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Maternal malnutrition has important developmental consequences for the foetus. Indeed, adverse fetal ovarian development could have lifelong impact, with potentially reduced ovarian reserve and fertility of the offspring. This study investigated the effect of maternal protein restriction on germ cell and blood vessel development in the fetal sheep ovary. Ewes were fed control (n = 7) or low protein (n = 8) diets (17.0 g vs 8.7 g crude protein/MJ metabolizable energy) from conception to day 65 of gestation (gd65). On gd65, fetal ovaries were subjected to histological and immunohistochemical analysis to quantify germ cells (OCT4, VASA, DAZL), proliferation (Ki67), apoptosis (caspase 3) and vascularisation (CD31). Protein restriction reduced the fetal ovary weight (P < 0.05) but had no effect on fetal weight (P > 0.05). The density of germ cells was unaffected by maternal diet (P > 0.05). In the ovarian cortex, OCT4+ve cells were more abundant than DAZL+ve (P < 0.001) and VASA+ve cells (P < 0.001). The numbers, density and estimated total weight of OCT4, DAZL, and VASA+ve cells within the ovigerous cords were similar in both dietary groups (P > 0.05). Similarly, maternal protein restriction had no effect on germ cell proliferation or apoptotic indices (P > 0.05) and the number, area and perimeter of medullary blood vessels and degree of microvascularisation in the cortex (P > 0.05). In conclusion, maternal protein restriction decreased ovarian weight despite not affecting germ cell developmental progress, proliferation, apoptosis, or ovarian vascularity. This suggests that reduced maternal protein has the potential to regulate ovarian development in the offspring.

Lay summary

Variations in a mother’s diet during pregnancy can influence her offspring’s growth and might cause fertility problems in the offspring in later life. We investigated whether reducing the protein fed to sheep during early pregnancy affects their daughters’ ovaries. We then compared our findings to the offspring of sheep on a complete diet. We measured ovary size and estimated the number of germ cells (cells that become eggs) they contained. We used cell markers to assess potential changes in the pattern of germ cell growth, division, and death, and how the ovarian blood supply had developed. We found that protein restriction reduced ovary size. However, the pattern of germ cell development, growth, or death was not altered by poor diet and blood vessels were also unaffected. This suggests that maternal diet can change ovarian development by an unknown mechanism and might reduce future fertility in their offspring.

The Ubiquitous Transcribed Y (UTY a.k.a. KDM6C) AZFa candidate gene on the human Y chromosome and its paralog on the X chromosome, UTX (a.k.a. KDM6A), encode a histone lysine demethylase removing chromatin H3K27 methylation marks at genes transcriptional start sites for activation. Both proteins harbour the conserved Jumonji C (JmjC) domain, functional in chromatin metabolism, and an extended N-terminal tetratricopeptide repeat (TPR) block involved in specific protein interactions. Specific antisera for human UTY and UTX proteins were developed to distinguish the expression of both proteins in human germ cells by immunohistochemical experiments on appropriate tissue sections. In the male germ line, UTY was expressed in the fraction of A spermatogonia located at the basal membrane, probably including spermatogonia stem cells. UTX expression was more spread in all spermatogonia and in early spermatids. In female germ line, UTX expression was found in the primordial germ cells of the ovary. UTY was also expressed during fetal male germ cell development, whereas UTX expression was visible only at distinct gestation weeks. Based on these results and the conserved neighboured location of UTY and DDX3Y in Yq11 found in mammals of distinct lineages, we conclude that UTY, such as DDX3Y, is part of the Azoospermia factor a (AZFa) locus functioning in human spermatogonia to support the balance of their proliferation-differentiation rate before meiosis. Comparable UTY and DDX3Y expression was also found in gonadoblastoma and dysgerminoma cells found in germ cell nests of the dysgenetic gonads of individuals with disorders of sexual development and a Y chromosome in karyotype (DSD-XY). This confirms that AZFa overlaps with GBY, the Gonadoblastoma susceptibility Y locus, and includes the UTY gene.

Lay Summary

AZFa Y genes are involved in human male germ cells development and support gonadoblastoma (germ cell tumour precursor cells) in the aberrant germ cells of the gonads of females with genetic disorders of sexual development. The AZFa UTY gene on the male Y chromosome is equivalent to UTX on the female X chromosome. These genes are involved in removing gene regulators to enable activation of other genes (i.e. removal of histone methylation known as epigenetic modifications). We wanted to learn the function of UTY and UTX in developing sperm and eggs in human tissues and developed specific antibodies to detect both proteins made by these genes. Both UTY and UTX proteins were detected in adult and fetal sperm precursor cells (spermatogonia). UTX was detected in egg precursor cells (primordial germ cells). UTY was detected in gonadoblastoma and dysgerminoma tumour cells (germ cell tumours originating from genetic disorders of sexual development due to having a Y chromosome). Based on our study, we conclude that UTY is not only part of AZFa, but also of GBY the overlapping gonadoblastoma susceptibility Y region.

The boundaries of what we are able to do using ARTs are fast moving. In both human and veterinary medicine this presents a fundamental question: ‘Just because we can, should we?’ Or, to rephrase the same question: ‘How can we distinguish between what is a use and a misuse of an ART, across species?’ This paper assesses the scientific evidence base for and against the use of ARTs, and offers a personal opinion on how we can use such evidence to inform an ethical distinction between justifiable and unjustifiable uses of the techniques. It is argued that the law provides a necessary but insufficient basis for such distinctions. Based in evidence about harms and benefits, ARTs may be classified into three groups: those which should be rarely used; those for which current evidence supports arguments both for and against their use; and those which there is an ethical imperative to use. Which category a particular ART falls into varies depending upon the species to which it is being applied and the reason we are using it. In order to ensure that our ethical oversight keeps up with our technical prowess, the medical and veterinary professions should keep discussing and debating the moral basis of the use of ARTs, not only with each other but also with the lay public.

Controversy exists regarding the benefits of intravenous intralipid therapy in patients with poor reproductive history. It is frequently reported that there is no evidence to support the effectiveness, utility or safety for this treatment. While individual studies may be perceived as weak, a systematic review and meta-analysis was performed to determine if there is any advantage to patients. PubMed, Embase and Scopus searches were performed with the target populations being either recurrent pregnancy loss (RPL), or recurrent implantation failure (RIF) undergoing assisted reproductive technology (ART) and receiving intralipid infusions. These cohorts were compared with either placebo, no intervention or alternative treatments. The most relevant outcome measures were considered to be clinical pregnancy rate (CPR), live birth rate (LBR), implantation rate (IR) and miscarriage rate (MR). Twelve studies encompassing 2,676 participants met the criteria for selection and were included and reviewed. Treatment of the target population with intralipid led to an improvement in IR (Odds Ratio (OR) 2.97, 2.05-4.29), pregnancy rate (OR 1.64, 1.31-2.04), and LBR (OR 2.36, 1.75-3.17), with a reduction in MR (OR 0.2, 0.14-0.30). Although intravenous intralipid is not recommended as a routine treatment for recurrent miscarriage or implantation failure, there is enough data to suggest consideration in selected patients where routine testing is unremarkable, standard treatments have failed and immunological risk factors are present. The presence of abnormal uterine natural killer (uNK) cells needs more study as a target marker to determine those who could benefit.

Graphical abstract

13-lined ground squirrels (TLGS; Ictidomys tridecemlineatus) are small, omnivorous, fossorial, hibernating sciurids. TLGS are seasonal induced ovulators, with a ~28-day gestation period. The main goal of this study was to ascertain whether enzyme-linked immunosorbent assay (ELISA) of TLGS fecal samples can be used to non-invasively detect pregnancy. Competitive ELISAs for progestogen metabolites were conducted on feces collected from a group of (n =13) females. Feces were collected thrice weekly during the breeding season and frozen for subsequent analysis. Competitive ELISAs were run using progesterone kits ), setting data against seven different time-points between hibernation, emergence, and litter birthdate. Eleven females produced litters. ELISA data from the (n = 2) non-pregnant females demonstrated no rise in progestogen metabolites at any point over 28 days. In contrast, data from the (n = 11) pregnant females all demonstrated a pronounced rise in progestogen metabolites, with most animals displaying progesterone withdrawal in the final week of gestation. A >20-fold rise in progestogen metabolite was observed halfway through gestation (P < 005). Analysis on litter size and progestogen metabolite concentration showed no significant correlation (r2 = −0.615). Initial correlation analysis done on sex ratio of litters vs progestogen metabolites showed no significant effect of progesterone on sex ratios (males: r2 = −0.772, females: r2 = 0.375). This work demonstrated that TLGS also undergo progesterone withdrawal about a week before parturition. We have ascertained that a commercially available progesterone assay kit can detect a significant elevation in progestogen metabolites in this species about halfway through gestation.

Lay summary

This research was conducted to discover whether pregnancy prediction is possible in female 13-lined ground squirrels (TLGS; a small hibernating ground squirrel named for their number of stripes). Pregnancy status in this species, we postulated, could be anticipated by generating profiles for individuals via a non-invasive technique known as fecal endocrine hormone profiling. Fecal samples were collected from 13 females thrice weekly for 4 weeks post-hibernation in the breeding season of 2016. Fecal samples were then processed and run through an assay known as an ELISA giving concentrations of hormone metabolites excreted through feces. We then set these samples against time points to develop a profile for each female. We have ascertained that elevated progesterone (potential pregnancy) can be detected by a commercially available assay kit. Understanding hormone patterns in animals gives researchers a better idea of best husbandry practices, including breeding in managed care.

October 22, 2020

New Editorial Board members


Reproduction and Fertility has two new members who have joined the Editorial Board, Dr Channa Jayasena and Dr Mehdi Ommati.


May 7, 2020

Reproduction and Fertility – now open for submissions


In partnership with Bioscientifica, the Society for Reproduction and Fertility is pleased to announce the launch of their new fully open-access, peer-reviewed journal, Reproduction and Fertility.

Led by Co-Editors-in-Chief Andrew Horne and Norah Spears, Reproduction and Fertility will see vigorous yet rapid peer review of the latest basic, translational and clinical research in the field.


May 7, 2020

Article Publication Charge waived


In celebration of the launch of Reproduction and Fertility, Bioscientifica and the Society for Reproduction and Fertility are sponsoring the Article Publication Charge during the launch years of the journal*.

*The Society for Reproduction and Fertility and Bioscientifica reserve the right to withdraw this offer at any time.