. Alawad ◽

Hanan L. Al-Omary

Keyword(s):

Positive Impact ◽

Sperm Quality ◽

Neurological Diseases ◽

Oocyte Quality ◽

The Body ◽

Female Fertility ◽

Male And Female ◽

Vitro Fertilization ◽

Cancer Agent

Melatonin, a hormone synthesized mainly by the pineal gland, has been found in extra-pineal organs as well. It’s known as an organizer of circadian rhythms and more recently as an anti-oxidant. In addition to its role in maintaining immunity, pathophysiology of cardiovascular and neurological diseases, and as an anti-cancer agent, evidence has demonstrated that melatonin exerts a positive impact on male and female fertility primarily through oxygen scavenging effects. In In Vitro Fertilization (IVF) programs, supplementation of melatonin may be associated with better outcomes in terms of sperm quality, oocyte quality, embryo quality and pregnancy rates. This review summarizes various actions of melatonin on the body focusing on male and female fecundity.

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The Impact of Preconceptional Multiple-Micronutrient Supplementation on Female Fertility

Clinical Medicine Insights Women s Health ◽

10.1177/1179562x19843868 ◽

2019 ◽

Vol 12 ◽

pp. 1179562X1984386 ◽

Cited By ~ 1

Author(s):

Ella Schaefer ◽

Deborah Nock

Keyword(s):

Oxidative Stress ◽

Oocyte Quality ◽

Female Fertility ◽

Micronutrient Supplementation ◽

Industrialized Countries ◽

Childbearing Age ◽

Micronutrient Status ◽

Modifiable Factors ◽

Multiple Micronutrient ◽

The Impact

In industrialized countries, fertility has declined in recent years to the lowest recorded levels. Identifying modifiable factors that influence human fertility, such as diet, is therefore of major clinical and public health relevance. Micronutrient status is a modifiable risk factor that may have an impact on female fertility, as essential vitamins and minerals have important roles in the physiological processes that are involved. Adequate levels are important for oocyte quality, maturation, fertilization, and implantation, whereas antioxidants are vital to reduce oxidative stress, a process known to impair fertility. In women who are diagnosed as infertile, lower than recommended levels of certain micronutrients have been reported. A similar scenario has been found in a proportion of women of childbearing age in general, some of whom may be struggling to conceive. Supplementation studies with multiple micronutrients are still scarce, but the literature suggests that supplementation before conception can help restore micronutrient status to recommended levels and reduce oxidative stress when antioxidants are included. Overall, supplementation has a small but beneficial effect on fertility in healthy and infertile women, including a shorter time to pregnancy and an increased chance of becoming pregnant. Nevertheless, many studies are small or observational, and adequately powered randomized controlled trials of supplementation with multiple micronutrients are necessary to confirm any definite effects on fertility. This review substantiates the potential benefits of micronutrient supplementation beyond the prevention of neural tube defects, the traditionally viewed value of prenatal vitamin use.

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Ovarian ageing and the impact on female fertility

F1000Research ◽

10.12688/f1000research.16509.1 ◽

2018 ◽

Vol 7 ◽

pp. 1835 ◽

Cited By ~ 8

Author(s):

Beverley Vollenhoven ◽

Sarah Hunt

Keyword(s):

Predictive Models ◽

Current Knowledge ◽

Threshold Level ◽

Oocyte Quality ◽

Female Fertility ◽

Menopausal Transition ◽

Oocyte Number ◽

Age Related ◽

The Impact

Female fertility decreases with increasing age, a reflection of declining oocyte quantity and quality. The menopausal transition occurs when the oocyte quantity falls below a threshold level. The pattern of follicular depletion as well as the factors, timing and mechanisms surrounding both declining oocyte number and oocyte quality remain incompletely understood. Further studies are needed to examine the factors involved and develop predictive models and biomarkers to assist in the management of age-related subfertility. This review summarises the current knowledge addressing the ageing ovary and its impact on fertility.

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Female fertility preservation: Impact of cancer on ovarian function and oocyte quality

International Journal of Gynecology & Obstetrics ◽

10.1002/ijgo.13702 ◽

2021 ◽

Author(s):

Cristina Fabiani ◽

Maria Giulia Ferrante ◽

Caterina Meneghini ◽

Emanuele Licata ◽

Gemma Paciotti ◽

...

Keyword(s):

Fertility Preservation ◽

Ovarian Function ◽

Oocyte Quality ◽

Female Fertility ◽

Female Fertility Preservation

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065. THE MAMMALIAN OOCYTE: FROM BENCH TO CLINIC

Reproduction Fertility and Development ◽

10.1071/srb09abs065 ◽

2009 ◽

Vol 21 (9) ◽

pp. 18

Author(s):

R. B. Gilchrist

Keyword(s):

Somatic Cells ◽

Cumulus Cells ◽

Reproductive Technologies ◽

Oocyte Quality ◽

Female Fertility ◽

Widespread Application ◽

Developmental Potential ◽

Mammalian Oocyte ◽

Wide Range

The mature mammalian oocyte is the central link between generations. It is not only responsible for the transfer of the female genome between generations, but also largely determines embryo and early fetal developmental potential. For any female, oocytes are in limited supply and are easily damaged, such that the availability of high quality or developmentally competent oocytes is a fundamental rate-limiting factor in female fertility. This is particularly relevant in Australian society today with the steadily rising age to first conception which adversely affects oocyte quality and female fertility. Yet despite years of research and clinical IVF we still have a poor understanding of the molecular and cellular processes that control oocyte quality. It is clear that oocytes acquire developmental competence in the ovarian follicle. The acquisition of competence necessitates communication between the oocyte and maternal systems, a process which endows developmental potential as the oocyte grows and matures inside the follicle. At the cellular level this is achieved by bi-directional communication between oocytes and their companion somatic cells [1]. Over the past 10 years my laboratory has focused heavily on the nature of these oocyte-somatic communication axes and their impact on oocyte quality. Over this period, our work and that of others has shaped a new paradigm in ovarian biology, which is that the oocyte is not passive in the follicle, but rather that it actively directs the differentiation of its neighbouring somatic cells into cumulus cells through the secretion of GDF9 and BMP15 growth factors [2]. In doing so, oocytes dictate the function of their neighboring cumulus cells, directing them to perform functions needed for the appropriate growth and development of the oocyte. For example, cumulus cells supply oocytes with an array of nutrients, substrates and regulatory molecules such as cAMP, many directly through gap-junctions. These communication axes establish and maintain an elaborate and intricate local oocyte-cumulus auto regulatory loop that is required to enable post-fertilisation development. A clear clinical application of this new knowledge is in Artificial Reproductive Technologies, in particular oocyte in vitro maturation (IVM) [3]. IVM biotechnologies have the capacity to capture the vast supply of oocytes in the mammalian ovary and generate mature oocytes in vitro. Generating offspring using IVM is already a clinically and commercially viable biotechnology in livestock breeding programs, particularly in cattle. IVM is a particularly attractive technology for the treatment of human infertility, as it removes the need for expensive and potentially harmful ovarian hyperstimulation protocols used in clinical IVF. However, widespread application of IVM in humans requires an increase in efficiency and further examination of safety of the technology. Recent work from my laboratory has increased IVM success rates in animals by using GDF9 and BMP15 in IVM [2, 3] and by developing a new system of “Induced-IVM” that more closely resembles the mechanisms of oocyte maturation in vivo. Most recently, the latter approach has led to substantial increases in embryo yield and pregnancy outcomes to levels equivalent to hormone-stimulated IVF [4]. The next challenge is to adapt these new approaches to clinical/field conditions to provide new opportunities for infertile women and for the development of a wide range of reproductive biotechnologies.

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126 Subcortical maternal complex (SCMC) expression during folliculogenesis is affected by oocyte donor age in sheep

Reproduction Fertility and Development ◽

10.1071/rdv32n2ab126 ◽

2020 ◽

Vol 32 (2) ◽

pp. 190

Author(s):

D. Bebbere ◽

A. Abazari-Kia ◽

F. Ariu ◽

L. Bogliolo ◽

S. Ledda

Keyword(s):

Molecular Mechanisms ◽

Oocyte Quality ◽

Arginine Deiminase ◽

Female Fertility ◽

Developmental Competence ◽

Donor Age ◽

Oocyte Growth ◽

Aberrant Expression ◽

Pyrin Domain ◽

Age Related

Age-associated decline in female fertility is largely attributable to decrease in oocyte quality. However, the molecular mechanisms that shape oocyte developmental competence, and that may be involved in reproductive aging, are yet to be elucidated. The subcortical maternal complex (SCMC) is a multiprotein complex located in the subcortex of oocytes that is essential for early embryogenesis and female fertility. It appears to be functionally conserved across mammals; aberrant expression of its members was observed in several animal models of differential competence, and mutations in human SCMC genes were associated with certain human reproductive disorders. At least seven proteins contribute to the complex: KH domain-containing 3 like (KHDC3/FILIA), NLR family pyrin domain-containing 2 (NLRP2), NLRP5 (MATER), oocyte expressed protein (OOEP), peptidyl arginine deiminase 6 (PADI6), transducin-like enhancer of split 6 (TLE6), and zinc finger BED-type-containing 3 (ZBED3), all encoded by maternal effect genes (MEGs). The aim of the present work was to evaluate expression dynamics of the SCMC components during folliculogenesis in relation to maternal age in sheep. Total RNA was isolated and reverse-transcribed from pools of denuded growing oocytes (GO) of different diameters (70-90μm (small, S), 90-110μm (medium, M), or 110-130μm (large, L)) derived from nonhormonally treated prepubertal (Pr, age 40 days), adult (Ad, age <4 years), or aged (Aged, age >6 years) animals (5 pools of 30 oocytes per experimental group). The SCMC expression was assessed by real-time PCR (PCR efficiency of 90-110% and correlation coefficient r2>0.99). Data were normalized against oocyte number and an exogenous spike-in mRNA, Luciferase, as reference gene. Expression dynamics were analyzed within each age group (general linear model ANOVA). Strikingly, patterns specifically associated with donor age were observed during folliculogenesis for six of the seven SCMC components. The Pr group showed active transcription of all mRNA, except ZBED3, during the entire window of oocyte growth (P<0.05). On the contrary, the similar abundance of NLRP2, NLRP5, PADI6, and ZBED3 in Ad S, M, and L GO suggests earlier storage during folliculogenesis; FILIA, OOEP, and TLE6 showed an increase between Ad S and M GO (P<0.05), indicating that the synthesis of these transcripts is complete at this stage (M GOs). Notably, oocytes derived from Aged donors showed a completely inverse expression pattern, with a decrease in abundance of NLRP2, TLE6, FILIA, and PADI6 mRNAs during the last stage of oocyte growth (L GO; P<0.05). Interestingly, MATER showed very high variability in expression (standard error (SE) ranging from 0.79 to 1.13 quantitation cycles (Cq)) in Aged GO, compared to Ad GO (SE 0.16-0.24 Cq) or Pr GO (SE 0.16-0.26 Cq), suggesting large inter-oocyte differences. In conclusion, age affects the storage of the MEGs encoding the SCMC during folliculogenesis. The observed depletion in SCMC transcripts in GO of aged donors is likely to be involved in the age-related decline in oocyte quality.

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