Inbreeding uncovers fundamental differences in the genetic load affecting male and female fertility in a butterfly

Inbreeding depression is most pronounced for traits closely associated with fitness. The traditional explanation is that natural selection eliminates deleterious mutations with additive or dominant effects more effectively than recessive mutations, leading to directional dominance for traits subject to strong directional selection. Here we report the unexpected finding that, in the butterfly Bicyclus anynana, male sterility contributes disproportionately to inbreeding depression for fitness (complete sterility in about half the sons from brother-sister matings), while female fertility is insensitive to inbreeding. The contrast between the sexes for functionally equivalent traits is inconsistent with standard selection arguments, and suggests that trait-specific developmental properties and cryptic selection play crucial roles in shaping genetic architecture. There is evidence that spermatogenesis is less developmentally stable than oogenesis, though the unusually high male fertility load in B. anynana additionally suggests the operation of complex selection maintaining male sterility recessives. Analysis of the precise causes of inbreeding depression will be needed to generate a model that reliably explains variation in directional dominance and reconciles the gap between observed and expected genetic loads carried by populations. This challenging evolutionary puzzle should stimulate work on the occurrence and causes of sex differences in fertility load.

Prokineticin ligands and receptors are expressed in the human fetal ovary and regulate germ cell expression of COX2

CONTEXT: Fetal ovarian development and primordial follicle formation underpin future female fertility. Prokineticin (PROK) ligands regulate cell survival, proliferation and angiogenesis in adult reproductive tissues including the ovary. However, their expression and function during fetal ovarian development remains unclear.

OBJECTIVE: To investigate expression and localization of the PROK ligands, receptors and their downstream transcriptional targets in the human fetal ovary.

SETTING: This study was conducted at the University of Edinburgh.

PARTICIPANTS: Ovaries were collected from 37 morphologically normal human fetuses.

DESIGN AND MAIN OUTCOME MEASURES: mRNA and protein expression of PROK ligands and receptors was determined in human fetal ovaries using qRT-PCR, immunoblotting and immunohistochemistry. Functional studies were performed using a human germ tumour cell line (TCam-2) stably transfected with PROKR1.

RESULTS: Expression of PROK1 and PROKR1 was significantly higher in mid-gestation ovaries (17-20 weeks) than at earlier gestations (8-11 and 14-16 weeks). PROK2 significantly increased across the gestations examined. PROKR2 expression remained unchanged. PROK ligand and receptor proteins were predominantly localised to germ cells (including oocytes within primordial follicles) and endothelial cells, indicating these cell types to be the targets of PROK signalling in the human fetal ovary. PROK1 treatment of a germ cell line stably-expressing PROKR1 resulted in ERK phosphorylation, and elevated COX2 expression.

CONCLUSIONS: Developmental changes in expression and regulation of COX2 and pERK by PROK1 suggest that PROK ligands may be novel regulators of germ cell development in the human fetal ovary, interacting within a network of growth and survival factors prior to primordial follicle formation.

Prostaglandin E2 as a regulator of germ cells during ovarian development

CONTEXT: The formation of primordial follicles occurs during fetal life yet is critical to the determination of adult female fertility. Prior to this stage, germ cells proliferate, enter meiosis, and associate with somatic cells. Growth and survival factors implicated in these processes include activin A (INHBA), the neurotrophins BDNF and NT4 (NTF5), and MCL1. The prostaglandins have pleiotrophic roles in reproduction, notably in ovulation and implantation, but there are no data regarding roles for prostaglandins in human fetal ovarian development.

OBJECTIVE: The aim of the study was to investigate a possible role for prostaglandin (PG) E(2) in human fetal ovary development.

DESIGN: In vitro analysis of ovarian development between 8 and 20 wk gestation was performed.

MAIN OUTCOME MEASURE(S): The expression patterns of PG synthesis enzymes and the PGE(2) receptors EP2 and EP4 in the ovary were assessed, and downstream effects of PGE(2) on gene expression were analyzed.

RESULTS: Ovarian germ cells express the PG synthetic enzymes COX2 and PTGES as well as the EP2 and EP4 receptors, whereas COX1 is expressed by ovarian somatic cells. Treatment in vitro with PGE(2) increased the expression of BDNF mRNA 1.7 +/- 0.16-fold (P = 0.004); INHBA mRNA, 2.1 +/- 0.51-fold (P = 0.04); and MCL1 mRNA, 1.15 +/- 0.06-fold (P = 0.04), but not that of OCT4, DAZL, VASA, NTF5, or SMAD3.

CONCLUSIONS: These data indicate novel roles for PGE(2) in the regulation of germ cell development in the human ovary and show that these effects may be mediated by the regulation of factors including BDNF, activin A, and MCL1.

Effects of vasectomy on spermatogenesis and fertility outcomes after assisted conception

Abstract BACKGROUND: Each year 40,000 men have a vasectomy in the UK whilst another 2400 request a reversal to begin a second family. Sperm can now be obtained by testicular biopsy and subsequently used in assisted conception with intracytoplasmic sperm injection (ICSI). The study aims were to compare sperm yields of men post-vasectomy or with obstructive azoospermia (OA) of unknown aetiology with fertile men and to assess any alteration in the clinical pregnancy rates after ICSI. METHODS: Testicular tissue was obtained by Trucut needle from men who had undergone a vasectomy >5yrs previously, had OA from other causes and from fertile men during vasectomy. Seminiferous tubules were milked to measure sperm yields. Numbers of Sertoli cells, spermatids and thickness of the seminiferous tubule walls were assessed using quantitative computerized analysis. RESULTS and CONCLUSIONS: Sperm yields/g testis were significantly decreased in men post-vasectomy and in men with OA, relative to fertile men. Significant reductions were also observed in early (40%) and mature (29%) spermatid numbers and an increase of 31% was seen in the seminiferous tubule wall (basal membrane and collagen thickness) of vasectomised men compared to fertile men. Clinical pregnancy rates in couples who had had a vasectomy were also significantly reduced.

Female reproductive biology of two sympatric incirrate octopod species, Adelieledone polymorpha (Robson 1930) and Pareledone turqueti (Joubin 1905) (Cephalopoda : Octopodidae), from South Georgia

The reproductive biology of two species of endemic Southern Ocean octopods was investigated around the sub-Antarctic islands of South Georgia and Shag Rocks. The females of both the species produce few, large eggs. This appears to be governed by phylogenetic constraint. No evidence was found for ontogenetic migration or seasonality associated with gonad maturation. Based on oocyte length frequency distributions and observations of oocyte development within the ovary, it is possible that both species could have either a single or multiple-batch spawning strategy. Pareledone turqueti ovaries contained fewer larger oocytes than those of Adefieledone polymorpha, which may help to reduce competition for resources immediately after hatching.