Endocrine disruptors, such as environmental compounds with endocrine-altering properties, may cause hypospadias and cryptorchidism in several species, including humans. Anogenital distance is sexually dimorphic in many mammals, with males having longer anogenital distance on average than females. Animal models of proposed endocrine disruptors have associated prenatal exposure with hypospadias, cryptorchidism, and reduced anogenital distance. Human studies have correlated shorter anogenital distance to in utero exposure to putative endocrine disruptors. We review preliminary data suggesting that anogenital distance is reduced in boys with hypospadia and cryptorchidism. Hence, human hypospadias and cryptorchidism may be associated with reduced anogenital distance as a result of endocrine disruption.

Associations among hypospadias, cryptorchidism, anogenital distance, and endocrine disruption

Effects of Equex, one- or two-step dilution, and two freezing and thawing rates on post-thaw survival of dog spermatozoa.

This paper resulted from a conference entitled “Lactation and Milk: Defining and refining the critical questions” held at the University of Colorado School of Medicine from January 18–20, 2012. The mission of the conference was to identify unresolved questions and set future goals for research into human milk composition, mammary development and lactation. We first outline the unanswered questions regarding the composition of human milk (Section I) and the mechanisms by which milk components affect neonatal development, growth and health and recommend models for future research. Emerging questions about how milk components affect cognitive development and behavioral phenotype of the offspring are presented in Section II. In Section III we outline the important unanswered questions about regulation of mammary gland development, the heritability of defects, the effects of maternal nutrition, disease, metabolic status, and therapeutic drugs upon the subsequent lactation. Questions surrounding breastfeeding practice are also highlighted. In Section IV we describe the specific nutritional challenges faced by three different populations, namely preterm infants, infants born to obese mothers who may or may not have gestational diabetes, and infants born to undernourished mothers. The recognition that multidisciplinary training is critical to advancing the field led us to formulate specific training recommendations in Section V. Our recommendations for research emphasis are summarized in Section VI. In sum, we present a roadmap for multidisciplinary research into all aspects of human lactation, milk and its role in infant nutrition for the next decade and beyond.

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Lactation and Neonatal Nutrition: Defining and Refining the Critical Questions

Mucometra, cystic endometrial hyperplasia, and pyometra in the bitch: advances in treatment and assessment of future reproductive success.

In dogs, the termination of the 3-10-month obligate anoestrus involves selection of a cohort of LH-sensitive follicles, presumably from a wave of dominant small antral follicles that would otherwise undergo atresia. The number and size of such follicles appears to increase, especially during the last 50 days of anoestrus when the already elevated concentrations of FSH become further elevated. The final selection and eventual terminal development of these follicles is caused by an increased frequency of high-amplitude LH pulses at the end of anoestrus. Concomitant increases in FSH are typically small or negligible. High concentrations of FSH in anoestrus are likely to be important in maintaining, if not stimulating, overlapping waves of dominant follicles throughout anoestrus, their expression of aromatase activity and basal oestradiol secretion sufficient to suppress LH by negative feedback. An attractive hypothesis is that late anoestrus increases in LH-stimulate synthesis of precursor androgen for already available FSH-dependent aromatase. After 7 or more days of elevated LH, and perhaps 2-5 days of semi-autonomous growth, with maximal oestradiol production reached, follicle capacity to further increase oestradiol becomes limited and excess progesterone becomes increasingly secreted. The pre-ovulatory LH surge and oestrus onset are then triggered - often synchronously and in concert with the terminal maturation of the follicles - by central effects of the large decrease in the oestrogen to progestin ratio. Follicular endocrine and paracrine events during and following the LH surge are likely similar to those reported for other species. The prolonged luteal phase lengths of 55-75 days in non-pregnant bitches bracket the 64 +/- 1 day in pregnancy and represent a genetically programmed luteal cell lifespan approximating gestation length as occurs in the luteal phase of hysterectomized animals of most polyoestrous artiodactyls and rodents. The 30-40-day slow regression after day 20 to 30 involves periodic cell death, diminution in cell size, low levels of apoptosis and minimal or modest involvement of endogenous prostaglandin F (PGF) production. The canine corpus luteum (CL) is dependent on both LH and prolactin as stimulating luteotrophins by day 15, and as required luteotrophins by days 20-25, if not earlier. Thereafter, both luteotrophins likely have cellular mechanisms of action similar to those reported for other species. Progesterone secretion during pregnancy is greatly enhanced by characteristic, and probably relaxin-stimulated, increases in prolactin concentration starting at or after day 25, and persisting to term. Near term, foetoplacental maturation results in the placental release of large, luteolytic amounts of PGF for 1-2 days pre-partum. Pre-partum luteolysis, like that induced by exogenous prostaglandin, likely involves a cascade enhanced by the removal of progesterone inhibition of PGF release and some degree of intra-luteal PGF synthesis. That a likely twofold or greater increase in progesterone production by the CL of pregnancy does not result in significantly higher serum progesterone than in non-pregnant metoestrus relates to several biological changes, including a large increase in plasma volume of distribution, increased metabolism of progesterone by increased uterine, placental and mammary masses and increased liver clearance and excretion of progesterone and progesterone metabolite. Anoestrus length and ovarian cycle intervals, variable within and among bitches, are likely affected by neuroendocrine components of an endogenous circannual cycle, albeit only photo-entrained in the Basenji breed. This may be modified by the prior luteal phase, exposure to oestrus female pheromones and as yet unknown mechanisms that likely operate via inhibitory opioidergic and/or stimulatory dopaminergic hypothalamic pathways affecting late anoestrus increases in LH.

Endocrinologic control of normal canine ovarian function.

Cryosurvival of Dog Spermatozoa at Different Glycerol Concentrations and Freezing/Thawing Rates

This study was conducted to evaluate clinical efficacy of deslorelin for inhibiting reproduction in the bitch. Ten adult healthy bitches or bitches with mammary neoplasia for which owners were requesting suppression of cyclicity without performing gonadectomy were administered a 4.7- or a 9.4-mg deslorelin implant subcutaneously. The first implant of deslorelin was administered in anoestrus (n = 5) or in dioestrus (n = 5). Treatment was repeated every 5 months for as long as necessary based on the clinical situation of the dog and owner's desires. Some of the bitches implanted in anoestrus came in heat within 4-15 days after treatment, while none of the bitches implanted in dioestrus showed heat during treatment. Suppression of reproductive cyclicity was successfully achieved in 6/10 bitches for 1-4 years. No behavioural and local/general side-effects were observed in any of the treated bitches. The 4.7-mg deslorelin implant may work well for suppression of cyclicity provided that it is administered in dioestrus and at intervals of 4.5 months. A 9.4-mg implant may be more suitable for this use although its efficacy may also be shorter than 12 months. Owner compliance is an important limiting factor.

Clinical use of deslorelin for the control of reproduction in the bitch.

As in all domestic mammals, sexual differentiation in dogs and cats starts early in the embryonic period prenatally and continues into early postnatal life. The result of such a process is, however, not evident until after puberty,a time when the entire reproductive system undergoes significant changes. Normality of sexual differentiation is difficult to observe in neonates of small animals, with the only gender difference being a slightly longer anogenital distance in male (13-15 mm) versus female (7-8 mm)animals. Early diagnosis of deviations from normality can spare breeders the time and effort devoted to raising an animal that may turn out to be unsuitable for becoming part of the reproductive stock and may spare owners the concern for a pet whose health may be unnecessarily threatened by failing to remove a malformed reproductive system early in life. This article reviews the incidence, clinical and gross anatomic features,and diagnostic approaches that veterinarians can use to address inborn errors of the reproductive system of dogs and cats, highlighting those malformations that bear clinical relevance and may become manifest from birth until puberty.

Disorders of Sexual Differentiation in Puppies and Kittens: A Diagnostic and Clinical Approach

Records of elective abortion in 27 bitches presented to the Veterinary Surgery and Reproduction Clinic of the University of Pisa were reviewed. Treatment consisted of twice-daily subcutaneous injections of 150-270 micrograms natural prostaglandin F2 alpha kg-1 for 4 consecutive days starting between cytological dioestrous days 5 and 19. None of the treated bitches whelped. Luteolysis appeared to be complete (serum progesterone < 3.2 nmol l-1) at the end of treatment in 22 of 25 bitches in which progesterone was assayed in serum obtained daily during therapy. Serum progesterone rose after treatment to a concentration consistent with pregnancy in four of 17 bitches in which progesterone was measured once between dioestrous days 23 and 51. The mean intercycle interval (pro-oestrus-pro-oestrus) of the cycle in which abortion was induced was 134 +/- 45 days for 15 dogs for which the interval could be determined, and was significantly shorter than the average preceding interoestrous intervals (210 +/- 40.0 days) for the same dogs (P < 0.001).

Clinical use of prostaglandin F2 alpha to induce early abortion in bitches: serum progesterone, treatment outcome and interval to subsequent oestrus.

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The purpose of this study was to define (i) the interval between treatment and sterility, and (ii) semen quality in male dogs administered a 4.7-mg deslorelin implant. Six healthy, adult dogs of various breeds and body weights were implanted with deslorelin (Suprelorin, Virbac) and followed every 2 weeks with semen and blood collections. Semen quality remained stable or even improved during the first month following treatment and then showed a progressive decline until the end of the study, except for sperm morphology, which was unaffected by the treatment. Complete sterility was achieved on post-treatment days 70, 84, 60, 23, 51 and 40 for dogs 1 to 6, respectively. The 4.7 mg deslorelin implant caused a significant (p < 0.05) decrease in serum testosterone as well as sperm motility. Our results (i) confirm the efficacy of deslorelin in causing reversible sterility in male dogs, (ii) confirm and provide details about endocrine and seminal parameters involved in this process and (iii) contribute to define the interval between treatment and achievement of complete sterility. Practitioners should be aware that such interval may be longer than 2 months in some cases, and that fertility may actually be increased during the first 2–4 weeks post-treatment.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/rda.12058

Stefano Romagnoli

Papers

Cryosurvival of Dog Spermatozoa at Different Glycerol Concentrations and Freezing/Thawing Rates

Clinical use of deslorelin for the control of reproduction in the bitch.

Disorders of Sexual Differentiation in Puppies and Kittens: A Diagnostic and Clinical Approach

Clinical use of prostaglandin F2 alpha to induce early abortion in bitches: serum progesterone, treatment outcome and interval to subsequent oestrus.

Semen quality and onset of sterility following administration of a 4.7-mg deslorelin implant in adult male dogs.