Reproductive aging is associated with altered gene expression in human luteinized granulosa cells.

Declining reproductive success with aging is attributable to qualitative and quantitative deterioration in oocytes, which are nurtured by granulosa cells (GCs). This prospective study assesses whether reproductive aging is accompanied by differential gene expression in luteinized GCs from in vitro fertilization (IVF) patients. Women with nonovarian infertility etiologies were categorized as younger (< or =30, n = 3) or older (> or =40, n = 3). During oocyte retrieval, mural GCs were isolated; messenger RNA (mRNA) was extracted and transcribed for complementary DNA (cDNA) microarray analysis. Differential gene expression was confirmed by real-time polymerase chain reaction (PCR). Analysis revealed 120 genes were differentially expressed. Three genes were upregulated and 117 were downregulated (including interleukin [IL]-1beta, IL-1R2, and IL-6R) in GCs of older versus younger patients. Our data provide evidence of downregulation in IL-1 and IL-6 gene families in luteinized GCs with advancing age. Given previously recognized roles for the IL gene family in folliculogenesis and ovulation, our findings may partly explain ovulatory and luteal dysfunctions associated with reproductive aging.

Inhibins, activins, and follistatin in the aging female and male.

Dimeric inhibins, activins, and follistatin (FS) were all initially characterized as reproductive endocrine hormones that regulate follicle-stimulating hormone (FSH) secretion. This model, however, has expanded under the weight of current medical evidence. Activin appears to play a central auto/paracrine role in reproductive and nonreproductive tissues. Inhibin and FS each have important counterregulatory functions in activin signaling. With reproductive aging, inhibin B declines along with the follicular pool and disturbs the dynamics of the normal menstrual cycle of midreproductive age. The loss of inhibin restraint of FSH secretion appears to be the initiating endocrine event that leads to menstrual cycle shortening and some of the hormonal unpredictability of the late reproductive years. It may also be related to the decline in fertility that occurs in reproductive aging. In men, inhibin B is an excellent marker for gonadal competence, and the decline of inhibin B with age reflects decreased gonadal reserve in both sexes. Circulating activin increases with aging, but its effect on reproduction in women and men is not clear. FS does not appear to change greatly with aging in men or women. The age-related fluctuations in this delicately balanced regulatory triad influence reproductive capacity and the sequelae of chronological aging. Elucidation of the molecular pathways responsible for the action of these hormones may allow closer integration with their current conceptual roles in aging.

Postmortem parenthood and the need for a protocol with posthumous sperm procurement.

OBJECTIVE: Posthumous sperm procurement involves harvesting gametes from a recently deceased man for cryopreservation and future use in ART. This paper discusses the practical and ethical role of posthumous sperm procurement in medical practice and society and submits possible solutions, including the establishment of formal policies and protocols. DESIGN: English-language literature review and bioethical discussion. RESULT(S): In the United States, an increase in requests and protocols has been documented. International requests and regulation are variable. CONCLUSION(S): Posthumous sperm procurement is fraught with ethical dilemmas, including informed consent, privacy, inheritance, and child welfare. To establish appropriate medical practice, it is important to consider all stakeholders in the decision-making process. We believe that an acceptable and ethical resolution can be obtained only through the collaborative input of all involved parties. We have looked to U.S. and international sources for guidance in current practice and to gain insight into the formulation of future policies.