https://www.fertstert.org/article/S0015-0282(14)02371-1/pdf

Oocyte environment: follicular fluid and cumulus cells are critical for oocyte health

Apoptosis causes elimination of more than 99% of germ cells from cohort of ovary through follicular atresia. Less than 1% of germ cells, which are culminated in oocytes further undergo apoptosis during last phases of oogenesis and depletes ovarian reserve in most of the mammalian species including human. There are several players that induce apoptosis directly or indirectly in oocytes at various stages of meiotic cell cycle. Premature removal of encircling granulosa cells from immature oocytes, reduced levels of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate, increased levels of calcium (Ca(2+)) and oxidants, sustained reduced level of maturation promoting factor, depletion of survival factors, nutrients and cell cycle proteins, reduced meiotic competency, increased levels of proapoptotic as well as apoptotic factors lead to oocyte apoptosis. The BH3-only proteins also act as key regulators of apoptosis in oocyte within the ovary. Both intrinsic (mitochondria-mediated) as well as extrinsic (cell surface death receptor-mediated) pathways are involved in oocyte apoptosis. BID, a BH3-only protein act as a bridge between both apoptotic pathways and its cleavage activates cell death machinery of both the pathways inside the follicular microenvironment. Oocyte apoptosis leads to the depletion of ovarian reserve that directly affects reproductive outcome of various mammals including human. In this review article, we highlight some of the important players and describe the pathways involved during oocyte apoptosis in mammals.

Apoptosis in mammalian oocytes: a review.

STUDY QUESTION: Does the prewash total motile sperm count (TMSC) have a better predictive value for spontaneous ongoing pregnancy (SOP) than the World Health Organization (WHO) classification system? SUMMARY ANSWER: The prewash TMSC shows a better correlation with the spontaneous ongoing pregnancy rate (SOPR) than the WHO 2010 classification system. WHAT IS KNOWN ALREADY: According to the WHO classification system, an abnormal semen analysis can be diagnosed as oligozoospermia, astenozoospermia, teratozoospermia or combinations of these and azoospermia. This classification is based on the fifth percentile cut-off values of a cohort of 1953 men with proven fertility. Although this classification suggests accuracy, the relevance for the prognosis of an infertile couple and the choice of treatment is questionable. The TMSC is obtained by multiplying the sample volume by the density and the percentage of A and B motility spermatozoa. STUDY DESIGN, SIZE, DURATION: We analyzed data from a longitudinal cohort study among unselected infertile couples who were referred to three Dutch hospitals between January 2002 and December 2006. Of the total cohort of 2476 infertile couples, only the couples with either male infertility as a single diagnosis or unexplained infertility were included (n = 1177) with a follow-up period of 3 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: In all couples a semen analysis was performed. Based on the best semen analysis if more tests were performed, couples were grouped according to the WHO classification system and the TMSC range, as described in the Dutch national guidelines for male infertility. The primary outcome measure was the SOPR, which occurred before, during or after treatments, including expectant management, intrauterine insemination, in vitro fertilization or intracytoplasmic sperm injection. After adjustment for the confounding factors (female and male age, duration and type of infertility and result of the postcoital test) the odd ratios (ORs) for risk of SOP for each WHO and TMSC group were calculated. The couples with unexplained infertility were used as reference. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 514 couples did and 663 couples did not achieve a SOP. All WHO groups have a lower SOPR compared with the unexplained group (ORs varying from 0.136 to 0.397). Comparing the couples within the abnormal WHO groups, there are no significant differences in SOPR, except when oligoasthenoteratozoospermia is compared with asthenozoospermia [OR 0.501 (95% CI 0.311-0.809)] and teratozoospermia [OR 0.499 (95% CI: 0.252-0.988)], and oligoasthenozoospermia is compared with asthenozoospermia [OR 0.572 (95% CI: 0.373-0.877)]. All TMSC groups have a significantly lower SOPR compared with the unexplained group (ORs varying from 0.171 to 0.461). Couples with a TMSC of <1 x 10(6) and 1-5 x 10(6) have significantly lower SOPR compared with couples with a TMSC of 5-10 x 10(6) [respectively, OR 0.371 (95% CI: 0.215-0.64) and OR 0.505 (95% CI: 0.307-0.832)]. LIMITATIONS, REASON FOR CAUTION: To include all SOPs during the follow-up period of 3 years, couples were not censured at the start of treatment. WIDER IMPLICATIONS OF THE FINDINGS: Roughly, three prognostic groups can be discerned: couples with a TMSC <5, couples with a TMSC between 5 and 20 and couples with a TMSC of more than 20 x 10(6) spermatozoa. We suggest using TMSC as the method of choice to express severity of male infertility. STUDY FUNDING/COMPETING INTERESTS: None.

Total motile sperm count: a better indicator for the severity of male factor infertility than the WHO sperm classification system

Context: Vitamin D deficiency is common among reproductive-aged women and has a role in female reproduction. Objective: This study evaluated the role of 1,25-dihydroxyvitamin D3 (vit D3) in ovarian follicular development and steroidogenesis by using a human granulosa cell (GC) model. Design, Setting, and Participants: Fifty-four women who underwent in vitro fertilization were enrolled. Intervention: Follicular fluid (FF) and mural and cumulus GCs were collected from small and large follicles. In separate experiments, primary cumulus GCs were cultured with or without vit D3 followed by RT-PCR for mRNA expression levels. The effect of recombinant anti-Mullerian hormone (AMH) on nuclear localization of phospho-Smad 1/5/8 was evaluated in the presence or absence of vit D3 by using immunofluorescence. 25-Hydroxyvitamin D levels in FF as well as cell culture media AMH, progesterone, and estradiol (E2) concentrations were determined by ELISA and RIA. Main Outcome Measures: The following were measured: 1) mRNA ex...

/pdf/vitamin-d-alters-genes-involved-in-follicular-development-2w5ipenub8.pdf

Vitamin D alters genes involved in follicular development and steroidogenesis in human cumulus granulosa cells.

Identification of Maturation-Specific Proteins by Single-Cell Proteomics of Human Oocytes

Cumulus and granulosa cell markers of oocyte and embryo quality

The steroid hormone vitamin D is historically recognized for its relevance to bone health and calcium homeostasis. Recent years have witnessed a shift in focus to non-skeletal benefits of vitamin D; in this latter context, an accruing body of literature attests to a relevance of vitamin D to reproductive physiology. This article reviews the existing data about the diverse and previously underappreciated roles for vitamin D in reproductive health. A large body of available literature suggests that vitamin D deficiency may be detrimental to reproductive biology. However, given that our appreciation of vitamin D's role in reproductive physiology is almost entirely shaped by 'associative' studies and that data based on prospective interventional trials are limited, these concepts remain predominantly conjectural. Exact mechanisms whereby vitamin D may participate in the regulation of reproductive physiology remain far from clear. This review underscores a need for appropriately designed intervention trials to address the existing knowledge gaps and to delineate the specific roles of vitamin D signaling in reproductive biology.

Relevance of vitamin D in reproduction

Premature ovarian insufficiency is a complex and relatively poorly understood entity with a myriad of etiologies and multisystem sequelae that stem from premature deprivation of ovarian sex hormones. Timely diagnosis with a clear understanding of the various comorbidities that can arise from estrogen deficiency is vital to appropriately counsel and treat these patients. Prompt initiation of hormone therapy is critical to control the unsolicited menopausal symptoms that many women experience and to prevent long-term health complications. Despite ongoing efforts at improving our understanding of the mechanisms involved, any advancement in the field in recent decades has been modest at best and researchers remain thwarted by the complexity and heterogeneity of the underpinnings of this entity. In contrast, the practice of clinical medicine has made meaningful strides in providing assurance to the women with premature ovarian insufficiency that their quality of life as well as long-term health can be optimized through timely intervention. Ongoing research is clearly needed to allow pre-emptive identification of the at-risk population and to identify mechanisms that if addressed in a timely manner, can prolong ovarian function and physiology.

/pdf/premature-ovarian-insufficiency-an-update-on-recent-advances-2z6j6fjyxe.pdf

Premature Ovarian Insufficiency - an update on recent advances in understanding and management

GnRH agonists (GnRHa) are increasingly used for fertility preservation in women undergoing gonadotoxic chemotherapy. However, the protective mechanisms of action for these compounds have not yet been elucidated. In this study, we aimed to determine whether GnRHa have a direct effect on ovarian granulosa cells. GnRH receptor (GnRHR) expression was determined in mouse somatic and gonadal tissues including granulosa/cumulus cells and oocytes using quantitative RT-PCR and immunohistochemistry. Granulosa cells were isolated from mouse ovaries primed with pregnant mare serum gonadotropin. Response to GnRHa in cultured granulosa cells was assessed by determining the increase of intracellular cAMP and by assessing phosphorylation of downstream mediators of GnRH signaling: ERK and p38. To measure intracellular cAMP in our system, the cells were transfected with a cAMP-responsive luciferase reporter plasmid and stimulated with GnRHa. For all experiments, pituitary tissue and/or the αT3–1 mouse pituitary cell line were used as controls. GnRHR mRNA and protein were detected in mouse ovaries, granulosa/cumulus cells, and oocytes. After GnRHa stimulation at various time intervals, we were unable to detect a cAMP increase or activation of the ERK or p38 signaling pathway in cultured primary mouse granulosa cells, whereas activation was detected in the control αT3–1 mouse pituitary cells. In this study, we have not detected activation of the canonical GnRH signaling pathways in mouse ovarian somatic cells. Our findings suggest that the mechanism of action of GnRHa in the ovary is either below the detection level of our experimental design or is different from that in the pituitary.

Characterization of the gonadotropin releasing hormone receptor (GnRHR) expression and activity in the female mouse ovary.

PURPOSE OF REVIEW With the recent advancements in reproductive medicine, many infertile couples now have the opportunity to conceive their own biological children. Although some medication protocols, such as clomiphene citrate, have been utilized for decades, other treatment modalities have evolved over the recent years. It therefore becomes imperative to assess the outcomes of these modalities and be critical regarding their safety. Pregnancy loss is one outcome that can affect many couples who conceive both spontaneously and with assistance via fertility treatment. In this review, several of the most commonly used fertility treatments will be discussed and the impact, if any, they may have in early pregnancy loss will be addressed. RECENT FINDINGS Current data do not support that notion that infertility treatments or assisted reproductive techniques contribute to early pregnancy loss. However, more studies are needed to eliminate the confounding variables that make data interpretation difficult to generalize to the infertile population. SUMMARY An early pregnancy loss can cause emotional distress and grief, particularly for couples already dealing with an infertility diagnosis. Therefore, knowledge regarding the relationship between infertility and early pregnancy loss is vital in order to properly counsel the couple prior to starting treatment.

Saioa Torrealday

Papers

Cumulus and granulosa cell markers of oocyte and embryo quality

Relevance of vitamin D in reproduction

Premature Ovarian Insufficiency - an update on recent advances in understanding and management

Characterization of the gonadotropin releasing hormone receptor (GnRHR) expression and activity in the female mouse ovary.

Is the fertility treatment itself a risk factor for early pregnancy loss